Asymmetric cyclopropanation of olefins catalysed by Cu(I ... · -mail: [email protected]...

Supporting Information Asymmetric cyclopropanation of olefins catalysed by Cu(I) complexes

of chiral pyridine-containing macrocyclic ligands (Pc-L*)

Brunilde Castanoa, Stefano Guidone,

a,e Emma Gallo,

a Fabio Ragaini,

a Nicola Casati,

b Piero

Macchi,c Massimo Sisti

d and Alessandro Caselli*

a

a Dipartimento di Chimica, Università di Milano, and ISTM-CNR; Via Golgi 21, 20133 Milano, Italy. Fax: (+39)02

5031 4405; Tel: (+39)02 5031 4372; E-mail: [email protected] b Laboratory for Synchrotron Radiation - Condensed Matter, Swiss Light Source, Paul Scherrer Institut,Villigen PSI

CH-5232 Villigen Switzerland. c Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH3012, Bern, Switzerland. d Dip. Scienza e Alta Tecnologia, Università degli Studi dell’Insubria, Via Valleggio 11, 22100 Como, Italy. e Present address: EaStCHEM School of Chemistry, University of St Andrews, St Andrews, UK, KY16 9ST

General. NMR spectra were recorded on Bruker Avance 300-DRX or Avance 400-DRX

spectrometers. Chemical shifts (ppm) are reported relative to TMS. The 1H NMR signals of the

compounds described in the following have been attributed by COSY and NOESY techniques.

Assignments of the resonance in 13

C NMR were made using the APT pulse sequence and HSQC

and HMBC techniques. The 15

N NMR signals of the compound described have been attributed by

HMBC technique. Infrared spectra were recorded on a BIO-RAD FTS-7 spectrophotometer.

Elemental analyses and mass spectra were recorded in the analytical laboratories of Milan

University. GC-MS analysis were performed on a Shimadzu GCMS-QP5050A instrument. Optical

rotation were measured on a Perkin Elmer instruments model 343 plus; []D values are given in

10-1

deg cm2 g

–1. Microwave assisted reactions were performed with a MILESTONE® microSYNT

multimode labstation, using 12 mL sealed glass vessels. The internal temperature was detected with

a fiber optic sensor. Unless otherwise specified, all the reactions were carried out in a dinitrogen

atmosphere employing standard Schlenk techniques and magnetic stirring. Solvents were dried

prior use by standard procedures and stored under dinitrogen. -Methylstyrene was distilled over

CaH2 and stored under dinitrogen. Copper(I) triflate benzene complex, copper(I) tetrakis-

acetonitrile esafluorophosphate complex and copper(I) tetrakis-acetonitrile tetrafluoro borate

1

Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012

mailto:[email protected]

complex were synthesized following literature methods.1 All other starting materials were

commercial products and were used as received. The synthesis and characterization of

bis(sulfonamides) 3a, the macrocycles 4a and the copper(I) complexes 6a were already reported.2

The synthesis and characterization of bis(sulfonamides) 3c-d, the macrocycles 4c-d and the

copper(I) complexes 6c-d, 8d-10d were reported in a previous communication.3 The collected

analytical data for cis and trans ethyl-2-methyl-2-phenylcyclopropanecarboxylate,4, cis and trans

tert-butyl 2-methyl-2-phenylcyclopropanecarboxylate,5 cis and trans ethyl-2-

phenylcyclopropanecarboxylate,6 cis and trans ethyl-2-p-tolyl-cyclopropanecarboxylate,

7 cis and

trans ethyl 2-(4-chlorophenyl)cyclopropanecarboxylate,7 ethyl-2,2-

diphenylcyclopropanecarboxylate,6 cis and trans ethyl 2,2-dimethyl-3-(2-

methylpropenyl)cyclopropanecarboxylate (ethyl chrysanthemate),5 dimethyl-2-

oxabicyclo[3.1.0]hex-3-ene-3,6-dicarboxylate8 and cis and trans ethyl-2-

hexylcyclopropanecarboxylate9 are in agreement with those reported in the literature.

Synthesis of 3b

NTs

NH2+toluene

reflux

NHN

Ts

HN

Ts

3b1a

This synthesis can be performed in the air. A solution of 1-tosylaziridine 1a (2.24 g, 11.5 mmol)

and 1-naphthylmethylamine (0.811 g, 5.16 mmol) in distilled toluene (11 mL) was stirred and

heated under reflux for 5 h. The mixture was dried and purified by silica gel chromatography using

n-hexane:ethyl acetate = 6:4 as eluant, obtaining pure amine 3b (2.14 g, 5.04 mmol, yield: 75%).

NHN

SO2

HN

Ts

3b

a

b

c

d

e

f

g

h

i

l

m

n

op

1

2

3 4

2


1H NMR (300 MHz; CDCl3; T = 300 k) δ 8.14 (1H, d, J = 8.3 Hz, H

i), 7.86 (1H, d, J = 8.3 Hz,

ArH), 7.78 (1H, m, ArH), 7.54 (4H, d, J = 8.0 Hz, Hn) overlapping with 7.61-7.49 (2H, m, ArH),

7.42-7.32 (2H, m, ArH), 7.19 (4H, d, J = 8.0 Hz, Ho), 4.83 (2H, bs, NH), 4.00 (2H, br, CH2

3), 2.90

(4H, m, CH2), 2.66 (4H, m, CH2), 2.38 (6H, s, CH34).

13C NMR (75 MHz; CDCl3; T = 300 k) δ

143.5 (C), 136.7 (C), 134.0 (C), 132.0 (C), 129.8 (CH), 129.0 (C0H), 127.1 (C

nH), 126.3 (CH),

125.4 (CH), 123.7 (CiH), 54.2(CH2), 40.8 (C

3H2), 21.6 (C

4H3). Signals relative to quaternary

carbons, aromatic CH and CH2 were not detected. Elemental Analysis: Found: C, 63.1; H, 6.2; N,

7.5% Calc. for C29H33N3O4S2: C, 63.1; H, 6.0; N, 7.6%.

Synthesis of 2e-(2S) and 3e-(2S,2’S)

NTs

(S)

NH2+toluene

reflux

N

(S)

HN

Ts

(S)

HN

Ts

3e-(2S,2'S)

NH

(S)

HN

Ts+

2e-(2S)1b

This synthesis can be performed in the air. A solution of (S)-2-isopropyl-1-tosylaziridine 1b

(1.732 g, 7.23 mmol) and 1-naphthylmethylamine (0.494 g, 3.14 mmol) in distilled toluene (15 mL)

was stirred and heated under reflux for 5 h. The mixture was dried and purified by silica gel

chromatography using n-hexane:ethyl acetate = 7:3 as eluant, obtaining monoamine 2e-(2S) (0.875

g, 2.21 mmol, yield: 70%) and pure amine 3e-(2S,2’S) (0.600 g, 0.944 mmol, yield: 30%).

Synthesis of 3e-(2S,2’S) from 2e-(2S) under conventional heating

NTs

(S)

+

toluene

refluxN

(S)

HN

Ts

(S)

HN

Ts

3e-(2S,2'S)

NH

HN

Ts

2e-(2S)1b

A solution of (S)-2-isopropyl-1-tosylaziridine 1b (0.258 g, 1.08 mmol) and monoamine 2e-(2S)

(0.349 g, 0.88 mmol) in toluene (10 mL) was stirred and heated under reflux for 33 h. The mixture

3


was dried and purified by silica gel chromatography using n-hexane:ethyl acetate = 7:3 as eluant,

obtaining the amine 3e-(2S,2’S) (0.330 g, 0.519 mmol, yield: 74%).

SO2

a

b

c

d

e

f

g

h

i

l m

n

op

12

34 5

6

7

NH

HN

2e-(2S) 1H NMR (300 MHz; CDCl3; T = 300 k) δ 8.02 (1H, dd, J = 7.7 Hz, J = 1.3 Hz, H

i), 7.89 (1H, dd,

J = 7.7 Hz, J = 1.3 Hz, Hf), 7.81 (1H, dd, J = 7.7 Hz, J = 1.3 Hz, H

d), 7.62 (2H, d, J = 7.9 Hz, H

n),

7.55 (1H, t, J = 7.7 Hz, Hg), 7.54 (1H, t, J = 7.7 Hz, H

h), 7.42 (1H, t, J = 7.7 Hz, H

c), 7.38 (1H, d, J

= 7.7 Hz, Hb), 7.08 (2H, d, J = 7.9 Hz, H

o), 4.14 (1H, d, J = 13.4 Hz, H

6), 4.08 (1H, d, J = 13.4 Hz,

H6’

), 3.09 (1H, ddd, J = 6.8 Hz, J = 6.8 Hz, J = 4.4 Hz, H2), 2.73 (1H, dd, J = 12.4 Hz, J = 6.8 Hz,

H1’

), 2.60 (1H, dd, J = 12.4 Hz, J = 4.4 Hz, H1), 2.29 (3H, s, CH3

7), 1.85 (1H, m, H

3), 0.81 (3H, d, J

= 6.81 Hz, CH34), 0.79 (3H, d, J = 6.81 Hz, CH3

5). The signals relative to NH were not detected.

13C NMR (75 MHz; CDCl3; T = 300 k) δ 129.6 (C

nH), 129.0 (C

fH), 128.5 (C

dH), 127.2 (C

oH),

126.7 (CH), 126.6 (CH), 126.1 (CH), 125.5 (CH), 123.6 (CiH), 58.2 (C

2H), 50.9 (C

6H2), 49.0

(C1H2), 30.5 (C

3H), 21.5 (C

7H3), 18.9 (C

4H3), 18.4 (C

5H3). The signals relative to quaternary

carbons were not detected. Elemental Analysis: Found: C, 69.8; H, 7.0; N, 6.9% Calc. for

C23H28N2O2S: C, 69.7; H, 7.1; N, 7.1%. MS (EI): m/z 397 (M++1). []D

20 = - 3.611° (c 1.082 in

CHCl3).

NHN

SO2

HN

Ts

3e-(2S,2'S)

a

b

c

d

e

f

g

h

i

l

m

n

op

1 2

34

5

6 7


i), 7.85-7.76 (2H, m, H

d and

Hf), 7.75 (4H, d, J = 8.2 Hz, H

n), 7.51-7.38 ( 3H, m, H

c, H

h and H

g), 7.34 (1H, d, J = 8.0 Hz, H

b),

7.23 (4H, d, J = 8.2 Hz, Ho), 4.99 (2H, d, J = 6.0 Hz, NH), 4.04 (1H, d, J = 13.1, H

6), 3.80 (1H, d, J

= 13.1 Hz, H6’

), 3.45 (2H, m, H2), 2.55-2.35 (4H, m, H

1), overlapping with 2.38 (6H, s, CH3

7), 1.79

4


(2H, m, H3), 0.53 (6H, d, J = 6.9 Hz, CH3

4), 0.52 (6H, J = 6.9 Hz, CH3

5).

13C NMR (75 MHz;

CDCl3; T = 300 k) δ 143.2 (C), 138.6 (C), 133.9 (C), 132.2 (C), 129.6 (CnH), 128.6 (CH), 128.2

(CH), 127.1 (CoH), 126.3 (CH), 125.8 (CH), 125.3 (CH), 124.3 (C

iH), 56.9 (C

6H2), 55.9 (C

2H),

54.9 (C1H2), 29.3 (C

3H), 21.6 (C

7H3), 17.9 (C

4H3), 16.9 (C

5H3). A signal relative to a quaternary

carbon was not detected. Elemental Analysis: Found: C, 66.3; H, 7.2; N, 6.3% Calc. for

C35H45N3O4S2: C, 66.1; H, 7.1; N, 6.6%. MS (EI): m/z 636 (M++1). []D

20 = + 9.92 (c 1.31 in

CHCl3).

Synthesis of 2f-(1R,2S) under microwave heating

NTs

(S)

NH2(R)

+toluene

MW

NH

(R)(S)

HN

Ts

2f-(1R,2S)1b


(0.811 g, 3.39 mmol) and (R)-1-(1-naphthyl)ethyl amine (0.529 g, 3.09 mmol) in toluene (21 mL)

was added in a microwave tube. The solution was stirred and heated by microwave irradiation for 3

h at 150 °C. The resulting mixture was dried and purified by silica gel chromatography using n-

hexane:ethyl acetate = 7:3 as eluant, obtaining a yellow solid 2f-(1R,2S) (0.904 g, 2.20 mmol, yield:

71%).

SO2

a

b

c

d

e

f

g

h

i

l m

n

op

12

34 5

6

7

NH

HN

2f-(1R,2S)

8

1H NMR (300 MHz; CDCl3; T = 300 k) δ 8.03 (1H, m, H

i), 7.89 (1H, m, ArH), 7.78 (2H, d, J =

8.4 Hz, Hn) overlapping with 7.79-7.75 (1H, m, ArH) 7.52-7.45 (4H, m, ArH), 7.25 (2H, d, J = 8.4

Hz, Ho), 5.22 (1H, br, NH), 4.35 (1H, q, J = 6.6 Hz, H

6), 3.08 (1H, m, H

2), 2.46-2.42 (2H, m, H

1),

2.40 (3H, s, CH38), 1.85 (1H, dh, J = 13.4 Hz, J = 6.8 Hz, H

3), 1.36 (3H, d, J = 6.6 Hz, CH3

7), 0.81

(3H, d, J = 6.8 Hz, CH34), 0.78 (3H, d, J = 6.8 Hz, CH3

5) One NH signal is too broad to be detected.

5


13C NMR (75 MHz; CDCl3; T = 300 k) δ 143.2 (C), 140.8 (C), 138.2 (C), 134.1 (C),131.3 (C),129.6

(CoH), 129.1 (CH),127.4 (CH), 127.2 (CH), 125.9 (CH), 125.7 (CH), 125.5 (CH), 122.8

(CiH),122.6 (CH), 59.0 (C

2H), 53.3 (C

6H), 47.4 (C

1H2), 30.4 (C

3H), 23.5 (C

7H3), 21.5 (C

8H3), 18.8

(C4H3), 18.4 (C

5H3).

15N NMR (40 MHz; CDCl3; T = 300 k) δ 98.0 (NHTs), 40.1 (NHC

6).

Elemental Analysis: Found: C, 70.4; H, 7.4; N, 6.6% Calc. for C24H30N2O2S: C, 70.2; H, 7.4; N,

6.8%. []D20

= + 9.92 (c 1.31 in CHCl3).

Synthesis of 3f-(1R,2S,2’S) from 2f-(1R,2S) under conventional heating

NTs

(S)

+toluene

refluxN(R)

(S)

HN

Ts

(S)

HN

Ts

3f-(1R,2S,2'S)

NH

(R)(S)

HN

Ts

1b 2f-(1R,2S)

A solution of (S)-2-isopropyl-1-tosylaziridine 1b (0.307 g, 1.28 mmol) and monoamine 2f-

(1R,2S) (0.478 g, 1.16 mmol) in toluene (10 mL) was stirred and heated under reflux for 90 h. The

mixture was dried and purified by silica gel chromatography using n-hexane:ethyl acetate = 7:3 as

eluant, obtaining a yellow solid 3f-(1R,2S,2’S) (0.302 g, 0.464 mmol, yield: 40%).

Direct synthesis of 3f-(1R,2S,2’S)

NTs

(S)

NH2(R)

+toluene

MW

NH

(R)(S)

HN

Ts

2f-(1R,2S)1b

NTs

(S)

+

1b

toluene

refluxN(R)

(S)

HN

Ts

(S)

HN

Ts

3f-(1R,2S,2'S)

A solution of (S)-2-isopropyl-1-tosylaziridine 1b (0.781 g, 3.21 mmol) and (R)-1-(1-

naphthyl)ethyl amine (0.514 g, 3.0 mmol) in toluene (21 mL) was added in a microwave tube. The

solution was stirred and heated by microwave irradiation for 3h at 150°C. The resulting mixture,

without any purification, was added to a solution of (S)-2-isopropyl-1-tosylaziridine 1b (0.785 g,

3.28 mmol) in distilled toluene (4 mL) and was stirred and heated under reflux for 45 h. The

6


mixture was dried and purified by silica gel chromatography using n-hexane:ethyl acetate = 7:3 as

eluant, obtaining a yellow solid 3f-(1R,2S,2’S) (0.785 g, 1.21 mmol, yield: 40%).

NHN

SO2

HN

Ts

3f-(1R,2S,2'S)

a

b

c

d

e

f

g

h

i

l

m

n

op

1 2

34

5

68

7


i) 7.79(4H, d, J = 8.0 Hz, H

n)

overlapping with 7.79 (1H, m, ArH), 7.73 (1H, dd, J = 5.8 Hz, J = 3.4 Hz, ArH), 7.45-7.42 (2H, m,

ArH), 7.40-7.39 (2H, m, ArH), 7.29 (4H, d, J = 8.0 Hz, Ho), 4.66 (2H, d, J = 7.9 Hz, NH), 4.59 (1H,

q, J = 6.6 Hz, H6), 3.26 (1H, m, H

2), 2.46 (2H, dd, J = 13.4 Hz, J = 5.1 Hz, H

1), 2.41 (6H, s, CH3

8),

1.55 (2H, m, H3), 1.20 (3H, d, J = 6.6 Hz, CH3

7) 0.56 (6H, d, J = 6.9 Hz, CH3

4), 0.19 (6H, d, J = 6.8

Hz, CH35).

13C NMR (75 MHz; CDCl3; T = 300 k) δ 143.4 (C), 138.2 (C), 138.0 (C), 134.1 (C),

132.1 (C), 129.7 (CnH), 128.8 (CH), 128.2 (CH), 127.3 (C

oH), 125.6 (CH), 125.5 (CH), 125.1 (CH),

125.0 (CH), 123.9 (CH), 56.6 (C2H), 53.6 (C

6H), 52.3 (C

1H2), 27.6 (C

3H), 21.6 (C

8H3), 19.3

(C4H3), 14.8 (C

5H3), 12.4 (C

7H3).

15N NMR (40 MHz; CDCl3; T = 300 k) δ 94.0 (NHTs), 38.3

(NHC6). Elemental Analysis: Found: C, 66.6; H, 7.6; N, 6.5% Calc. for C36H47N3O4S2: C, 66.5; H,

7.3; N, 6.5%. []D20

= - 47.22 (c 1.37 in CHCl3).

Synthesis of 2g-(1S,2S) and 3g-(1S,2S, 2’S)

NTs

(S)

NH2(S)

+toluene

reflux

N(S)

(S)

HN

Ts

(S)

HN

Ts

3g-(1S,2S,2'S)

NH

(S)(S)

HN

Ts+

2g-(1S,2S)1b


(2.080 g, 8.7 mmol) and (S)-1-(1-naphthyl)ethyl amine (0.498 g, 2.90 mmol) in distilled toluene

(38 mL) was stirred and heated under reflux for 220 h. The mixture was dried and purified by silica

gel chromatography using n-hexane:ethyl acetate = 7:3 as eluant, obtaining monoamine 2g-(1S,2S)

(0.686 g, 1.67 mmol, yield: 58%) and pure amine 3g-(1S,2S, 2’S) (0.754 g, 1.16 mmol, yield: 40%).

7


SO2

a

b

c

d

e

f

g

h

i

l m

n

op

12

34 5

6

7

NH

HN

2g-(1S,2S)

8

1H NMR (300 MHz; CDCl3; T = 300 k) δ 8.15 (1 H, m, ArH), 7.90 (1H, m, ArH), 7.78 (1H, dd, J

= 7.9 Hz, J = 1.8 Hz, ArH), 7.55-7.43 (6H, m, ArH), 6.96 (2H, d, J = 7.9 Hz, ArH), 5.09 (1H, bs,

NH), 4.38 (1H, q, J = 6.5 Hz, H6), 2.92 (1H, m, H

2), 2.59 (1H, dd, , J = 12.3 Hz, J = 5.5 Hz, H

1),

2.26 (3H, s, CH38), 2.19 (1H, dd, J = 12.3 Hz, J = 4.5 Hz, H

1’), 1.84 (1H, m, H

3), 1.40 (3H, d, J =

6.5 Hz, CH37), 0.88 (3H, d, J = 6.8 Hz, CH3

4), 0.83 (3H, d, J = 6.8 Hz, CH3

5).

13C NMR (75 MHz;

CDCl3; T = 300 k) δ 142.9 (C), 140.9 (C), 137.7 (C), 134.2 (C), 131.4 (C), 129.4 (CH), 129.1 (CH),

127.5 (CH), 127.0 (CH), 125.9 (CH), 125.8 (CH), 125.6 (CH), 123.3 (CH), 123.1 (CH), 59.3 (C2H),

54.5 (C6H), 48.0 (C

1H2), 30.3 (C

3H), 23.7 (C

7H3), 21.4 (C

8H3), 19.0 (C

4H3), 18.8 (C

5H3). Elemental

Analysis: Found: C, 70.3; H, 7.5; N, 6.7% Calc. for C24H30N2O2S: C, 70.2; H, 7.4; N, 6.8%. []D20

= - 45.09 (c 1.02 in CHCl3).

NHN

SO2

HN

Ts

3g-(1S,2S,2'S)

a

b

c

d

e

f

g

h

i

l

m

n

op

1 2

34

5

68

7


i), 7.73 (2H, d, J = 7.8 Hz,

ArH), 7.70 (4H, d, J = 8.3 Hz, Hn), 7.56 (1H, pt, J = 8.2 Hz, ArH), 7.43-7.37 (2H, m, ArH), 7.29

(1H, m, ArH), 7.24 (4H, d, J = 8.3 Hz, Ho), 5.36 (2H, d, J = 5.4 Hz, NH), 5.13 (1H, q, J = 6.5 Hz,

H6), 3.68 (2H, m, H

2), 2.48-2.42 (4H, m, H

1), overlapping with 2.42 (6H, s, CH3

8), 1.76 (2H, m,

H3), 1.48 (3H, d, J = 6.5 Hz, CH3

7), 0.68 (6H, d, J = 7.0 Hz, CH3

4), 0.35 (6H, d, J = 7.0 Hz, CH3

5)

13C NMR (75 MHz; CDCl3; T = 300 k) δ 143.0 (C

p), 139.3 (C), 137.9 (C), 134.1 (C), 131.7 (C),

129.5 (CnH), 128.4 (CH), 127.4 (CH), 127.1 (C

oH), 125.9 (CH), 125.2 (CH), 124.9 (CH), 124.6

(CH), 54.7 (C2H), 53.3 (C

6H), 48.1 (C

1H2), 29.6 (C

3H), 21.7 (C

8H3), 18.0 (C

4H3), 15.9 (C

5H3), 11.1

(C7H3). A signal relative to an aromatic carbon was not detected. Elemental Analysis: Found: C,

8


66.4; H, 7.3; N, 6.7% Calc. for C36H47N3O4S2: C, 66.5; H, 7.3; N, 6.5%. MS (EI): m/z 650 (M++1).

[]D20

= - 33.65 (c 0.28 in CHCl3).

Direct synthesis of 2h-(2S) and 3h-(2S,2’S)

NTf

(S)

NH2

N

(S)

HN

Tf

(S)

HN

Tf

3h-(2S,2'S)

NH

(S)

HN

Tf+

2h-(2S)1c

TEA

Tf2O(S) OH

NH2

Triethylamine (2.4 mL) was added to a solution of L-valinole (0.837 g, 8.12 mmol) in CH2Cl2 (30

mL). Then trifluoromethanesulfonic anhydride (5.031 g, 17.8 mmol) was added dropwise to the

solution cooled to -78°C. The resulting yellow solution was heated to -30 °C and stirred overnight.

The solution was washed with HCl 0.1 M (120 mL) and brine (120 mL); organic phase was

anhydrified with Na2SO4, filtered and diluted with CH2Cl2 (30 mL). The solution was cooled to -40

°C and a solution of 1-naphthylmethylamine (0.441 g, 2.80 mmol) in CH2Cl2 (10 mL) was added

dropwise. After 30’, the solution was carried to room temperature. A white suspension immediately

formed. After 48 h, reaction was dried and purified by silica gel chromatography using n-

hexane:ethyl acetate = 7:3 as eluant. Main product was monoamine 2h-(2S) (560 mg, 1.50 mmol,

yield: 53%), while amine 3h-(2S,2’S) was obtained mixed with unreacted aziridine 1c and was

recrystallized from n-hexane in CH2Cl2 (182 mg, 0.310 mmol, yield: 11%). Crystals suitable for X-

Ray analysis of monoamine 2h-(2S) were obtained from CH2Cl2. Crystals suitable for X-Ray

analysis of amine 3h-(2S,2’S) were obtained by layering n-hexane (4 mL) to a CH2Cl2 solution (5

mL).

Synthesis of 2h-(2S) and 3h-(2S,2’S)

NTf

(S)

NH2+CH2Cl2

N

(S)

HN

Tf

(S)

HN

Tf

3h-(2S,2'S)

NH

(S)

HN

Tf+

2h-(2S)1c

9


A solution of 1-naphthylmethylamine (0.306 g, 1.94 mmol) in distilled CH2Cl2 (10 mL) was

added dropwise to a solution of (S)-2-isopropyl-1-triflylaziridine 1c (0.879 g, 4.01 mmol) in

distilled CH2Cl2 (20 mL) cooled to.-40°C. After 30 minutes the solution was carried to room

temperature. A white suspension immediately formed. The reaction was followed by TLC. After 48

h the white suspension was filtered giving pure monoamine 2h-(2S) (0.226 g, 0.604 mmol, yield:

31%); pure amine 3h-(2S,2’S) (0.600 g, 1.01 mmol, yield: 52%) were obtained by layering n-

hexane (5 mL) to a CH2Cl2 solution (5 mL).

SO2

F

F

a

b

c

d

e

f

g

h

i

l 12

34 5

6 7

NH

HN

2h-(2S)

F


i), 7.88 (1H, d, J = 8.0 Hz,

Hf), 7.80 (1H, pst, J = 8.0 Hz, ArH), 7.61-7.48 (2H, m, H

h-g), 7.43-7.42 (2H, m, ArH), 4.28 (1H, d,

J = 13.2 Hz, H6’

), 4.25 (1H, d, J = 13.2 Hz, H6), 3.35 (1H, ddd, J = 8.0 Hz, J = 4.2 Hz, J = 4.8 Hz,

H2), 3.02 (1H, dd, J = 12.9 Hz, J = 4.2 Hz, H

1’), 2.80 (1H, dd, J = 12.9 Hz, J = 4.8 Hz, H

1), 1.86

(1H, dq, J = 8.0 Hz, J = 6.8 Hz, H3), 0.97 (3H, d, J = 6,8 Hz, CH3

4), 0.92 (3H, d, J = 6,8 Hz, CH3

5),

0.51 (1H, bs, NH). 13

C NMR (75 MHz; CDCl3; T = 300 k) δ 129.0 (CH), 128.5 (C4H), 126.5 (CH),

126.0 (CH), 125.4 (CiH), 123.6 (C

gH), 61.0 (C

2H), 52.1 (C

6H2), 49.5 (C

1H2), 30.4 (C

3H), 19.2

(C4H3), 18.8 (C

5H3). Signals relative to quaternary carbons were not detected.

19F NMR (282 MHz;

CDCl3; T = 300 k) δ -77.7 (m). Elemental Analysis: Found: C, 54.7; H, 5.8; N, 7.3% Calc. for

C17H21F3N2O2S: C, 54.5; H, 5.6; N, 7.5%.

NHN

SO2

HN

Tf

3h-(2S,2'S)

F

Fa

b

c

d

e

f

g

h

i

l

1 2

34

6

7 F


i), 7.86 (1H, d, J = 8.1 Hz,

ArH), 7.81 (1H, d, J = 8.1 Hz, ArH), 7.58-7.42 (4H, m, ArH), 5.04 (2H, br, NH), 4.21 (1H, d, J =

10


13.2 Hz, H6), 4.05 (1H, d, J = 13.2 Hz, H

6’), 3.61 (2H, m, H

2), 2.72-2.58 (4H, m, H

1), 1.92 (2H, m,

H3), 0.81 (6H, d, J = 6.9 Hz, CH3

4), 0.65 (6H, d, J = 6.9 Hz, CH3

5).

13C NMR (75 MHz; CDCl3; T =

300 k) δ 134.1 (C), 133.1 (C), 132.2 (C), 128.9 (CH), 128.8 (CH), 128.6 (CH), 126.5 (CH), 126.1

(CH), 125.4 (CH), 123.9 (CiH), 119.5 (C7, q, J = 321 Hz), 58.7 (C

2H), 57.0 (C

6H2), 56.2 (C

1H2),

29.4 (C3H), 18.4 (C

4H3), 16.6 (C

5H3).

19F NMR (282 MHz; CDCl3; T = 300 k) δ -77.6 (bs).

Elemental Analysis: Found: C, 46.6; H, 5.4; N, 7.1% Calc. for C23H31F6N3O4S2: C, 46.7; H, 5.3; N,

7.1%.

Synthesis of 2i-(1R,2S) and 3i-(1R,2S,2’S)

NTf

(S)

NH2(R)

+CH2Cl2

N(R)

(S)

HN

Tf

(S)

HN

Tf

3i-(1R,2S,2'S)

NH

(R)(S)

HN

Tf+

2i-(1R,2S)1c

A solution of (R)-1-(1-naphthyl)ethyl amine (0.374 g, 2.18 mmol) in distilled CH2Cl2 (10 mL)

was added dropwise to a solution of (S)-2-isopropyl-1-triflylaziridine 1c (0.968 g, 4.46 mmol) in

distilled CH2Cl2 (30 mL) cooled to.- 40 °C. After 30 minutes the solution was carried to room

temperature. A white suspension immediately formed. The reaction was followed by TLC. After 90

h, the mixture was dried and purified by silica gel chromatography using n-hexane:ethyl acetate =

7:3 as eluant, obtaining a monoamine 2i-(1R,2S) (0.0932 g, 0.240 mmol, yield: 11%) and pure

amine 3i-(1R,2S,2’S) (1.180 g, 1.95 mmol, yield: 89%).

SO2

F

F

a

b

c

d

e

f

g

h

i

l 12

34 5

6

7

NH

HN

2i-(1R,2S)

F8


i), 7.90 (1H, d, J = 7.7 Hz,

ArH), 7.79 (1H, d, J = 8.0 Hz, ArH), 7.59-7.47 (4H, m, ArH), 4.67 (1H, q, J = 6.5 Hz, H6), 3.33

(1H, m, H2), 3.20 (2H, br, NH), 2.84 (1H, dd, J = 13.0 Hz, J = 5.0 Hz, H

1), 2.70 (1H, dd, J = 13.0

Hz, J = 4.3 Hz, H1’

), 1.87 (1H, m, H3), 1.57 (3H, d, J = 6.6 Hz, CH3

7), 0.93 (3H, d, J = 6.8 Hz,

11


CH34), 0.84 (3H, d, J = 6.8 Hz, CH3

5).

13C NMR (75 MHz; CDCl3; T = 300 k) δ 139.7 (C), 134.2

(C), 131.2 (C), 129.3 (CH), 128.1(CH), 126.4 (CH), 125.9 (CH), 125.8 (CH), 122.9 (CH), 122.6

(CiH), 119.9 (C

8, q, J = 321 Hz), 60.9 (C

2H), 53.8 (C

6H), 47.8 (C

3H2), 30.5 (C

3H), 23.1 (C

7H3),

19.2 (C4H3), 18.8 (C

5H3).

19F NMR (282 MHz; CDCl3; T = 300 k) δ -77.4 (s). Elemental Analysis:

Found: C, 55.7; H, 6.2; N, 7.0% Calc. for C18H23F3N2O2S: C, 55.7; H, 6.0; N, 7.2%. MS (EI): m/z

388 (M+), 373 (M

+-CH3), 255 (M

+-Tf), 184 (M

+-204).

NHN

SO2

HN

Tf

3i-(1R,2S,2'S)

F

Fa

b

c

d

e

f

g

h

i

l

1 2

34

6

7

5

F8


i), 7.85 (1H, d, J = 9.4 Hz,

ArH), 7.80 (1H, d, J = 7.8 Hz, ArH), 7.54-7.48 (3H, m, ArH), 7.46 (1H, pst, J = 7.4 Hz, ArH), 4.88

(1H, q, J = 6.5 Hz, H6), 4.68 (2H, br, NH), 3.56 (2H, m, H

2), 2.75 (2H, dd, J = 13.5 Hz, J = 4.9 Hz,

H1), 2.63 (2H, dd, J = 13.5 Hz, J = 9.7 Hz, H

1’), 1.70 (2H, m, H

3), 1.57 (3H, d, J = 6.7 Hz, CH3

7)

0.88 (6H, d, J = 6.9 Hz, CH34), 0.31 (6H, d, J = 6.8 Hz, CH3

5).

13C NMR (75 MHz; CDCl3; T = 300

k) δ 137.4 (C), 134.3 (C), 132.1 (C), 129.1 (CH), 128.7(CH), 125.9 (CH), 125.8 (CH), 125.3 (CH),

125.1 (CH), 123.5 (CiH), 119.6 (C

8, q, J = 321 Hz), 59.2 (C

2H), 53.9 (C

6H), 53.2(C

1H2), 27.7

(C3H), 19.5 (C

4H3), 14.6 (C

5H3), 12.4 (C

7H3).

19F NMR (282 MHz; CDCl3; T = 300 k) δ - 77.56 (s).

Elemental Analysis: Found: C, 47.4; H, 5.8; N, 6.6% Calc. for C24H33F6N3O4S2: C, 47.6; H, 5.5; N,

6.9%. MS (EI): m/z 590 (M+-CH3), 401 (M

+-Tf).

Synthesis of 4b

N

NN

N

Ts

4b

TsN

HN

Ts

HN

Ts

+N

ClCl

K2CO3

CH3CN

3b

12


A solution of amine 3b (0.842 g, 1.53 mmol), 2,6-bis(chloromethyl) pyridine (0.269 g, 1.53

mmol) and micronized anhydrous potassium carbonate (0.633 g, 4.58 mmol) in distilled acetonitrile

(35 mL) was stirred and heated under reflux for 45 hours. The resulting mixture was washed with

water end extracted with ethyl acetate, dried and purified by silica gel chromatography using

toluene:dichloromethane:isopropanol = 90:10:5 as eluant, obtaining a white solid 4b (0.508 g, 0.776

mmol, yield: 51%).

N

NN

N

SO2

Ts

4b

1

2

3

4

5

14

13

6

7

8

9

10

11

12

ab

c

d

e

l

i

h

g

f

m

no

p

r

q


i), 7.90-7.83 (2H, m, ArH),

7.76 (1H, pst, J = 7.8 Hz, Hr), 7.50 (4H, d, J = 8.2 Hz, H

n), overlapping with 7.52-7.23 (6H, m,

ArH), 7.19 (4 H, d, J = 8.2 Hz, Ho), 4.31 (4H, br, CH2

2), 3.93 (2H, br, CH2

13), 3.07 (4H, m, CH2

4),

2.39 (6H, s, CH314

) overlapping with 2.36 (4H, m, CH25). Elemental Analysis: Found: C, 66.2; H,

5.8; N, 8.4% Calc. for C36H38N4O4S2: C, 66.0; H, 5.8; N, 8.6%.

Synthesis of 4e-(4S,8S)

N

NN

(S)N

(S)Ts

4e-(4S,8S)

TsN

(S)

HN

Ts

(S)

HN

Ts

+N

ClCl

K2CO3

CH3CN

3e-(2S,2S')

A solution of amine 3e-(2S,2S’) (0.330 g, 0.520 mmol), 2,6-bis(chloromethyl) pyridine (0.0914 g,

0.520 mmol) and micronized anhydrous potassium carbonate (0.228 g, 1.65 mmol) in distilled

acetonitrile (12 mL) was stirred and heated under reflux for 45 hours. The resulting mixture was

washed with water end extracted with ethyl acetate, dried and purified by silica gel chromatography

13


using toluene:dichloromethane:isopropanol = 90:10:5 as eluant, obtaining a white solid 4e-(4S,8S)

(0.215 g, 0.291 mmol, yield: 56%).

N

NN

N

SO2

Ts

4e-(4S,8S)

1

2

3

4

5 14

15

1613

6

7

8

9

10

11

12

ab

c

d

e

l

i

h

g

f

m

no

p 17

r

q


i), 7.86 (1H, d, J = 8.0 Hz,

ArH), 7.76 (1H, d, J = 8.0 Hz, ArH) 7.66-7.58 (3H, m, ArH), 7.53 (1H, pt, J = 7.6 Hz, ArH), 7.43

(1H, pt, J = 7.6 Hz, ArH), 7.29-7.11 (6H, m, ArH), 7.02 (4H, d, J = 7.8 Hz, Ho), 4.72 (2H, d, J =

15.6 Hz, H2), 4.30 (1H, d, J = 13.5 Hz, H

13), 4.18 (1H, d, J = 13.5 Hz, H

13’), 3.78 (2H, d, J = 15.6

Hz, H2’

), 3.68 (2H, dd, J = 15.6 Hz J = 6.9 Hz, H5), 3.51 (2H, m, H

4), 2.29 (6H, s, CH3

17), 2.19 (2H,

m, H5’

), 1.19 (2H, m, H), 0.58 (6H, d, J = 6.9 Hz, CH315

), 0.48 (6H, br, CH316

). 13

C NMR (75 MHz;

CDCl3; T = 300 k) δ 156.5 (C), 142.3 (C), 139.3 (C), 137.2 (CH), 135.7 (C), 134.0 (C), 132.7 (C),

128.9 (CH), 128.5 (CH), 128.0 (CH), 127.8 (CH), 127.7 (CH), 125.9 (CH), 125.7 (CH), 125.4

(CH), 125.0 (CH), 120.2 (CH), 65.6 (C4H), 57.2 (C

13H2), 53.1 (C

5H2), 48.9 (C

2H2), 30.5 (C

14H),

21.4 (C17

H3), 20.4 (C15

H3), 20.2 (C16

H3). Elemental Analysis: Found: C, 68.4; H, 6.8; N, 7.4%

Calc. for C42H50N4O4S2: C, 68.3; H, 6.8; N, 7.6%. MS (FAB): m/z 739 (M++1). []D

20 = + 1.04 (c

1.01 in CHCl3).

Synthesis of 4f-(13R,4S,8S)

N

NN

(S)N

(S)Ts

(R)

4f-(13R,4S,8S)

TsN(R)

(S)

HN

Ts

(S)

HN

Ts

+N

ClCl

K2CO3

CH3CN

3f-(1R,2S,2'S)

14


A solution of amine 3f-(1R,2S,2’S) (0.715 g, 1.10 mmol), 2,6-bis(chloromethyl) pyridine (0.194

g, 1.10 mmol) and micronized anhydrous potassium carbonate (0.608 g, 4.40 mmol) in distilled

acetonitrile (37 mL) was stirred and heated under reflux for 116 h. The resulting mixture was


using n-hexane:ethyl acetate = 6:4 as eluant, obtaining a white solid 4f-(13R,4S,8S) (0.471 g, 0.626

mmol, yield: 57%).

N

NN

N

SO2

Ts

4f-(13R,4S,8S)

1

2

3

4

5

14

15

16

13

6

7

8

9

10

11

12

ab

c

d

e

l

i

h

g

f

m

no

p

17

r

q

18


i), 7.89 (1H, m, ArH), 7.83

(1H, d, J = 8.1 Hz, ArH), 7.69 (1H, d, J = 8.1 Hz, ArH), 7.64-7.42 (8H, m, ArH), 7.12 (4H, d, J =

7.8 Hz, Ho), 7.05 (2H, m, ArH), 5.18 (1H, m, H

13), 4.72 (2H, m, H

2), 3.94-3.82 (6H, m, H), 2.63-

2.60 (2H, m, H), 2.40 (2H, m, H) overlapping with 2.33 (6H, s, CH318

), 1.57 (3H, d, J = 6.5 Hz,

CH314

), 0.44 (12H, m, CH316-17

). 13

C NMR (75 MHz; CDCl3; T = 300 k) δ 156.5 (C), 142.5 (C),

142.2 (C), 138.9 (C), 137.0 (CH), 134.2 (C), 131.7 (C), 129.2 (CoH), 128.9 (CH), 127.8 (C

nH),

127.0 (CH), 126.0 (CH), 125.9 (CH), 125.8 (CH), 125.2 (CH), 124.0 (CiH), 120.7 (CH), 66.5 (CH),

50.8 (CH2), 49.5 (CH2), 30.0 (CH), 23.8 (C14

H3), 21.5 (C18

H3), 21.1 (C16

H3). A signal relative to a

CH was not detected. 15

N NMR (40 MHz; CDCl3; T = 300 k) δ 33.2 (N6). The signals relative to N-

Ts and N12

were not detected. 1H NMR (300 MHz; C6D5CD3; T = 300 k) δ 8.74 (1H, d, J = 8.8 Hz,

Hi), 7.99 (1H, d, J = 7.2 Hz, H

b), 7.68 (4H, pst, J = 8.0 Hz, H

n) overlapping with 7.69-7.66 (1H, m,

Hg), 7.57-7.47 (2H, m, H

d and H

h), 7.38 (1H, pst, J = 7.5 Hz, H

c), 7.29 (1H, pst, J = 7.5 Hz, H

f),

7.05-7.03 (1H, m, Hr), 6.86 (4H, d, J = 8.0 Hz, H

o), 6.68 (2H, d, J = 7.8 Hz, H

q), 5.39 (1H, q, J =

6.6 Hz, H13

), 4.62 (2H, d, J = 15.9 Hz, H2), 4.14-4.06 (4H, m, H

4 and H

5), 4.02-3.93 (2H, m, H

2’),

15


2.96 (2H, d, J = 15.0 Hz, H5’

), 2.02 (6H, s, CH318

), 1.68 (3H, d, J = 6.6 Hz, CH314

), 1.39 (2H, m,

H15

), 0.58 (12H, m, CH316-17

). 13

C NMR (75 MHz; C6D5CD3; T = 300 k) δ 157.4 (C), 142.7 (C),

141.9 (C), 140.4 (C), 136.3 (CrH), 134.9 (C), 132.5 (C), 129.0 (C

oH), 128.2 (C

nH), 127.2 (C

dH),

126.3 (CbH), 125.9 (C

dH) overlapping with 125.9 (C

hH), 125.2 (C

fH), 124.5 (C

iH), 120.5 (C

qH),

66.4 (C4H), 57.2 (C

13H), 51.4 (C

2-5H2), 30.9 (C

15H), 23.5 (C

14H3), 21.0 (C

16H3), 20.8 (C

18H3). A

signal relative to an aromatic carbon was not detected. Elemental Analysis: Found: C, 68.4; H, 7.4;

N, 7.1% Calc. for C43H52N4O4S2: C, 68.6; H, 7.0; N, 7.4%. MS (FAB): m/z 753 (M++1).

Synthesis of 4g-(13S,4S,8S)

N

NN

(S)N

(S)Ts

(S)

4g-(13S,4S,8S)

TsN(S)

(S)

HN

Ts

(S)

HN

Ts

+N

ClCl

K2CO3

CH3CN

3g-(1S,2S,2'S)

A solution of amine 3g-(1S,2S,2’S) (0.0888 g, 0.137 mmol), 2,6-bis(chloromethyl) pyridine

(0.0240 g, 0.136 mmol) and micronized anhydrous potassium carbonate (0.0700 g, 3.70 mmol) in

distilled acetonitrile (6 mL) was stirred and heated under reflux for 53 h. The resulting mixture was


using n-hexane:dichloromethane:isopropanol = 80:17.5:2.5 as eluant, obtaining a white solid 4g-

(13S,4S,8S) (0.0512 g, 0.0679 mmol, yield: 50%).

N

NN

N

SO2

Ts

4g-(13S,4S,8S)

1

2

3

4

5

14

15

16

13

6

7

8

9

10

11

12

ab

c

d

e

l

i

h

g

f

m

no

p

17

rq

18

1H NMR (300 MHz; CDCl3;T = 300 k) δ 8.54 (1H, m, Hi), 7.89 (1H, m, ArH), 7.85 (1H, d, J =

8.1 Hz, ArH), 7.77 (1H, d, J = 8.1 Hz, ArH), 7.64-7.41 (8H, m, ArH), 7.09-6.99 (6H, m, ArH), 5.01

16


(1H, m, H13), 4.76 (2H, m, H2), 3.86 (2H, m, H2’), 3.77 (2H, m, H4), 3.55 (2H, m, H5), 2.36 (2H, m,

H5‘), 2.29 (6H, s, CH318), 1.48 (3H, d, J = 6.6 Hz, CH3

14), 1.34-1.23 (2H, m, H15), 0.60 (6H, m,

CH316), 0.38 (6H, m, CH3

17). 13C NMR (75 MHz; CDCl3; T = 300 k) δ 156.3 (C), 142.3 (C), 141.4

(C), 139.2 (C), 137.3 (CH), 134.1 (C), 132.5 (C), 128.9 (CnH), 128.8 (CH), 127.7 (CoH), 127.6

(CH), 126.7 (CH), 126.2 (CH), 125.4 (CH), 124.1 (CH), 120.7 (CH), 66.0 (C4H), 56.0 (C13H), 51.0

(C5H2), 49.3 (C2H2), 30.2 (C15H), 21.4 (C18H3), 20.8 (C14H3), 20.1 (C16H3) overlapping with 20.1

(C17H3). Elemental Analysis: Found: C, 68.6; H, 7.2; N, 7.4% Calc. for C43H52N4O4S2: C, 68.6; H,

7.0; N, 7.4%. MS (FAB): m/z 753 (M++1).

Synthesis of 4h-(4S,8S)

N

NN

(S)N

(S)Tf

4h-(4S,8S)

TfN

(S)

HN

Tf

(S)

HN

Tf

+N

ClCl

K2CO3

CH3CN

3h-(2S,2'S)

A solution of amine 3h-(2S,2’S) (0.350 g, 0.592 mmol), 2,6-bis(chloromethyl) pyridine (0.108 g,

0.612 mmol) and micronized anhydrous potassium carbonate (0.245 g, 1.75 mmol) in distilled

acetonitrile (15 mL) was stirred and heated under reflux for 28 h. The mixture was dried and

purified by silica gel chromatography using toluene:dichloromethane:isopropanol = 85:10:5 as

eluant, obtaining a yellow oil 4h-(4S,8S) (0.218 g, 0.314 mmol, yield: 53%).

N

NN

N

SO2

Tf F

F

4h-(4S,8S)

1

2

3

4

5 14

15

1613

6

7

8

9

10

11

12

ab

c

d

e

l

i

h

g

f

17

r

q

F

1H NMR (400 MHz; C6D6; T = 300 k) δ 7.78-7.76 (2H, m, ArH), 7.72-7.66 (2H, m, ArH), 7.45-

7.37 (2H, m, ArH), 7.27-7.22 (1H, m, ArH),7.17-7.07 (3H, m, ArH), 4.77-4.47 (4H, m, CH), 3.89-

17


3.85 (4H, m, H), 3.10-3.05 (2H, m, H), 1.09 (2H, m, H14

), 0.69 (6H, bs, CH315

), 0.40 (6H, bs,

CH316

). Two CH signals were not detected. At room temperature, this compound gives very broad

signals in CDCl3. 13

C NMR (100 MHz; C6D6; T = 300 k) δ 136.9 (CH), 129.1 (CH), 128.4 (CH),

128.3 (CH), 126.2 (CH), 126.0 (CH), 125.4 (CH), 56.9 (C2H), 53.2 (C

13H2), 49.9 (CH2), 29.4

(C14

H), 19.9 (C15

H3), 19.6 (C16

H3). Signals relative to quaternary carbons and aromatic CH were

not detected. 19

F NMR (376 MHz; C6D6; T = 300 k) δ - 74.5 (bs). Elemental Analysis: Found: C,

51.8; H, 5.4; N, 8.0% Calc. for C30H36F6N4O4S2: C, 51.9; H, 5.2; N, 8.1%. MS (FAB): m/z 695

(M++1), 561 (M+-Tf). []D20

= - 0.85 (c 0.860 in CHCl3).

Synthesis of 4i-(13R,4S,8S) under conventional heating

N

NN

(S)N

(S)

Tf

(R)

4i-(13R,4S,8S)

TfN(R)

(S)

HN

Tf

(S)

HN

Tf

+N

ClCl

K2CO3

CH3CN

3i-(1R,2S,2'S)

A solution of amine 3i-(1R,2S,2’S) (0.402 g, 0.665 mmol), 2,6-bis(chloromethyl) pyridine (0.118

g, 0.671 mmol) and micronized anhydrous potassium carbonate (0.290 g, 2.10 mmol) in distilled

acetonitrile (20 mL) was stirred and heated under reflux for 110 hours. The resulting mixture was


using toluene:dichloromethane:isopropanol = 85:10:5 as eluant, obtaining a white solid 4i-

(13R,4S,8S) (0.192 g, 0.271 mmol, yield: 39%).

Synthesis of 4i-(13R,4S,8S) under microwave heating

N

NN

(S)N

(S)

Tf

(R)

4i-(13R,4S,8S)

TfN(R)

(S)

HN

Tf

(S)

HN

Tf

+N

ClCl

K2CO3

CH3CN

3i-(1R,2S,2'S)

18


This synthesis can be performed in the air. A solution of amine 3i-(13R,4S,8S) (0.387 g, 0.639

mmol), 2,6-bis(chloromethyl) pyridine (0.116 g, 0.658 mmol) and micronized potassium carbonate

(0.265 g, 1.92 mmol) in distilled acetonitrile (13 mL) was added in a microwave tube. The mixture

was stirred and heated by microwave irradiation for 4 hours and 30 minutes at 150°C. The resulting

mixture was washed with water end extracted with ethyl acetate, dried and purified by silica gel

chromatography using toluene:dichloromethane:isopropanol = 85:10:5 as eluant, obtaining a white

solid 4i-(13R,4S,8S) (0.250 g, 37.8 mmol, yield: 59%).

N

NN

N

SO2

Tf F

F

4i-(13R,4S,8S)

1

2

3

4

5

14

15

16

13

6

7

8

9

10

11

12

ab

c

d

e

l

i

h

g

f

17

rq

18 F


i), 7.81-7.78 (2H, m, ArH), 7.68-7.62

(2H, m, ArH), 7.52-7.40 (3H, m, ArH), 7.20-7.17 (2H, m, ArH), 5.16 (1H, q, J = 6.3 Hz, H13

), 4.91

(2H, d, J = 16.0 Hz, H2), 4.40 (2H, d, J = 16.0 Hz, H

2’), 3.82 (2H, m, H

5), 2.98 (2H, m, H

5’), 1.65

(2H, m, H4), 1.51 (3H, d, J = 6.3 Hz, CH3

14), 0.73 (6H, bs, CH3

16), 0.44 (6H, bs, CH3

17). Two CH

signals were not detected. 13

C NMR (75 MHz; CDCl3; T = 300 k) δ 155.1 (C), 141.2 (C), 137.9

(CH), 134.2 (C), 131.6 (C), 128.9 (CH), 127.2 (CH), 126.4 (CH), 126.0 (CH), 125.3 (CH), 123.6

(CH), 122.1 (CH), 69.1 (C4H), 57.4 (C

13H), 50.9 (C

2H2), 50.4 (C

5H2),29.9 (C

15H), 24.0 (C

14H3),

21.0 (C16

H3), 19.3 (C17

H3). 15

N NMR (40 MHz; CDCl3; T = 300 k) δ 31.35 (N6), The signal relative

to N-Tf and N12

were not detected. 19

F NMR (282 MHz; CDCl3; T = 300 k) δ - 74.15 (s). Elemental

Analysis: Found: C, 52.4; H, 5.3; N, 8.0% Calc. for C31H38F6N4O4S2: C, 52.5; H, 5.4; N, 7.9%. MS

(FAB): m/z 709 (M++1), 575 (M+-133). []D20

= + 117 (c 0.005 in CH2Cl2).

19


Synthesis of 5c-(13S)

Ligand 4c-(13S) (0.200 g, 0.323 mmol) was dissolved in distilled dichloroethane (5 mL). Triflic

acid (0.0530 g, 0.355 mmol) was added and the solution stirred for 2 hours. The solution was dried,

then n-hexane (10 mL) was added and the solid filtered in air (0.055 g, 0.0710 mmol, yield: 22%).

1H NMR (300 MHz; CDCl3; T = 300 k) δ 11.38 (1H, s, NH), 7.80 (2H, d, J = 8.2 Hz, ArH), 7.71

(1H, pt, J = 7.7 Hz, ArH), 7.61 (2H, d, J = 8.2 Hz, ArH), 7.52 (2H, m, ArH), 7.45-7.39 (5H, m,

ArH), 7.34 (2H, d, J = 8.1 Hz, ArH), 7.22 (1H, d, J = 7.7 Hz, ArH), 7.04 (1H, d J = 7.7 Hz, ArH),

5.60 (1H, q, J = 7.0 Hz, H13

), 4.65 (1H, d, J = 17.1 Hz, CH2), 4.17 (1H, d, J = 17.1 Hz, CH2), 4.16-

4.09 (2H, m, CH2), 3.88 (1H, m, CH2), 3.74-3.64 (3H, m, CH2), 3.50-3.39 (3H, m, CH2), 2.50 (3H,

s, CH3), 2.45 (3H, s, CH3) overlapping with 2.45-2.40 (1H, m, CH2), 1.85 (3H, d, J = 7.0 Hz,

CH314

) overlapping with 1.85-1.80 (1H, m, CH2). 13C NMR (75 MHz; CDCl3; T = 300 k) δ 156.8

(C), 155.5 (C), 145.4 (C), 144.8 (C), 139.6 (CH), 134.4 (C), 133.4 (C), 132.7 (C), 130.7 (CH),

130.6 (CH), 130.4 (CH), 129.9 (CH), 129.5 (CH), 127.9 (CH), 127.6 (CH), 122.8 (CH), 122.2

(CH), 58.3 (C13

H), 52.8 (CH2), 51.7 (CH2), 51.5 (CH2), 46.2 (CH2), 44.4 (CH2), 21.8 (CH3Ts), 21.7

(CH3Ts). One CH2 and C14

H3 signals were not detected. 15

N NMR (40 MHz; CDCl3; T = 300 k) δ

282,0 (N12), 52.2 (N6). The signals relative to N-Ts were not detected. Elemental Analysis: Found:

20


C, 52.9; H, 5.1; N, 7.6% Calc. for C34H39F3N4O7S3: C, 53.1; H, 5.1; N, 7.3%. m/z 619.2 (M+ -

CF3SO3-).

5c-(13R) was synthesized in the same way starting from 4c-(13R).

Synthesis of 5d-(13S)

Ligand 4d-(13S) (0.200 g, 0.299 mmol) was dissolved in distilled dichloroethane (5 mL). Triflic

acid (0.046 g, 0.329 mmol) was added and the solution stirred for 2 hours. The solution was dried,

then n-hexane (10 mL) was added and the solid filtered in air (0.118 g, 0.144 mmol, yield: 48%).

1H NMR (400 MHz; CDCl3; T = 300 k) δ 10.68 (1H, s, NH), 8.20 (1H, d, J = 8.6 Hz, ArH), 7.94

(1H, d, J = 8.2 Hz, ArH), 7.87-7.81 (4H, m, ArH), 7.72 (1H, pt, J = 7.7 Hz, ArH), 7.58 (1H, pt,

J = 7.7 Hz, ArH), 7.45 (2H, d, J = 8.1 Hz, ArH), 7.41 (2H, d, J = 8.1 Hz, ArH), 7.36-7.30 (2H, m,

ArH), 7.21 (2H, d, J = 8.1 Hz, ArH), 6.81-6.77 (2H, m, ArH), 6.22 (1H, q, J = 6.6 Hz, H13

), 4.53

(1H, m, CH2) overlapping with 4.48 (1H, d, J = 16.6 Hz, CH2), 4.07 (1H, d, J = 16.6 Hz, CH2),

4.00-3.86 (3H, m, CH2), 3.70 (1H, d, J = 16.3 Hz, CH2), 3.52-3.30 (3H, m, CH2), 2.49 (3H, s, CH3),

2.35 (3H, s, CH3), 2.20 (1H, m, CH2), 2.06 (3H, d, J = 6.6 Hz, CH314

), 1.73 (1H, m, CH2). 13C NMR

21


(100 MHz; CDCl3; T = 300 k) δ 157.4 (C), 156.9 (C), 145.5 (C), 144.7 (C), 140.0 (CH), 133.9 (C),

133.8 (C), 132.5 (C), 131.5 (CH), 130.7 (CH), 130.7 (C), 130.1 (CH), 129.4 (CH), 129.3 (C), 128.0

(CH), 127.9 (CH), 127.5 (CH), 126.9 (CH), 126.8 (CH), 126.1 (CH), 122.8 (CH), 122.7 (CH),

121.9 (CH), 55.2 (C13

H), 54.3 (CH2), 53.8 (CH2), 53.5 (CH2), 52.9 (CH2), 47.8 (CH2), 47.2 (CH2),

21.8 (CH3Ts), 21.6 (CH3Ts), 11.3 (C14

H3). 15N NMR (40 MHz; CDCl3; T = 300 k) δ 282,1 (N12),

52.0 (N6). The signals relative to N-Ts were not detected. Elemental Analysis: Found: C, 55.4; H,

5.2; N, 6.4% Calc. for C38H41F3N4O7S3: C, 55.7; H, 5.0; N, 6.8%. MS (FAB): m/z 669.2 (M+-

CF3SO3-). []D

20 = - 168 (c 0.5 in CH2Cl2).

5d-(13R) was synthesized in the same way starting from 4d-(13R). []D20

= + 168 (c 0.5 in

CH2Cl2)

Synthesis of 6b

Copper (I) triflate benzene complex (0.0298 g, 0.0591 mmol) was added to a solution of

macrocycle 4b (0.0891 g, 0.118 mmol) in dichloroethane (10 mL). The solution was stirred at room

temperature for one hour, concentrated to 5 mL and then 10 mL of n-hexane were layered. Then the

solid was filtered and dried in vacuo under nitrogen, obtaining complex 6b as a solid (0.111 g,

0.115 mmol, yield: 97%).

22



i), 8.08-8.05 (2H, m, ArH),

7.92 (1H, m, ArH), 7.85-7.75 (2H, m, Hr) 7.65-7.52 (7H, m, ArH), 7.42-7.37 (4H, m, ArH), 7.27-

7.17 (2H, m, ArH), 4.89 (2H, d, J = 14.7 Hz, H2 and H

10), 4.46 (2H, m, CH2

13), 3.68 (2H, d, J =

14.7 Hz, H2 and H

10), 3.53 (2H, m, H

4 and H

8), 2.93 (2H, m, H

4 and H

8), 2.82 (2H, m, H

5 and H

7),

2.50 (6H, s, CH314

), overlapping with 2.58-2.50 (2H, m, H5 and H

7). Elemental Analysis: Found: C,

51.4; H, 4.3; N, 6.1% Calc. for C37H38CuF3N4O7S3: C, 51.2; H, 4.4; N, 6.6%.

Synthesis of 6f

Copper (I) triflate benzene complex (0.0298 g, 0.0591 mmol) was added to a solution of

macrocycle 4f-(13R,4S,8S) (0.0891 g, 0.118 mmol) in dichloroethane (10 mL). The solution was

stirred at room temperature for one hour, concentrated to 5 mL and then 10 mL of n-hexane were

layered. Then the solid was filtered and dried in vacuo under nitrogen, obtaining complex 6f as a

solid (0.111 g, 0.115 mmol, yield: 97%).

23



i), 7.93 (1H, d, J = 8.0 Hz,

ArH), 7.87 (4H, d, J = 8.1 Hz, Hn

and Hn’

), 7.80-7.69 (3H, m, ArH), 7.62-7.40 (7H, m, ArH), 7.23-

7.16 (2H, m, ArH), 5.95 (1H, q, J = 6.6 Hz, H14

), 5.25 (1H, d, J = 20 Hz, H2), 4.79 (1H, d, J = 12.7

Hz, H7), 4.71 (1H, d, J = 14.6 Hz, H

10), 4.62 (1H, d, J = 20 Hz, H

2’), overlapping with 4.61 (1H, m,

H8), 4.01 (1H, d, J = 14.6 Hz, H

10’), 2.78 (1H, d, J = 12.7 Hz, H

7’), 2.57 (3H, s, CH3

18 or 18’),

overlapping with 2.57 (1H, m, H4), 2.52 (3H, s, CH3

18’ or 18), 2.42-2.37 (1H, m, H

5), 2.30-2.15 (2H,

m, H5’

and H15’

), 2.10 (3H, d, J = 6.8 Hz, CH314

), 1.59 (1H, m, H15

), 0.90 (3H, d, J = 6.7 Hz,

CH316’

), 0.68 (3H, d, J = 6.2 Hz, CH317

), 0.29 (3H, d, J = 6.5 Hz, CH317’

), -0.49 (3H, d, J = 6.2 Hz,

CH316

). 13

C NMR (75 MHz; CDCl3; T = 300 k) δ 155.7 (C1 or 11

), 151.2 (C11 or 1

), 145.6 (Cp’

), 145.3

(Cp), 140.4 (CH), 134.8 (C

a), 134.5 (C

l), 133.9 (C), 132.1 (C), 131.5 (CH), 130.4 (C

o), 129.8 (CH),

129.3 (CH), 128.9 (CH), 127.7 (CHh), 127.3 (CH), 126.4 (CH), 125.2 (CH), 124.8 (CH), 124.5

(CH), 123.9 (CH), 122.8 (Ci), 64.7 (C

4H), 62.0 (C

8H), 57.4 (C

5H2), 57.1 (C

10H2), 56.4 (C

13H), 55.5

(C7H2), 46.8 (C

2H2), 29.9 (C

15’H), 27.1 (C

15H), 24.5 (C

14H3), 22.4 (C

16’H3), 21.9 (C

18 and 18’H3), 21.3

(C17’

H3), 20.3 (C17

H3), 18.5 (C16

H3), 19

F NMR (282 MHz; CDCl3; T = 300 k) δ - 78.58 (s).

Elemental Analysis: Found: C, 54.7; H, 5.2; N, 5.7% Calc. for C44H52CuF3N4O7S3: C, 54.7; H, 5.4;

N, 5.8%.

24


Synthesis of 6i

Copper (I) triflate benzene complex (0.231 g, 0.171 mmol) was added to a solution of macrocycle

4f-(13R,4S,8S) (0.0860 g, 0.325 mmol) in dichloroethane (7 mL). The solution was stirred at room

temperature for one hour and then 50 mL of n-hexane were layered. Then the solid was filtered and

dried in vacuo under nitrogen, obtaining complex 6i as a solid (0.140 g, 0.152 mmol, yield: 45%).

1H NMR (300 MHz; CDCl3; Me4Si; T = 300 k) δ 8.16 (1H, d, J = 8.9 Hz, H

i), 8.01 (2H, pst, J =

7.5 Hz, ArH), 7.80 (1H, pst, J = 7.7 Hz, ArH), 7.73 (1H, m, ArH), 7.68-7.63 (3H, m, ArH), 7.31

(1H, m, ArH), 7.20 (1H, m, ArH), 6.46 (1H, m, H13

), 5.10-4.70 (5H, m, H), 4.40-4.01 (3H, m, H),

3.50 (1H, m, H), 2.95 (1H, m, H), 2.50-2.36 (1H, m, H), 2.06 (3H, d, J = 6.8 Hz, CH314

), 1.52 (1H,

m, H), 1.27 (3H, bs, CH3i-prop), 1.10 (3H, bs, CH3i-prop), 0.80 (3H, bs, CH3i-prop), 0.47 (3H, bs, CH3i-

prop). 13

C NMR (75 MHz; CDCl3; T = 300 k) δ 139.3 (CH), 131.7 (CH), 130.4 (CH), 128.5 (CH),

127.4 (CH), 125.7 (CH), 122.6 (CH), 121.3 (CiH), 57.1 (CH2), 43.6 (CH2), 31.7 (CH2), 28.8 (CH),

22.8 (CH2), 21.3 (C14

H3), 20.8 (CH3 i-prop), 14.3 (CH3 i-prop). Signals relative to quaternary carbons,

aromatic CH, aliphatic CH and CH3 were not detected. Elemental Analysis: Found: C, 41.8; H, 3.7;

N, 5.8% Calc. for C32H38CuF9N4O7S3: C, 41.7; H, 4.2; N, 6.1%.

25


Synthesis of 7d

N

NN

N

TsTs

CH3

Cu (OTf)

6d

N

NN

N

TsTs

CH3

Cu (OTf)

O13C

7d

13CO

C2H4Cl2

20 mg of copper(I) complex 6d were added to anhydrous and degassed CDCl3 in a NMR tube and

the solution was saturated with 13

CO, obtaining 7d.

N

NN

N

SO2

Cu

7d

(OTf)SO2

m

no

p1

2

3

45

14

15

13

6

78

9

10

11

12

ab

c

d

e

l

i

h

g

f

rq

15'

q'

m'

n'o'

p'

O13C


i), 7.96 (1H, d, J = 8.3 Hz,

ArH), 7.88 (2H, d, J = 8.5 Hz, Hn or n’

), 7.84-7.82 (1H, m, ArH) overlapping with 7.81 (2H, d, J =

8.2 Hz, Hn’ or n

), 7.73 (1H, m, Hh), 7.68-7.59 (2H, m, ArH), 7.53 (2H, d, J = 8.5 Hz, H

o or o’), 7.49

(1H, m, ArH), 7.40 (2H, d, J = 8.2 Hz, Ho’ or o

), 7.31 (1H, m, ArH), 7.23-7.16 (2H, m, ArH), 6.19

(1H, q, J = 6.8 Hz, H13

), 5.24 (1H, d, J = 17.7 Hz, H10 or 2

), overlapping with 5.19 (1H, d, J = 15.0

Hz, H2 or 10

), 4.80 (1H, m, H7), 4.30 (1H, m, H

7), 3.98 (1H, d, J = 17.7 Hz, H

10 or 2), 3.64 (1H, d, J =

15.0 Hz, H2 or 10

), 3.09-2.64 (4H, m, CH), 2.56 (3H, s, CH315 or 15’

), 2.47 (3H, s, CH315’ or 15

), 2.36-

2.28 (1H, m, H7 or 5

), 2.16 (3H, J = 6.8 Hz, CH314

) overlapping with 2.15-2.07 (1H, m, H8 or 4

).

Highlighted signals are relative to compound 5d. 13

C NMR (75 MHz; CDCl3; T = 300 k) δ 184.4

(free 13

CO), 171.1 (13

CO), 156.1 (C), 152.2 (C), 145.9 (C), 140.4 (CH), 135.2 (C), 134.6 (C), 132.2

(C), 130.7 (2 CHTs), 130.0 (CH), 129.2 (CHTs), 129.2 (CH), 128.0 (CHTs), 126.8 (ChH), 126.1 (CH),

125.5 (2 CH), 124.2 (CH), 123.6 (CH), 122.7 (CiH), 56.8 (C

2H2), 56.4 (C

2’H2), 55.3 (C

13H), 52.7

(C8H2), 51.9 (C

5H2), 50.7 (C

7H2), 47.5 (C

4H2), 23.4 (C

14H3), 21.9 (C

15H3), 21.7 (C

15’H3).

15N NMR

26


(40 MHz; CDCl3; T = 300 k) δ 243.5 (N12

), 39.8 (N6). The signals relative to N-Ts were not

detected. IR (CH2Cl2 solution) CO = 2111 cm-1

.

References

1. K. M. Gillespie, C. J. Sanders, P. O'Shaughnessy, I. Westmoreland, C. P. Thickitt and P.

Scott, J. Org. Chem. , 2002, 67, 3450-3458.

2. B. Castano, T. Pedrazzini, M. Sisti, E. Gallo, F. Ragaini, N. Casati and A. Caselli, App.

Organomet. Chem., 2011, 25, 824-829.

3. A. Caselli, F. Cesana, E. Gallo, N. Casati, P. Macchi, M. Sisti, G. Celentano and S. Cenini,

Dalton Trans., 2008, 4202-4205.

4. A. Berkessel, P. Kaiser and J. Lex, Chem. Eur. J. , 2003, 9, 4746-4756.

5. C. J. Sanders, K. M. Gillespie and P. Scott, Tetrahedron: Asymmetry 2001, 12, 1055-1061.

6. L. Huang, Y. Chen, G.-Y. Gao and X. P. Zhang, J. Org. Chem. , 2003, 68, 8179-8184.

7. Y. Chen, G.-Y. Gao and X. P. Zhang, Tetrahedron Lett., 2005, 46, 4965-4969.

8. C. Böhm, M. Schinnerl, C. Bubert, M. Zabel, T. Labahn, E. Parisini and O. Reiser, Eur. J.

Org. Chem., 2000, 2000, 2955-2965.

9. A. G. M. Barrett, D. C. Braddock, I. Lenoir and H. Tone, J. Org. Chem., 2001, 66, 8260-

8263.

27


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

0.790.81

1.85

2.292.602.73

3.09

4.084.14

7.087.387.427.547.557.627.817.898.02

28


1020

3040

5060

7080

90100

110120

130140

150160

18.418.921.5

30.5

49.050.9

58.2

123.6125.5126.1126.6126.7127.2128.5129.0129.6

29


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

0.770.790.800.831.351.371.821.841.86

2.402.422.47

3.08

4.344.36

5.22

7.247.267.457.527.757.777.797.898.018.04

30


1020

3040

5060

7080

90100

110120

130140

150160

170

18.418.821.523.530.4

47.453.359.0

122.6122.8125.5125.7125.9127.2127.4129.1129.6131.3134.1138.2140.8143.2

31


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

0.820.850.870.891.391.411.831.852.182.202.262.582.612.912.93

4.344.374.394.41

5.09

6.956.97

7.437.557.787.908.15

32


1020

3040

5060

7080

90100

110120

130140

150160

170

18.819.021.423.730.3

48.054.559.3

123.1123.3125.6125.8125.9127.0127.5129.1129.4131.4134.2137.7140.9142.9

33


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

0.510.910.930.960.981.801.821.851.871.891.922.772.792.812.833.003.013.043.053.35

4.254.25

7.427.437.487.617.797.827.877.908.088.10

34


1020

3040

5060

7080

90100

110120

130140

150160

18.819.2

30.4

49.552.1

61.0

123.6125.4126.0126.5128.5129.0

35


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

0.830.850.920.941.551.581.841.861.882.672.682.712.732.812.822.873.313.34

4.644.664.684.70

7.477.597.787.807.887.918.138.16

36


1020

3040

5060

7080

90100

110120

130140

150160

170

18.819.223.130.5

47.853.860.9

122.1122.6122.9125.8125.9126.4128.1129.3131.2134.2139.7

37


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

2.382.662.90

4.00

4.83

7.187.217.267.327.427.497.537.567.617.767.797.857.888.128.15

38


1020

3040

5060

7080

90100

110120

130140

150160

170

21.6

40.8

54.2

123.7125.4126.3127.1129.0129.8132.0134.0136.7143.5

39


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

0.510.54

1.80

2.352.382.55

3.453.804.04

5.00

7.227.257.327.357.387.527.747.767.807.858.18

40


1020

3040

5060

7080

90100

110120

130140

150160

170

16.917.921.6

29.3

54.955.956.9

124.3125.3125.8126.3127.1128.2128.6129.6132.2133.9138.6143.2

41


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

0.18

0.550.56

1.191.211.55

2.412.472.48

3.26

4.564.584.594.614.654.67

7.287.307.397.407.427.457.737.787.807.94

42


1020

3040

5060

7080

90100

110120

130140

150160

170

12.414.819.321.627.6

52.353.656.6

123.9125.0125.1125.5125.6127.3128.2128.8129.7132.1134.1138.0138.2143.4

43


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

0.340.360.670.69

1.461.491.76

2.422.432.48

3.673.69

5.105.125.145.165.365.37

7.237.267.297.377.397.417.437.547.567.587.687.717.727.748.728.75

44


1020

3040

5060

7080

90100

110120

130140

150160

11.115.918.021.7

29.6

48.153.354.7

124.6124.9125.2125.9127.1127.4128.4129.5131.7134.1137.9139.3143.0

45


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

0.640.660.800.82

1.92

2.582.72

3.583.603.624.034.074.194.23

5.04

7.427.587.807.827.857.888.128.15

46


1020

3040

5060

7080

90100

110120

130140

150160

170

16.618.4

29.4

56.357.058.7

117.4121.6123.9125.4126.1126.5128.6128.8128.9132.2133.1134.1

47


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

0.300.32

0.870.891.561.581.681.691.722.632.722.742.772.78

3.56

4.684.854.874.894.91

7.267.467.487.547.787.817.847.878.008.03

48


1020

3040

5060

7080

90100

110120

130140

150160

170

12.414.619.5

27.7

53.253.959.2

117.5121.8123.5125.1125.3125.8125.9128.7129.1132.1134.3137.4

49


0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

8.59.0

2.362.39

3.07

3.93

4.31

7.187.207.237.497.527.767.837.908.108.12

50


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

0.480.570.59

1.19

2.192.29

3.513.643.663.693.723.784.154.204.28

4.694.74

7.017.047.117.297.387.437.537.587.667.757.787.857.888.348.37

51


1020

3040

5060

7080

90100

110120

130140

150160

170

20.220.421.4

30.5

48.953.157.2

65.6

120.2125.0125.4125.7125.9127.7127.8128.0128.5128.9132.7134.0135.7137.2139.3142.3156.5

52


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

0.44

1.561.58

2.332.402.602.63

3.823.94

4.72

5.18

7.057.117.137.447.587.677.707.817.847.898.568.59

53


Alessandro

Font monospazio

in CDCl3

1020

3040

5060

7080

90100

110120

130140

150160

170

21.121.523.830.0

49.550.8

66.5

120.7124.0125.2125.8125.9126.0127.0127.8128.9129.2131.7134.2137.0138.9142.2142.5156.5

54


Alessandro

Font monospazio

in CDCl3

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

0.58

1.391.671.692.02

2.932.98

3.934.024.064.144.594.65

5.355.385.405.42

6.676.706.846.877.037.057.297.387.477.577.667.697.988.008.738.76

55


Alessandro

Font monospazio

in toluene-D8

1020

3040

5060

7080

90100

110120

130140

150160

170

20.821.023.5

30.9

51.4

57.2

66.4

120.5124.5125.2125.9125.9126.3127.2128.2129.0132.5134.9136.3140.4141.9142.7157.4

56


Alessandro

Font monospazio

in toluene-D8

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

0.380.590.61

1.231.341.471.49

2.292.36

3.553.773.86

4.765.01

6.997.097.417.647.767.787.847.867.89

8.54

57


1020

3040

5060

7080

90100

110120

130140

150160

170

20.120.821.4

30.2

49.351.056.0

66.0

120.7124.1125.4126.2126.7127.6127.7128.8128.9132.5134.1137.3139.2141.4142.3156.3

58


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

0.400.691.09

3.053.10

3.853.89

4.474.77

7.077.177.227.277.377.457.667.727.767.78

59


1020

3040

5060

7080

90100

110120

130140

150160

170

19.619.9

29.4

49.953.256.9

125.4126.0126.2128.3128.4129.1136.9

60


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

0.440.73

1.501.521.541.65

2.98

3.833.86

4.374.434.884.945.155.17

7.177.207.407.527.627.687.787.818.42

61


1020

3040

5060

7080

90100

110120

130140

150160

170

19.321.024.029.9

50.450.957.4

69.1

122.1123.6125.3126.0126.4127.2128.9131.6134.2137.9141.2155.1

62


0.51.5

2.53.5

4.55.5

6.57.5

8.59.5

10.511.5

1.841.86

2.452.50

3.443.643.683.744.144.154.204.624.68

5.595.61

7.037.067.217.327.357.427.537.607.627.717.797.81

11.38

63


1020

3040

5060

7080

90100

110120

130140

150160

170

21.721.7

44.446.251.551.752.858.3

122.2122.8127.6127.9129.5129.9130.4130.6132.7133.4134.4139.6144.8145.4155.5156.8

64


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.09.5

10.5

2.032.062.352.493.303.343.493.683.723.904.004.054.094.464.50

6.226.236.817.207.227.367.407.427.447.467.587.727.817.877.93

9.49

10.68

65


1020

3040

5060

7080

90100

110120

130140

150160

170

11.32

21.6021.78

47.1747.7852.9053.4553.7754.3155.17

121.92122.78126.06126.82127.56127.93129.33129.40130.19130.72131.53132.50133.77140.03144.66145.52156.91157.40

66


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.09.5

2.502.582.822.93

3.533.623.68

4.464.864.91

7.177.277.377.427.527.657.757.857.928.058.088.958.99

67


-1.0-0.5

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

-0.47-0.45

0.280.300.660.690.880.91

1.592.102.152.302.372.422.522.572.762.81

3.994.044.584.654.684.73

5.225.29

5.945.96

7.167.237.407.627.697.807.857.887.927.958.678.70

68


1020

3040

5060

7080

90100

110120

130140

150160

170

18.520.321.321.922.424.527.129.9

46.8

55.556.457.157.462.064.7

122.8123.9124.5124.8125.2126.4127.3127.7128.9129.3129.8130.4131.5132.1133.9134.5134.8140.4145.3145.6151.2155.7

69


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0

0.470.801.101.271.52

2.052.072.362.50

2.95

3.50

4.01

4.40

4.70

5.10

6.46

7.207.307.327.637.687.737.757.808.018.158.18

70


1020

3040

5060

7080

90100

110120

130140

150160

170

14.320.821.322.828.831.7

43.6

57.1

121.3122.6125.7127.4128.5130.4131.7139.3

71


0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.09.5

10.5

2.072.092.152.172.282.362.472.562.643.09

3.613.663.954.014.30

4.805.155.215.27

6.186.207.237.397.427.497.527.557.847.877.90

8.758.78

72


1020

3040

5060

7080

90100

110120

130140

150160

170180

190

21.721.923.4

47.550.751.952.755.356.456.8

122.7123.6124.2125.5126.1126.8128.0129.2130.0130.7132.2134.6135.2140.4145.9152.2156.1171.1

184.4

73


Table S1 - Crystal Data and Details of the

Structure Determination of 4f

Crystal Data Formula C43 H52 N4 O4 S2 Formula Weight 753.03 Crystal System Orthorhombic Space group P212121 (No. 19) a, b, c [Angstrom] 11.7359(2) 14.7577(2) 23.1185(3) V [Ang**3] 4004.01(10) Z 4 D(calc) [g/cm**3] 1.249 Mu(MoKa) [ /mm ] 0.180 F(000) 1608 Crystal Size [mm] 0.05 x 0.08 x 0.15 Data Collection Temperature (K) 293 Radiation [Angstrom] MoKa 0.71073 Theta Min-Max [Deg] 1.6, 26.7 Dataset -14: 14 ; -18: 18 ; -27: 28 Tot., Uniq. Data, R(int) 29479, 7762, 0.051 Observed data [I > 0.0 sigma(I)] 5536 Refinement Nref, Npar 7762, 478 R, wR2, S 0.0498, 0.1010, 1.04 w = 1/[\s^2^(Fo^2^)+(0.0395P)^2^+0.1421P] where P=(Fo^2^+2Fc^2^)/3 Max. and Av. Shift/Error 0.00, 0.00 Flack x 0.01(6) Min. and Max. Resd. Dens. [e/Ang^3] -0.25, 0.14


Table S2 - Bond Distances (Angstrom) for 4f S1 -O11 1.432(2) C16 -C33 1.517(5) S1 -O12 1.438(2) C29 -C30 1.523(3) S1 -N3 1.632(2) C29 -C31 1.526(4) S1 -C101 1.760(3) C101 -C102 1.391(4) S2 -O21 1.436(2) C101 -C106 1.375(4) S2 -O22 1.434(2) C102 -C103 1.360(5) S2 -N9 1.624(2) C2 -H2B 0.9700 S2 -C201 1.771(3) C2 -H2A 0.9700 N3 -C2 1.469(3) C103 -C104 1.391(5) N3 -C4 1.494(3) C104 -C105 1.382(5) N6 -C5 1.464(3) C4 -H4 0.9800 N6 -C7 1.474(3) C104 -C107 1.506(5) N6 -C12 1.470(3) C5 -H5A 0.9700 N9 -C8 1.500(3) C105 -C106 1.379(4) N9 -C10 1.474(3) C5 -H5B 0.9700 N12 -C1 1.324(4) C7 -H7B 0.9700 N12 -C11 1.337(4) C7 -H7A 0.9700 C1 -C2 1.518(5) C8 -H8 0.9800 C1 -C403 1.389(5) C10 -H10B 0.9700 C4 -C5 1.553(4) C10 -H10A 0.9700 C4 -C16 1.556(4) C12 -H12 0.9800 C7 -C8 1.537(4) C13 -H13B 0.9600 C8 -C29 1.545(4) C13 -H13C 0.9600 C10 -C11 1.501(4) C13 -H13A 0.9600 C11 -C401 1.379(4) C16 -H16 0.9800 C12 -C13 1.537(3) C17 -H17A 0.9600 C12 -C301 1.527(4) C17 -H17B 0.9600 C16 -C17 1.521(5) C17 -H17C 0.9600 C29 -H29 0.9800 C301 -C310 1.434(4) C30 -H30A 0.9600 C202 -H202 0.9300 C30 -H30B 0.9600 C302 -C303 1.408(4) C30 -H30C 0.9600 C303 -C304 1.348(5) C31 -H31A 0.9600 C203 -H203 0.9300 C31 -H31B 0.9600 C304 -C305 1.403(4) C31 -H31C 0.9600 C205 -H205 0.9300


C33 -H33C 0.9600 C305 -C310 1.423(4) C33 -H33A 0.9600 C305 -C306 1.425(5) C33 -H33B 0.9600 C306 -C307 1.351(6) C201 -C202 1.384(5) C206 -H206 0.9300 C201 -C206 1.372(5) C207 -H20A 0.9600 C102 -H102 0.9300 C207 -H20B 0.9600 C202 -C203 1.373(5) C207 -H20C 0.9600 C203 -C204 1.375(5) C307 -C308 1.391(6) C103 -H103 0.9300 C308 -C309 1.370(5) C204 -C205 1.384(6) C309 -C310 1.418(4) C204 -C207 1.526(5) C401 -C402 1.368(5) C105 -H105 0.9300 C402 -C403 1.367(6) C205 -C206 1.383(4) C302 -H302 0.9300 C106 -H106 0.9300 C303 -H303 0.9300 C107 -H10C 0.9600 C304 -H304 0.9300 C107 -H10D 0.9600 C306 -H306 0.9300 C107 -H10B 0.9600 C307 -H307 0.9300 C107 -H10F 0.9600 C308 -H308 0.9300 C107 -H10E 0.9600 C309 -H309 0.9300 C107 -H10A 0.9600 C401 -H401 0.9300 C301 -C302 1.368(4) C402 -H402 0.9300


Table S3 - Crystal Data and Details of the Structure Determination for: 4d Crystal Data Formula C39 H44 N4 O4 S2 Formula Weight 696.92 Crystal System Orthorhombic Space group P212121 (No. 19) a, b, c [Angstrom] 9.7670(4) 14.2550(5) 25.9891(15) V [Ang**3] 3618.4(3) Z 4 D(calc) [g/cm**3] 1.279 Mu(MoKa) [ /mm ] 0.193 F(000) 1480 Crystal Size [mm] 0.08 x 0.08 x 0.17 Data Collection Temperature (K) 293 Radiation [Angstrom] MoKa 0.71073 Theta Min-Max [Deg] 2.9, 28.9 Dataset -11: 13 ; -19: 10 ; -34: 12 Tot., Uniq. Data, R(int) 12636, 8019, 0.057 Observed data [I > 0.0 sigma(I)] 3437 Refinement Nref, Npar 8019, 442 R, wR2, S 0.0727, 0.1075, 0.97 w = 1/[\s^2^(Fo^2^)+(0.0089P)^2^] where P=(Fo^2^+2Fc^2^)/3 Max. and Av. Shift/Error 0.00, 0.00 Flack x -0.09(10) Min. and Max. Resd. Dens. [e/Ang^3] -0.20, 0.19


Table S4 - Bond Distances (Angstrom) for 4d S1 -O1 1.435(3) C2 -H2 0.9800 S1 -O2 1.436(3) C103 -C104 1.377(8) S1 -N3 1.623(3) C104 -C107 1.501(7) S1 -C101 1.771(5) C4 -H4B 0.9700 S2 -O3 1.444(3) C104 -C105 1.390(8) S2 -O4 1.455(4) C4 -H4A 0.9700 S2 -N9 1.637(4) C105 -C106 1.376(7) S2 -C201 1.771(5) C5 -H5A 0.9700 N3 -C2 1.485(6) C5 -H5B 0.9700 N3 -C4 1.480(6) C7 -H7A 0.9700 N6 -C5 1.471(6) C7 -H7B 0.9700 N6 -C7 1.474(5) C8 -H8B 0.9700 N6 -C311 1.492(6) C8 -H8A 0.9700 N9 -C8 1.481(5) C10 -H10 0.9800 N9 -C10 1.489(7) C21 -H21B 0.9600 N12 -C1 1.335(6) C21 -H21C 0.9600 N12 -C11 1.346(6) C21 -H21A 0.9600 C1 -C2 1.532(6) C22 -H22C 0.9600 C1 -C403 1.370(7) C22 -H22A 0.9600 C2 -C21 1.516(7) C22 -H22B 0.9600 C4 -C5 1.523(6) C201 -C202 1.347(7) C7 -C8 1.515(7) C201 -C206 1.350(9) C10 -C11 1.518(7) C202 -C203 1.379(11) C10 -C22 1.533(7) C102 -H102 0.9300 C11 -C401 1.373(7) C103 -H103 0.9300 C101 -C102 1.377(7) C203 -C204 1.344(10) C101 -C106 1.380(7) C204 -C207 1.500(11) C102 -C103 1.386(7) C204 -C205 1.375(9) C105 -H105 0.9300 C207 -H20C 0.9600 C205 -C206 1.378(11) C307 -C308 1.399(11) C106 -H106 0.9300 C308 -C309 1.376(11) C107 -H10A 0.9600 C309 -C310 1.404(9) C107 -H10C 0.9600 C311 -C312 1.530(7) C107 -H10B 0.9600 C401 -C402 1.383(9) C301 -C310 1.426(7) C402 -C403 1.380(8)


C301 -C302 1.375(7) C302 -H302 0.9300 C301 -C311 1.533(6) C303 -H303 0.9300 C202 -H202 0.9300 C304 -H304 0.9300 C302 -C303 1.401(8) C306 -H306 0.9300 C303 -C304 1.354(11) C307 -H307 0.9300 C203 -H203 0.9300 C308 -H308 0.9300 C304 -C305 1.384(10) C309 -H309 0.9300 C205 -H205 0.9300 C311 -H311 0.9800 C305 -C310 1.436(8) C312 -H31A 0.9600 C305 -C306 1.426(11) C312 -H31B 0.9600 C306 -C307 1.349(11) C312 -H31C 0.9600 C206 -H206 0.9300 C401 -H401 0.9300 C207 -H20A 0.9600 C402 -H402 0.9300 C207 -H20B 0.9600 C403 -H403 0.9300


Table S5 - Crystal Data and Details of the Structure Determination for 5d Crystal Data Formula C37 H41 N4 O4 S2, C F3 O3 S Formula Weight 818.96 Crystal System Orthorhombic Space group P212121 (No. 19) a, b, c [Angstrom] 11.1014(6) 12.1313(7) 29.7535(17) V [Ang**3] 4007.0(4) Z 4 D(calc) [g/cm**3] 1.358 Mu(MoKa) [ /mm ] 0.251 F(000) 1712 Crystal Size [mm] 0.08 x 0.10 x 0.15 Data Collection Temperature (K) 293 Radiation [Angstrom] MoKa 0.71069 Theta Min-Max [Deg] 1.4, 27.0 Dataset -14: 14 ; -15: 15 ; -38: 38 Tot., Uniq. Data, R(int) 33721, 8742, 0.033 Observed data [I > 0.0 sigma(I)] 6124 Refinement Nref, Npar 8742, 473 R, wR2, S 0.0728, 0.2337, 1.00 w = 1/[\s^2^(Fo^2^)+(0.1470P)^2^+1.6658P] where P=(Fo^2^+2Fc^2^)/3 Max. and Av. Shift/Error 0.02, 0.00 Flack x -0.03(11) Min. and Max. Resd. Dens. [e/Ang^3] -0.57, 0.64


Table S6 - Bond Distances (Angstrom) for 5d S1 -O10 1.419(4) F92 -C91 1.31(2) S1 -O11 1.426(4) F92 -C92 1.35(2) S1 -N9 1.637(4) F92 -F923 1.64(2) S1 -C111 1.755(4) F93 -C91 1.31(2) S2 -O20 1.415(5) F93 -F923 1.25(2) S2 -O21 1.425(5) F921 -C92 1.32(2) S2 -N3 1.654(4) F922 -C92 1.32(2) S2 -C211 1.745(5) F922 -C91 1.72(2) S9 -S92 0.517(5) F923 -C91 1.32(2) S9 -O91 1.425(9) F923 -C92 1.32(2) S9 -O92 1.424(5) O91 -O921 0.865(16) S9 -O93 1.424(7) O93 -O923 0.773(14) S9 -O921 1.624(11) N3 -C4 1.459(6) S9 -O923 1.161(10) N3 -C2 1.478(6) S9 -C91 1.785(13) N6 -C5 1.514(5) S92 -O93 1.861(7) N6 -C7 1.501(5) S92 -O921 1.424(11) N6 -C311 1.565(6) S92 -O923 1.425(8) N9 -C8 1.466(6) S92 -C91 1.341(13) N9 -C10 1.465(6) S92 -C92 1.784(15) N12 -C11 1.339(6) S92 -O92 1.425(5) N12 -C1 1.342(6) S92 -O91 1.519(8) N6 -H6 0.9100 F91 -F923 1.40(2) C1 -C403 1.371(7) F91 -F921 1.17(2) C1 -C2 1.500(7) F91 -C92 1.10(2) C4 -C5 1.512(6) F91 -C91 1.316(18) C7 -C8 1.520(6) F92 -F93 1.63(2) C10 -C11 1.509(7) F92 -F922 1.10(2) C11 -C401 1.376(7) C31 -C311 1.523(6) C114 -C117 1.543(8) C31 -C310 1.437(7) C114 -C115 1.408(9) C31 -C32 1.365(7) C115 -C116 1.343(8) C32 -C33 1.409(8) C32 -H32 0.9300 C33 -C34 1.348(10) C33 -H33 0.9300 C34 -C35 1.384(9) C34 -H34 0.9300 C35 -C36 1.414(12) C36 -H36 0.9300 C35 -C310 1.431(7) C37 -H37 0.9300


C36 -C37 1.341(15) C38 -H38 0.9300 C37 -C38 1.443(15) C39 -H39 0.9300 C38 -C39 1.370(10) C211 -C216 1.370(9) C39 -C310 1.395(8) C211 -C212 1.394(9) C2 -H2A 0.9700 C112 -H112 0.9300 C2 -H2B 0.9700 C212 -C213 1.400(8) C4 -H4A 0.9700 C113 -H113 0.9300 C4 -H4B 0.9700 C213 -C214 1.371(11) C5 -H5B 0.9700 C214 -C215 1.352(11) C5 -H5A 0.9700 C214 -C217 1.523(8) C7 -H7B 0.9700 C115 -H115 0.9300 C7 -H7A 0.9700 C215 -C216 1.369(8) C8 -H8B 0.9700 C116 -H116 0.9300 C8 -H8A 0.9700 C117 -H11A 0.9600 C10 -H10A 0.9700 C117 -H11B 0.9600 C10 -H10B 0.9700 C117 -H11C 0.9600 C111 -C112 1.394(7) C91 -C92 0.71(2) C111 -C116 1.395(7) C311 -C312 1.519(7) C112 -C113 1.368(8) C212 -H212 0.9300 C113 -C114 1.339(9) C213 -H213 0.9300 C215 -H215 0.9300 C311 -H311 0.9800 C216 -H216 0.9300 C312 -H31B 0.9600 C217 -H21C 0.9600 C312 -H31C 0.9600 C217 -H21A 0.9600 C312 -H31A 0.9600 C217 -H21B 0.9600 C401 -H401 0.9300 C401 -C402 1.346(8) C402 -H402 0.9300 C402 -C403 1.381(8) C403 -H403 0.9300


Asymmetric cyclopropanation of olefins catalysed by Cu(I ... · -mail: [email protected]...

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