Ringcontraction%reactions in% Total%synthesis · 01.10.14 1 1 Ringcontraction%reactions in%...

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1

Ring contraction reactions in

Total synthesis

Ruben Eckermann Gaich-Group Seminar

October 2nd, 2014

Gaich-‐Group Seminar Ruben Eckermann Overview

2

Exclusion of one heteroatom One-carbon contraction

-  Eschenmoser contraction -  Ramberg-Bäcklund reaction

-  Photo-Fries rearrangement

-  Wittig rearrangement

-  Stevens rearrangement -  Co-mediated O à C – contraction

-  Zr-mediated O à C – contraction

à mostly used for macrocycles

-  Wager-Meerwein/Pinacol rearrangements

-  Epoxide rearrangement

-  Favorski rearrangement

-  oxidative contractions -  Wolff rearrangement à  mostly used for cyclopentyl units à  Review: L. F. Silva, Jr. Tetrahedron

2002, 58, 9137-9161

Y- Y

01.10.14

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Gaich-‐Group Seminar Ruben Eckermann

3

Exclusion of one heteroatom

Y- Y


4

Eschenmoser sulfide contraction

Synthesis of 1,3-dicarbonyls via S-alkylation:

SH

O

XO

n

base

PR3

S

O

OHn

S

OH

On

- S=PR3

OOH

n

X = I, Br, Cl, OTs, OMs S

HN

X

O base

PR3n N

SOH

nHN

SO

n HN

O

n

- S=PR3

X = I, Br, Cl, OTs, OMs

S

HNHN

n

BPO

then PR3

S

NHN

n

OR

N

SHN

nHN

SN

n HN

N

n

- S=PR3

S

HN

I

N base

PR3n N

SHN

nHN

SN

n HN

N

n

- S=PR3

S

HNHN

n

NIS

via enamine prefunctionalization:

via oxidation of sulfur:

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5

Vitamin B12 synthesis

A. Eschenmoser, C. E. Winter, Science 1977, 196, 1410 - 1420

NH

SO S

Me

Me

CO2Me

NH

OMe

Me

CO2Me

+

a) BPO, HCl (CH2Cl2) then P(OEt)3 (xylene), 125°C

43%

N

S

O

MeMe

H

CO2MeHN

MeMeS

H

CO2Me

N

Br

Me

NC

CO2Me

a) KOtBu (THF/tBuOH)b) P(CH2CH2CN)3 TFA, (sulfolane) 60°C

64%

N

MeH

CO2Me

HN

MeMe

H

CO2Me

N

Me

MeO2C

CN

a) NIS, (CH2Cl2), 0°C then

c) HNEt2 (MeOH)

CONEt2

NH

S

Me

MeNC

MeO2C

CO2Me

NaHMDS, (PhH/tBuOH)then Cd(ClO4)2, (MeOH)

N

MeH

CO2Me

N

MeMe

H

CO2Me

N

Me

MeO2C

CN

CONEt2

S

N

Me

MeNC

MeO2C

MeO2C

(Cl)Cd

1 23

4

56

7


6

Vitamin B12 synthesis

A. Eschenmoser, C. E. Winter, Science 1977, 196, 1410 - 1420

then PPh3, TFA(PhH), 80°C

46%

N

MeH

CO2Me

N

MeMe

H

CO2Me

N

Me

MeO2C

CN

CONEt2

N

Me

MeNC

MeO2C

MeO2C

(Cl)Cd

7

a) DBU, (sulfolane) 60°C then HOAc, Cd(ClO4) (MeOH)

b) hυ, visible (MeOH), 60°c) CoCl2, 58°C then KCN, O2, H2O (CH2Cl2), 0°C

46%

N

MeH

CO2Me

N

MeMe

H

CO2Me

N

Me

MeO2C

CN

CONEt2

N

MeMeO2C

MeO2C

8

HMe Co

CN

CN

N

MeH

CONH2

N

MeMe

H

CONH2

N

Me

H2NOC

CO2-

CONH2

N

MeH2NOC

H2NOC

Cobyric acid (9)

HMe Co

CN

CN

Me

Me

6

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7

1β-Methylcarbapenem

O. Sakurai, T. Ogiku, M. Takahashi, M. Hayashi, T. Yamanaka, H. Horikawa, J. Org. Chem. 1996, 61, 7889 - 7894

NHO

H HCO2H

TBSO a) CDI, HSCO2Et

CO2Et

b) HO

HO

O

O80%

NO

H HTBSO

S

OCO2Et

CO2Et

OH

O O

SOCl2, pyrthen iPr2NH

75% NO

H HTBSO

S

O

OO

a) NaH, PPh3 then (PhO)2POCl

b) iPr2NHHS

HN O

O66%

NO

H HTBSO

S

OO HN

O

O

10 11 12

13

NO

H HHO

S

OOH NH2

1β-Methylcarbapenem

6

5


8

Ramberg-Bäcklund rearrangement

S

X

n

baseS

n

O

O

O

O

heatn


X

nSH

baseS

noxidation

Sn O

O

base

X+

via S-alkylation/oxidation:

via cycloaddition:

SO O

Cr(CO)3

+

hυ [6π+4π]then CO SO2

base

X+SO2

X

baseSO2

-SO2

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9

(+)-Fawcettidine

J. A. Kozak, G. R. Dake, Angew. Chem. Int. Ed. 2008, 47, 4221 - 4223

O

(+)-pulegone (14)

a) H2O2, LiOHb) NaH, HSPh

c) NaBO3, AcOH84%

OSO

Ph

15

DBU, (DMF), -40°Cthen CO2Me

then 40°C63%

O

16

CO2Me

a) BrMgCH2CH2CCTMS CuBr*SMe2, (THF) -78 to -40°C

b) TBAF, (THF)80%

O

17

CO2Me

SEtHN

ONH3

CF3CO2-

a) AcOH, (PhMe), 110°C

b) PtCl2 (10mol%) (PhMe), 90°Cc) SeO2, (1,4-dioxane) 85°C

33%18

N

O

HO

SEtHN

O

a) 1 M NaOHb) ethylene glycol PPTS, (PhH)

then mCPBA(CH2Cl2)

85%

N

O

H

Me

S

O

OH

H

19

O

Oa) CBr2F2, KOH (CH2Cl2/tBuOH)b) H2, Pd/C, (EtOH/THF)

then LiAlH4then 1 M HCl

11%

N

H

Me HH

(+)-fawcettidine (20)

O

8 7


10

(+)-Estradiol

J. H. Rigby, N. C. Warshakoon, A. J. Payen, J. Am. Chem. Soc.. 1999, 121, 8237 - 8245

Me O

OH

CO2H

Me OTBS

H

SO O

a) (TMSCCH)Co2(CO)6 (PhMe), refluxb) Br2, NEt3

c) (MeCN)3Cr(CO)3 (THF)

18%

S

TMS

O O

Cr(CO)3

Me OTBS

HSO2

TMS

1) hυ2) CO

70%

a) KOtBu, -105°C then NCSb) KOtBu, -105°C

65%

TMS

Me OTBS

H H

a) KNH(CH2)3NH2 (THF), rtb) HF, (MeCN)

c) Et3SiH, TFA27%

TMS

Me OH

H H

H Pb(OTFA)4, TFA

80%

HO

Me OH

H H

H

2122

2324

25 26

27 (+)-estradiol (28)

77

66

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11

Photo-Fries rearrangement

HO

CO2Hn

OO

ncoupling hυ

OO

n

OO

n

OO

n

HOO

n

HOO

n


12

Kendomycin

H. J. Martin, T. Magauer, J. Mulzer, Angew. Chem. Int. Ed. 2010, 49, 5614 - 5626

MeOMe

MOMO

O

HO2C

Me

+Me

OH

OTBDPS

29 30

a) EDCI, DAMP

b) LDA, TBSCl71%

Me

OMeMOMO

O

MeOH

OMe

OTBDPS

31

a) LiAlH4b) MsCl

c) LiAlH494% Me

OMeMOMO

O

Me

MeMe

OTBDPS

32

a) TBAFb) IBXc) Sn(OTf)2, 33

d) NMe4BH(OAc)3e) LiOH, H2O2

52% Me

OMeMOMO

O

Me

MeMe

O

34

O

Me

HOMe N O

Bn

OOO

Me33

a) HClb) Me2C(OMe)2, CSA

c) LiOH71% Me

OMeHO

O

Me

MeMe

35

OMe

OMe

CO2H

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13

Kendomycin

H. J. Martin, T. Magauer, J. Mulzer, Angew. Chem. Int. Ed. 2010, 49, 5614 - 5626

Me

OMeO

O

Me

MeMe

36

OMe

OMe

EDCI, DMAP DMAP*HCl

hυ, 254 nm (cyclohexane)

41%

O

Me

OMe

O

Me

MeMe

37

OMe

HOO

O

Mea) NaBH4, HClb) TsOH

71%Me

OMe

O

Me

MeMe

38HO

O

HO

Me

Me

a) TESOTfb) IBX

61%Me

O

O

Me

MeMe

39O

O

TESO

Me

Me

aq. HF

50%

Me

O

O

Me

MeMe

kendomycin (40)

HO

O

HO

Me

Me

OH

20 18


14

Wittig rearrangement

[1,2] - rearrangement:

OH

EWG

X


baseO

EWGn

nbase

O

EWG

n[1,2]

EWG

OHn


OH

EWG

X


baseO

EWGn

nbase

EWG OH

nO

EWG

n[2,3]

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15

Kallolide A ring system

HO

TBDPSO

Ph3PCO2Me

a) Swernb)

c) DIBAL-Hd) Swerne) CBr4, PPh3

63%

BrBr

Me

TBDPSO

a) BuLi, CH2Ob) mCPBA

62%

HO Me

TBDPSO

O a) Me2CuLi/LiAlH4 (THF), -78°Cb) TBSCl

52%

O

Me

CH

TBSO

Me

HO

TBDPSO

HO

TBDPSO

a) AgNO3, (ac)b) PPTS (ethanol)

79%

Ph3PCO2Me

a) Swernb)

c) DIBAL-Hd) DHPe) TBAF

O

Me

HO

MeTHPO

72%

a) TsClb) LiCCH, (DMSO)c) BuLi, CH2O

d) MsCl, lutidine then LiCle) PPTS, (EtOH)f) EtMgBr, (THF/HMPA)

52%

O

MeMe

O

41 42 43 44

45 46 47

J. A. Marshall, B. Yu, J. Org. Chem. 1994, 59, 324 - 331


16

Kallolide A ring system

J. A. Marshall, B. Yu, J. Org. Chem. 1994, 59, 324 - 331

O

MeMe

O

47

O

Me

OH

O

Okallolide A (53)

68%

BuLi, -78°C(THF/pentane)

O

Me

48

HOO

Me

49

HO+

7:3

a) Ac2Ob) MnO2

83%O

Me

50

AcO

MnO244%

O

Me

O

51

Me

E/Z = 2:3

53%

BuLi, -78°C(THF/pentane) O

Me

52

HO

15

15 12

12 12

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17

Stevens rearrangement

N

EWG

X


baseN

EWGn

nbase

N

EWG

n[1,2]

EWG

Nn



N

EWG

X


baseN

EWGn

nbase

EWG N

nN

EWG

n[2,3]

N

EWG

N2

n N

EWG

nRh2(OAc)4

via diazo-compound:


18

(±)-Desoxycodein-D

J.-P. Liou, C.-Y. Cheng, Tet. Lett. 2000, 41, 915 - 918

N

OAca) MeI, (CH2Cl2)b) NaBH4, (MeOH) 0°C

c) EtO2CCl, KHCO3 (ClCH2Ch2Cl), refluxd) NaOH, (MeOH), 0°C

73%

N

OH

CO2Et

CHO

MeO

BrHO

a) DEAD, PBu3, (THF)

b) NaBH4, (MeOH) 0°Cc) TBSCl, imidazoled) Pd(OAc)2, PPh3, NEt3 (MeCN), 130°C

45%

N

O

CO2Et

MeO

OTBS

a) TBAF, (THF)b) NCS, PPh3, (THF)

c) Pd(PPh3)4, NEt3 (MeCN), 130°C

54% N

O

MeO

MeI, (CH2Cl2)

N

O

MeO

Me

PhLi, (Et2O), 0°C

83%

N

O

MeO

Me

54 55

56

57

58 59 Desoxycodeine-D (60)

7 6

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19

Co - mediated O à C contraction

S. J. Meek, F. Pradaux, E. H. Demont, J. P. A. Harrity, Org. Lett. 2006, 8, 5597 - 5600

OR1

PPh3BF4

R2

R3O

a) nBuLi, -78°C (THF)

b) Co2(CO)8, (CH2Cl2)c) PPTS, (CH2Cl2)

OR1

R3

R2

3 eq. Et2AlCl(CH2Cl2) -78 to -30°C

OR3

R2LAR1

OR3

R2

R1

Co2(CO)6Co2(CO)6

(CO)6Co2

CAN, MeOH, 0°C

OR3

R2

R1

6

4


20

Co - mediated O à C contraction

Substrate scope:

O

Ph

O

TMS

O

OTBDPS

O

Bu

O

OTBDPS

OPh

OTBDPS

O

OTBDPS

OPh

TMS

O

TMS

O

Ph

O

TMS

O

OTBDPS

O

Ph Ph

O

O

TMS89% 84% 78% 86%

68% 71%78%

73%

75% 82%

49% 50% 49%80%

68%

61 62 63 64 65

66 67 68 69 70

71 72 73 74 75

S. J. Meek, F. Pradaux, E. H. Demont, J. P. A. Harrity, Org. Lett. 2006, 8, 5597 - 5600

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21

Zr - mediated O à C contraction

carbo-hydrate

O OMe

Cp2ZrCl2, nBuLiBF3*OEt2, (PhMe)-78 °C to rt

O OMe

ZrCp2

O

ZrCp2

OH

5

4


22

Zr - mediated O à C contraction

a)  L. A. Paquette, X. Peng, J. Yang, Angew. Chem. Int. Ed. 2007, 46, 7817 – 7819 b) L. A. Paquette, G. D. Parker, T. Tei, S. Dong, J. Org. Chem. 2007, 72, 7125 – 7134 c) L. A. Paquette, R. M. Arbit, J.-A. Funel, S. Bolshakov, Synthesis 2002, 14, 2105 – 2109 d) J. D. White, S. Jana, J. Org. Chem. 2014, 79, 700 - 710

O

OH

HOHO

OHOH

D-glucose (76)

O OMe

OPMB

TBDPSOCp2Zr OH

OPMB

OTBDPS

60%

O

OMe

Me

Cp2Zr63%

HOMe

O OMe

OTBS

PMBO

OH

OTBS

PMBO

Cp2Zr

86%

7778

79

80

81

82

O OMe

MeMeBnO

Cp2Zr74%

OHMeMe

BnO

83 84

O

OH

O

O H

MeMe

MeH

MeMe OH Me

MeMe O

H H

OMe

OH

AcO

O

CO2Me OH

OAc

O

O

O

O

Providencin (85)

(+)-Epiafricanol (86)Pestalotiopsin A (87)

(+)-Fomannosin (88)

01.10.14

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23

One-carbon contraction


24

Wagner – Meerwein / Pinacol rearrangement

-  rearrangement of cationic intermediates -  mostly ring contraction / expansion sequence

Wagner – Meerwein rearrangement:

Pincaol rearrangement:

XMe Me

- X- - H+

n n n n

HOOTs

- OTs-

HOOH O

- H+

n n n n

01.10.14

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25

(±) - Bulnesol

J. A. Marshall, J. J. Partridge, Tetrahedron. 1969, 25, 2159 - 2192

EtO2C

O

OHHOa) H+

b) LiAlH4

c) MsCld) NaOPh (THF), reflux

OPh

O

O

a) H+

b) BF3*OEt2, (Et2O)CO2Et

N2

c) NaOEt O

d) H2SO4

O

H

CO2Et

PhO

a) OH-

b) LiAlH4 (DME), reflux

a) Li, NH3b) H3O+

c) Ac2O, py

HO

H

Me

PhO

d) MsCl, pye) H2, Pt Me

MsO

H

Me

AcO

HOAcNaOAc

MeH

a) CrO3b) CH2N2

c) NaOMed) MeLi

MeHMeMe OHOH

8990 91 92

93 94 (±) - Bulnesol (95)

65

c) TsCl, pyrd) LiAlH4 (DME), reflux


26

2-norCedrene

H. K. Hariprakasha, G. S. R. SubbaRao, Tet. Lett. 1997, 38, 5343 - 5346

MeO

NCCl a) KOH, 55°C

(DMSO/H2O)

b) BF3, MeOH (CH2Cl2)

78%

O

MeO

a) Pd/C, limoneneb) NaH, MeI, 60°C (DME)

c) NaBH4, 0°C (MeOH)

90%

HO

MeO

Me Me

BF3*OEt2(PhH), reflux

87%HMe Me

O a) MeLi, (Et2O) 0°C to reflux

b) POCl3, py, 0°C then HI, (PhH)

80%HMe Me

96 9798

99 2-norCedrene (100)

6

5

01.10.14

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27

Epoxide rearrangement

O OLA

CHOepoxidation LA

n nn

n


28

β – Microbiotene & Microbiotol

a) A. Srikrishna, S. A. Nagamani, J. Chem. Soc., Perkin Trans. 1. 1999, 3393 – 3394 b) A. Srikrishna, D. B. Ramachary, Tet. Lett. 1999, 40, 6669 - 6670

OMe Meβ - ionone (101)

a) NaOH, Br2 (dioxane), 0°C then H2SO4, (MeOH) reflux

b) mCPBA, NaHCO3 (CH2Cl2), 0°C

93%

O

Me

MeMeOMe

O

BF3*OEt2(CH2Cl2), -78°C

90% Me Me

Me

O

O

OMe

a) H2, Pd/C, (EtOH)

b) TiCl4, CH2Br2 Zn, (CH2Cl2), 0°C

60%

Me Me

MeO

OMe

a) NaOH, (THF/H2O) refluxb) (COCl)2, (PhH)

c) CH2N2, (Et2O), 0°Cd) Cu-CuSO4, (cC6H12) W-lamp, reflux

74%

Me Me

Me

OMe Me

Me

O

+

1 : 1.7

Ph3P+MeI-, NaOAm(PhH)

75% Me Me

MeMeMgI, (Et2O)

75%Me Me

Me

MeOH

102 102

104 105 106

106 106

β - Microbiotene (107) Microbiotol (108)

6 5

01.10.14

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29

Favorski rearrangement

OX

X = Cl, Br, I, OTs

baseO

Nuc-H

Nuc

O

n nn

Favorski rearrangement:

Homo-Favorski rearrangement:

O

X

X = Cl, Br, I, OTs

O Nuc

O

n n n

baseNuc-H


30

ex (+) - Pulegone

L. F. Silva, Jr., Tetrahedron 2002, 58, 9137 - 9161

Me

O

a) Br2, (Et2O)

b) NaMeO, (MeOH)67%

CO2Me

Me

O

Me H

HO O

Me H

HO

Me

Me H

HO

MeMe

HMe

Me

Me

Me

MeO

O

(+) - Pulegone (109) 110

(-) - Mitsugashiwalactone (111)

(-) - Iridomyrmecin (112)

(+) - Epoxydictymene (113)

(+) - Acoradiene (114)

(-) - Acorone (115)

6 5

01.10.14

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31

Cubane

P. E. Eaton, T. W. Cole, Jr., J. Am. Chem. Soc. 1964, 86, 962 & 3157

O

a) NBS, (CCl4)b) Br2, 0°C (CH2Cl2/pentane)

c) Et2NH, (Et2O) -20°C

40%

OBr

Br

O

a) (CH2OH)2, pTSA (PhH), refluxb) HCl conc.

c) hυ, (PhH)85%

OBrO

O10% KOH

95% BrO

O

HO2C

a) SOCl2b) tBuOOH, py (Et2O)

c) 152°C, (cumene)d) 75% H2SO4

47%

Br

O 25% KOH

55%CO2H

a) SOCl2b) tBuOOH, py, (Et2O)

c) 150°C (diisopropylbenzene)

29%

116 117 118 119

120 121 Cubane (122)

Br

5 4

5 4


32

Oxidative contractions

Thallium (III) – promoted:

Lead (IV) – promoted: O OH

Pb(OAc)4 Pb(OAc)3HO

ROHHO OR

Pb(OAc)3CO2R

n n n n n- Pb(II)

Iodine (III) – promoted:

O OHTl(NO3)3 Tl(NO3)2

HOROH

HO ORTl(NO3)2

CO2R

n n n n n- Tl(I)

O OHHTIB I(Ph)OHHO

ROHHO OR

I(Ph)OHCO2R

n n n n n

IOH

OTsHTIB =

- PhI


01.10.14

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33

Thallium (III) - promoted

a) V. M. T. Carneiro, H. M. C. Ferraz, T. O. Vieira, E. E. Ishikawa, L. F. Silva, Jr., J. Org. Chem. 2010, 75, 2877 – 2882 b) G. G. Bianco, H. M. C. Ferraz, A. M. Costa, L. V. Costa-Lotufo, C. Pessoa, M. O. de Moraes, M. G. Schrems, A. Pfaltz, L. F. Silva, Jr. J. Org. Chem. 2009, 74, 2561 – 2566 c) I. R. M. Tébéka, G. B. Longato, M. V. Craveiro, J. E. de Carvalho, A. L. T. G. Ruiz, L. F. Silva, Jr., Chem. Eur. J. 2012, 18, 16890 - 16901

Me

MeOMe Tl(NO3)3, (MeCN)

MS 3Å, 0°C

96%

MeO

Me

Me

CHO

a)PPh3

b) NaSEt, (DMF)56%

HO

Me

Me

NBoc

Me

Tl(NO3)3, (MeCN)then NaBH4

50% NBoc

MeHO

a) TsCl, py NEt3, (CH2Cl2)

b) NaBH4, (DMSO)70%

NBoc

Me

Me

123 124 (-) - Mutisianthol (125)

126 127 (+) - trans - Trikentrin A (128)

O

MeMe Tl(NO3)3, (MeOH)

TMOF, rt

59%

MeMe

MeO2C

a) H2, Pd/Cb) KOH, MeOH

c) MeLi86%

MeMe

O

HMDS, TMSIthen MeLithen CNCO2Me

64%

MeMe

MeO2C

O129 130 131 (+) - Bakkenolide A (132)

6 5

6 5

6 5


34

Lead (IV) - promoted


OMe

O MeO

O

13% 65%

54% 55%

Pb(OAc)4CH(OEt)3

HClO4

Pb(OAc)4CH(OEt)3

HClO4

Pb(OAc)4CH(OEt)3

HClO4

Pb(OAc)4CH(OEt)3

HClO4

CO2EtCO2Et

Me

CO2EtMe

CO2Et

129 130 131 132

133 134 135 136

5 4 6 5

7 6 8 7

O BF3*OEt2, (MeOH)then Pb(OAc)4, (PhMe)

43%

CO2Me

Bn Ph

HNO Ph

137 138 139

6 5

EtOO

Me

MeH

Me

O

Pb(OAc)4, BF3(PhH/EtOH)

80%O

Me

HMe

O

Me

EtO2C

140 141

6 5

01.10.14

18


35

Iodine (III) - promoted


O

Ar

nn = 1-3

PhI(OAc)2, CH(OEt)3HClO4

62 - 74%

CO2Et

Arn

O Ph

O

PhI(OAc)2, TMOF[H2SO4]

39%

OPh

CO2Me

142 143 144 145

6 5

Me

Me OH

HO

PhI)OAc)2, KOH(MeOH) then HCl

65%

Me

Me OH

H

MeO2C

146 147

6 5

PhIO*BF3(CH2Cl2), -15°C

60%CHO

O

PhIO*BF3(CH2Cl2), -15°C

36% OCHO

148 149

150 151

6 5

6 5

O

O

OHPhI(OAc)2(CH2Cl2), 0°C

91%

O

O

O

IPh

MeCN

reflux 55%

O

O

C OH2O

O

O

152 153 154 155

6 5


36

(±) - Indatraline

L. F. Silva, Jr., F. A. Siqueira, E. C. Pedrozo, F. Y. M. Vieira, A. C. Doriguetto, Org. Lett. 2007, 9, 1433 - 1436

O

ClCl

a) NaBH4b) pTsOH

91%

ClCl

HTIBMeOH

62%

MeOOMe

Cl

Cl

a) Jones ox.b) SOCl2 then NH3

80%

NH2

Cl

Cl

O

PIFA

90%

NH2

Cl

Cl

a) Boc2Ob) NaH, MeI

c) MeOH, AcCl83%

NH*HCl

Cl

Cl

156 157 158 159

160 (±) - Indatraline (161)

65

01.10.14

19


37

Wolff rearrangement

Odiazotransfer

n

O

n

N2 [M] or hυ

- N2

O

n

CO

NuH

ONu

n n


38

(±) – Δ9(12) - Capnellene

M. Ihara, T. Suzuki, M. Katogi, N. Taniguchi, K. Fukumoto, J. Chem. Soc., Chem. Commun. 1991, 646 - 647

Me Me

O

a) CH2=CHMgBr, CuI (TMEDA) then CNCO2Me, HMPAb) HSCH2CH2SH, BF3*OEt2

c) cHex2BH then H2O2 NaOHd) Ra/Ni

73%

Me Me

CO2Me

OH

a) CSA, (PhH) refluxb) LDA, MeIc) DIBAL-H

d) Swerne) CH2=CHMgBrf) DMP

52%

Me Me O

O

H

Me

a) KOtBu, TBSCl (THF), -78°Cb) DBU

30%

Me Me OTBS

O

H

MeH

H

a) NaBH4b) TBAF

c) NaOMe, HCO2Etd) TsN3, NEt3

92%

Me Me O

HO

H

MeH

H

N2hυ, (MeOH)

48%

Me Me

HO

H

MeH

CO2Me

a) TBSOTf, DMAP 2,6-lutidineb) DIBAL-H

c) MsCl, NEt3d) o-NO2PhSeCN NaBH4 then H2O2

69%

Me Me

TBSO

H

MeH

H

a) TBAFb) NaH, CS2, imidazole then MeI

c) Bu3SnH, AIBN (PhMe)24%

Me MeH

MeH

H

162163 164

165 166 167

168 (±) - Δ9(12) - Capnellene (169)

H

6 5

01.10.14

20


39

Salvilenone

R. L. Danheiser, A. L. Helgason, J. Am. Chem. Soc. 1994, 116, 9471 - 9479

O

Me

a) Br2, AlCl3b) Ph3P=CH2, (THF)

c) Tl(NO3)3, MeOH35%

BrO

Me

TrN3, KOH[Bu4NBr], 18-c-6(H2O/PhH)

88%

BrO

Me

N2

OSi(iPr)3

hυ (vycor)(ClCH2Ch2Cl)rt then 80°C

71%

Br

Me

CO

Br

Me

O OSi(iPr)3Br

Me

CO

OSi(iPr)3

Br

HO OSi(iPr)3

Me

a) MeLi, (THF) then nBuLi then acetone -78°C to rt then HCl, MeOH refluxb) TBAF, (THF)c) DDQ, (PhH)

43%Me

OO

170 171 172

173 174 175

176 Salvilenone (177)

7

6

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