Supporting Information OOene Pot SySy es snthesis ofAmino ... · Ring Opening Sequences†...

Supporting Information

One Pot Synthesis of Amino Acids Derived Chiral DisubstitutedO e o Sy es s o o c ds e ved C subs u edMorpholines and 1,4-Oxazepanes via Tandem Aziridine/EpoxideRing Opening Sequences†

Krishnananda Samanta and Gautam Panda*Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow-226001, UP, India

E-mail : [email protected] Tel : 91-522-2612411-18, Ext. 4385, 4603 Fax: 91-522-2623405

1. Contents 1-4

2 S t 5 612. Spectra 5-61

Fig. S-1: 1H Spectra of (S)-2-iso-Propyl-1-tosylaziridine 4.

Fig. S-2: 13C Spectra of (S)-2-iso-Propyl-1-tosylaziridine 4.

Fig. S-3: 1H Spectra of (S)-2-iso-Butyl-1-tosylaziridine 12a.

Fig. S-4: 13C Spectra of (S)-2-iso-Butyl-1-tosylaziridine 12a.

Fig. S-5: 1H Spectra of (S)-3-((1-Tosylaziridin-2-yl)methyl)-1H-indole 12c.

Fig. S-6: 13C Spectra of (S)-3-((1-Tosylaziridin-2-yl)methyl)-1H-indole 12c.

Fig. S-7: 1H Spectra of (S)-2-Methyl-1-tosylaziridine 12d.

Fig. S-8: 13C Spectra of (S)-2-Methyl-1-tosylaziridine 12d.

Fig. S-9: 1H Spectra of inseparable mixture of 6 & 7.

Fig. S-10: 13C Spectra of inseparable mixture of 6 & 7.

Fig. S-11 : 1H Spectra of mixtures of 8 and 9 . 1

Electronic Supplementary Material (ESI) for Organic and Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2011

Fig. S-12 : 13C Spectra of mixtures of 8 and 9 .

Fig. S-13: 1H Spectra of (3S,5S)-3-((tert-butyldimethylsilyloxy)methyl)-5-isopropyl-4-tosylmorpholine 8.

Fig. S-14: 1H Spectra of (3S,6S)-3-iso-Propyl-4-tosyl-1,4-oxazepan-6-ol 7.

Fig. S-15: 13C Spectra of (3S,6S)-3-iso-Propyl-4-tosyl-1,4-oxazepan-6-ol 7.

Fig. S-16: HPLC Spectra of (3S,6S)-3-iso-Propyl-4-tosyl-1,4-oxazepan-6-ol 7.

Fig. S-17: 1H Spectra of (3S,5S)-5-iso-Propyl-4-tosylmorpholin-3-yl)methanol 6.

Fig S-18: 13C Spectra of (3S 5S)-5-iso-Propyl-4-tosylmorpholin-3-yl)methanol 6Fig. S-18: C Spectra of (3S,5S)-5-iso-Propyl-4-tosylmorpholin-3-yl)methanol 6.

Fig. S-19: 1H Spectra of (3S,5S)-5-iso-Propyl-4-tosylmorpholin-3-yl)methyl methanesulfonate 10.Fig. S-20: 13C Spectra of (3S,5S)-5-iso-Propyl-4-tosylmorpholin-3-yl)methyl methanesulfonate 10.

Fig. S-21: HPLC Spectra of (3S,5S)-5-iso-Propyl-4-tosylmorpholin-3-yl)methyl methanesulfonate 10.

Fig. S-22: 1H Spectra of (3S,6S)-3-iso-Butyl-4-tosyl-1,4-oxazepan-6-ol 14a.

Fig. S-23: 13C Spectra of (3S,6S)-3-iso-Butyl-4-tosyl-1,4-oxazepan-6-ol 14a.

Fig. S-24: HPLC Spectra of (3S,6S)-3-iso-Butyl-4-tosyl-1,4-oxazepan-6-ol 14a.

Fi S 25 1H S t f (3S 6S) 3 B t l 4 t l 1 4 6 l 14bFig. S-25: 1H Spectra of (3S,6S)-3-sec-Butyl-4-tosyl-1,4-oxazepan-6-ol 14b.

Fig. S-26: 13C Spectra of (3S,6S)-3-sec-Butyl-4-tosyl-1,4-oxazepan-6-ol 14b.

Fig. S-27: HPLC Spectra of (3S,6S)-3-sec-Butyl-4-tosyl-1,4-oxazepan-6-ol 14b.

Fig. S-28: 1H Spectra of (3S,6S)-3-((1H-Indol-3-yl)methyl)-4-tosyl-1,4-oxazepan-6-ol 14c.Fig. S 28: H Spectra of (3S,6S) 3 ((1H Indol 3 yl)methyl) 4 tosyl 1,4 oxazepan 6 ol 14c.

Fig. S-29: 13C Spectra of (3S,6S)-3-((1H-Indol-3-yl)methyl)-4-tosyl-1,4-oxazepan-6-ol 14c.

Fig. S-30: HPLC Spectra of (3S,6S)-3-((1H-Indol-3-yl)methyl)-4-tosyl-1,4-oxazepan-6-ol 14c.

Fig. S-31: 1H Spectra of (3S,5S)-3-((tert-butyldimethylsilyloxy)methyl)-5-methyl-4-tosylmorpholine.

Fig. S-32: 13C Spectra of (3S,5S)-3-((tert-butyldimethylsilyloxy)methyl)-5-methyl-4-tosylmorpholine.

Fig. S-33: 1H Spectra of (3S,6S)-3-methyl-4-tosyl-1,4-oxazepan-6-ol 14d.2


Fig. S-34: Expanded 1H Spectra of (3S,6S)-3-methyl-4-tosyl-1,4-oxazepan-6-ol 14d.

Fig. S-35: 13C Spectra of (3S,6S)-3-methyl-4-tosyl-1,4-oxazepan-6-ol 14d.

Fig. S-36: DEPT Spectra of (3S,6S)-3-methyl-4-tosyl-1,4-oxazepan-6-ol 14d.

Fig. S-37: COSY Spectra of (3S,6S)-3-methyl-4-tosyl-1,4-oxazepan-6-ol 14d.

Fig. S-38: Expanded COSY Spectra of (3S,6S)-3-methyl-4-tosyl-1,4-oxazepan-6-ol 14d.

Fig. S-39: NOESY Spectra of (3S,6S)-3-methyl-4-tosyl-1,4-oxazepan-6-ol 14d.

Fig. S-40: Expanded NOESY Spectra of (3S,6S)-3-methyl-4-tosyl-1,4-oxazepan-6-ol 14d.

Fig. S-41: HPLC Spectra of (3S,6S)-3-methyl-4-tosyl-1,4-oxazepan-6-ol 14d + 13a.

Fig. S-42: HPLC Spectra of (3S,6S)-3-methyl-4-tosyl-1,4-oxazepan-6-ol 14d.

Fig. S-43: 1H Spectra of ((3S,5S)-5-methyl-4-tosylmorpholin-3-yl)methanol 13a

Fig. S-44: 13C Spectra of ((3S,5S)-5-methyl-4-tosylmorpholin-3-yl)methanol 13a.

Fig. S-45: DEPT Spectra of ((3S,5S)-5-methyl-4-tosylmorpholin-3-yl)methanol 13a.

Fig. S-46: COSY Spectra of ((3S,5S)-5-methyl-4-tosylmorpholin-3-yl)methanol 13a.

Fig. S-47: NOESY Spectra of ((3S,5S)-5-methyl-4-tosylmorpholin-3-yl)methanol 13a.

Fig. S-48: HPLC Spectra of ((3S,5S)-5-methyl-4-tosylmorpholin-3-yl)methanol 13a.

Fig S 49: 1H Spectra of ((3S 5S) 5 (4 Metho ben l) 4 tos lmorpholin 3 l)methanol 13bFig. S-49: 1H Spectra of ((3S,5S)-5-(4-Methoxybenzyl)-4-tosylmorpholin-3-yl)methanol 13b.

Fig. S-50: 13C Spectra of ((3S,5S)-5-(4-Methoxybenzyl)-4-tosylmorpholin-3-yl)methanol 13b.

Fig. S-51: HPLC Spectrum of ((3S,5S)-5-(4-Methoxybenzyl)-4-tosylmorpholin-3-yl)methanol 13b.

Fig S-52: 1H Spectra of (3S 6R)-3-(4-Methoxybenzyl)-4-tosyl-1 4-oxazepan-6-ol 14eFig. S-52: H Spectra of (3S,6R)-3-(4-Methoxybenzyl)-4-tosyl-1,4-oxazepan-6-ol 14e.

Fig. S-53: 13C Spectra of ((3S,6R)-3-(4-Methoxybenzyl)-4-tosyl-1,4-oxazepan-6-ol 14e.

Fig. S-54: HPLC Spectra of (3S,6R)-3-(4-Methoxybenzyl)-4-tosyl-1,4-oxazepan-6-ol 14e. 3


Fig. S-55 : 1H spectra of (3S,6S)-3-iso-Propyl-1,4-oxazepan-6-ol 15.

Fig. S-56: 13C spectra of (3S,6S)-3-iso-Propyl-1,4-oxazepan-6-ol 15.

Fig. S-57: 1H spectra of (3S,5S)-3-((tert-butyldimethylsilyloxy)methyl)-5-isopropyl-4-tosylmorpholine 16.

4


NTs4

Figure S‐1: 1H spectrum (200 MHz, CDCl3) of 4. 5


NTs4

Figure S‐2:13C spectrum (75 MHz, CDCl3) of 4. 6


NTs12a

7Figure S‐3: 1H spectrum (300 MHz, CDCl3) of 12a.


NTs12a

8Figure S‐4:13C spectrum (75 MHz, CDCl3) of 12a.


NTs NH

12c

Figure S-5: 1H spectrum (300 MHz, CDCl3) of 12c. 9


NTs NH

12c

Figure S-6: 13C spectrum (75MHz, CDCl3) 12c.10


NTs

CH3

12d

Figure S-7: 1H spectrum (300 MHz, CDCl3) of 12d.11


NTs

CH3

12d

Figure S-8: 13C spectrum (75MHz, CDCl3) 12d. 12


TsN

TsN

OHO7

O

NHO

6

+

Figure S‐9: 1H spectrum (300 MHz, CDCl3) of inseparable 6 + 7 (2.1:1). 13


O

TsN

HOO

TsN

HO+

OHO7

O6

Figure S‐10: 13C spectrum (75MHz, CDCl3) of mixture compounds. 14


O

TsN

TBDMSO9

O

TsN

TBDMSO

8

+

98

Figure S‐11: 1H spectrum (300 MHz, CDCl3) of 8 + 9 (3.8:1). Reaction is performed at rt. 15


O

TsN

TBDMSO9

O

TsN

TBDMSO

8

+

98

Figure S‐12: 13C spectrum (75 MHz, CDCl3)of 8 & 9. 16


TsN

TBDMSO

O8

TBDMSO

CDCl3CDCl3

Expanded aromatic region

Figure S‐13: Pure 1H spectrum (300 MHz, CDCl3) of 8. When reaction is carried out at 0 oC.17


Ts

O

sN

7HO

Figure S‐14: 1H spectrum (300 MHz, CDCl3 ) of 7. 18


O

TsN

HO7

Figure S‐15:13C spectrum (50 MHz, CDCl3) of 7. 19


TsN

O

7HO

Figure S‐16: HPLC spectrum of 7.20


O

TsN

HO

6

CDCl3



O

TsN

HO

6

Figure S‐18:13C spectrum (50 MHz, CDCl3) of 6.22


O

TsN

MsO

10

Figure S‐19: 1H spectrum (300 MHz, CDCl3) of 10.23


O

TsN

MsO

10



O

TsN

MsO

10

Figure S‐21: HPLC spectrum of 10 25


Ts

O

TsN

14a

HO

Figure S‐22: 1H spectrum (200 MHz, CDCl3) 14a. 26


Ts

O

TsN

14a

HO

Figure S‐23: 13C spectrum (50 MHz, CDCl3) 14a. 27


O

TsN

HO O

14a

HO

Figure S‐24: HPLC spectrum of 14a. 28


O

TsN

HO14b

Figure S‐25: 1H spectrum (300 MHz, CDCl3) 14b. 29


O

TsN

14bHO

14b

Figure S‐26: 13C spectrum (75 MHz, CDCl3) 14b. 30


TsN

O

14bHO

Figure S‐27: HPLC spectrum of 14b. 31


O

TsN NH

HO O

14cHO

32Figure S‐28: 1H spectrum (200 MHz, CDCl3) 14c.


O

TsN NH

HO O

14cHO

33Figure S‐29: 13C spectrum (75 MHz, CDCl3) 14c.


TsN

O

N

14c

NH

HO

34Figure S‐30: HPLC spectrum of 14c.


O

TsN

TBDMSO

Figure S‐31: 1H spectrum (300 MHz, CDCl3) of (3S,5S)‐3‐((tert‐butyldimethyl silyloxy) methyl)‐5‐methyl‐4‐tosylmorpholine . 35


O

TsN

TBDMSO

Figure S‐32: 13C spectrum (50 MHz, CDCl3) of (3S,5S)-3-((tert-butyldimethyl silyloxy) methyl)-5-methyl-4-tosylmorpholine.

36


O

TsN

14dHO

14d

Figure S‐33: 1H spectrum (300 MHz, CDCl3) 14d. 37


O

TsN

14dHO

14d

Figure S‐34: Expanded aliphatic region of 14d.38


O

TsN

14dHO

14d

Figure S‐35: 13C spectrum (50 MHz, CDCl3) 14d.39


O

TsN

14dHO

14d

Figure S‐36: DEPT spectrum (75 MHz, CDCl3) of 14d. 40


O

TsN

CH3H

HH1

235

6(δ 3 )

(δ 3.71)

(δ 4.14)

HO

HH

(δ 3.89)

(δ 3.72)

7

Jcis = 4.2 Hz

Jcis = 4.3 Hz

CH3-3

Hβ-5

Hα-5

O

14d

H

H H

16

J trans = 8.7 Hz

(δ 3.55)

(δ 3.81)(δ 3.08)

HOH(δ 4.09) 7

OH-6Hβ-7Hα-2

Hβ-2

Hα-7

CH-6CH-3

Figure S‐37: COSY spectrum of 14d (300 MHz, CDCl3). 41


TsN

CH3H

HH1

235

6

(δ 3.71)

(δ 4.14)

HO

HH

(δ 3.89)

(δ 3.72)

7

Jcis = 4.2 Hz

Jcis = 4.3 Hz

O

14d

H

H H

16

J trans = 8.7 Hz

(δ 3.55)

(δ 3.81)(δ 3.08)

HOH(δ 4.09) 7

Figure S‐38: Expanded COSY spectrum of 14d. 42


TsN

CH3H

H

O

N

14d

HH

H H

12

356

H

HHO 7

41Figure S‐39: NOESY spectrum (400 MHz, CDCl3) of 14d. 43


TsN

CH3H

H

O

14d

HH

H H

12

356

H

HHO 7

Figure S‐40: Expanded NOESY spectrum of 14d. 44


O

TsN

HO O

TsN

HO+

14d 13a

Figure S‐41: HPLC spectrum for mixture of 14d + 13a.

45


O

TsN

HO14d

HO

Figure S‐42: HPLC spectrum of pure 14d. 46


O

TsN

HO

13a

47Figure S‐43: 1H spectrum (300 MHz, CDCl3) 13a.


O

TsN

HO

13a

48Figure S‐44: 13C spectrum (50 MHz, CDCl3) 13a.


TsN

O

NHO

13a

Figure S‐45: DEPT spectrum (50 MHz, CDCl3) of 13a. 49


TsN

HO

O13a

Figure S‐46: COSY spectrum of 13a (300 MHz, CDCl3).50


O

TsN

HO

13a

HH

Figure S‐47: NOESY spectrum of 13a (300 MHz, CDCl3). 51


TsN

HO

O13a

52Figure S‐48: HPLC spectrum of 13a.


O

TsN

HO

OMe13b13b

FigureS‐49: 1H spectrum (300 MHz, CDCl3) of 13b.53


O

TsN

HO

OMe13b13b

FigureS‐50: 13C spectrum (50 MHz, CDCl3) 13b. 54


O

TsN

HO

OMeO OMe13b

55Figure S‐51: HPLC Spectrum of 13b


O

TsN OMe

14eHO

14e

Figure S‐52: 1H spectrum (300 MHz, CDCl3) of 14e. 56


O

TsN OMe

14eHO

14e

Figure S‐53: 13C spectrum (50 MHz, CDCl3) 14e. 57


Ts

O

N OMe

14eHO

Figure S‐54: HPLC spectrum of 14e. 58


HN 3S

O6S15

HO



O

HN 3S

6S15

HO

15

Figure S‐56: 13C spectrum (75 MHz, CDCl3) 15. 60


O

HN

TBDMSO

16

Figure S‐57: 1H spectrum (75 MHz, CDCl3) 16. 61


Supporting Information OOene Pot SySy es snthesis ofAmino ... · Ring Opening Sequences†...

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