Highly Stereoselective Prins Cyclization of (Z)- and (E)-- - - PowerPoint PPT Presentation

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Highly Stereoselective Prins Cyclization of (Z)- and (E)-- - - PowerPoint PPT Presentation

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Highly Stereoselective Prins Cyclization of (Z)- and (E)-- Brominated Homoallylic Alcohols to 2,4,5,6-Tetrasubstituted Tetrahydropyrans Feng Liu and Teck-Peng Loh, Organic Letters, 2007, 9(11) 2063-2066 Br Br Br Br R 1 O R 2 R 1 O R 2

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SLIDE 1

Highly Stereoselective Prins Cyclization of (Z)- and (E)-- Brominated Homoallylic Alcohols to 2,4,5,6-Tetrasubstituted Tetrahydropyrans

Feng Liu and Teck-Peng Loh, Organic Letters, 2007, 9(11) 2063-2066 O O R1 R1 Br Br R2 Br R2 Br

Korede Agusto @ Wipf Group 1 10/29/2007

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SLIDE 2

Tetrahydropyrans in Nature

diospongin B

O OH Ph Ph O

O HO O O OH

kendomycin

Korede Agusto @ Wipf Group 2 10/29/2007

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SLIDE 3

Korede Agusto @ Wipf Group 3 10/29/2007

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SLIDE 4

Korede Agusto @ Wipf Group 4 10/29/2007

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SLIDE 5

Previous Approaches to THP’s

Korede Agusto @ Wipf Group 5 10/29/2007

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SLIDE 6

O CO2Et Br Br

Bu3SnH, AIBN, Benzene reflux 81%

O O Br Br CO2Et CO2Et

Radical Cyclization (Towards Dactomylenes): JACS, 1995, 117, 8017-8018 Hetero-Diels-Alder Reaction (Towards Ambruticin):

TBSO OBn H O OTBDPS

+ cat. 64%, 94%ee

OTBS OBn TBDPSO

JACS, 2001, 123, 10772-10773

Korede Agusto @ Wipf Group 6 10/29/2007

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SLIDE 7

The Prins Cyclization Approach

Innovative Features:

  • Highly convergent
  • Versatile intermediate for further functionalization
  • Moderate to high yields and excellent stereo control
  • First stereoselective dibromo-THP via Prins cyclization

O R1 Br R2

Br

O R1 Br Br R2

OH R1 Br O R2 H

InBr3 , TMSBr CH2Cl2 , 0oC, 90 min

OH R1 CH3 O O R1 R1 Br Br R2 Br R2 Br

  • r
  • r

Korede Agusto @ Wipf Group 7 10/29/2007

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SLIDE 8

Scope of Reaction

Korede Agusto @ Wipf Group 8 10/29/2007

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SLIDE 9

Further Work

conditions

O R1 R2 O R1 R2 Br O O R1 R1 Br Br R2 Br R2 Br

  • r

conditions

O R1 R2

O OH

Further Work:

  • Application of methodology to natural products
  • Improvement of scope of possibilities for R1 and R2

Korede Agusto @ Wipf Group 9 10/29/2007

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SLIDE 10

Conclusions

  • Development of efficient use of Prins Cyclization to

afford 2,6-cis-4,5-dibromo-tetrasubstituted THP’s

  • Effective stereocontrol
  • Development of dibromo-THP’s that are versatile

for further functionalization.

Korede Agusto @ Wipf Group 10 10/29/2007