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

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 Korede Agusto @ Wipf Group 1 10/29/2007

Tetrahydropyrans in Nature OH O OH O Ph O Ph O HO diospongin B O kendomycin Korede Agusto @ Wipf Group 2 10/29/2007

Korede Agusto @ Wipf Group 3 10/29/2007

Korede Agusto @ Wipf Group 4 10/29/2007

Previous Approaches to THP’s Korede Agusto @ Wipf Group 5 10/29/2007

Radical Cyclization (Towards Dactomylenes): O Bu 3 SnH, AIBN, Benzene O O CO 2 Et CO 2 Et reflux CO 2 Et Br 81% Br Br Br JACS, 1995 , 117 , 8017-8018 Hetero-Diels-Alder Reaction (Towards Ambruticin): OTBS TBSO O cat. + OBn TBDPSO H OTBDPS 64%, 94%ee JACS, 2001 , 123 , 10772-10773 OBn Korede Agusto @ Wipf Group 6 10/29/2007

The Prins Cyclization Approach Br Br OH R 1 O R 1 O R 2 Br or R 2 H InBr 3 , TMSBr or OH Br CH 2 Cl 2 , 0 o C, 90 min CH 3 Br R 1 R 1 O R 2 Br Br Br Br R 1 R 1 O R 2 R 2 O Innovative Features: •Highly convergent •Versatile intermediate for further functionalization •Moderate to high yields and excellent stereo control •First stereoselective dibromo-THP via Prins cyclization Korede Agusto @ Wipf Group 7 10/29/2007

Scope of Reaction Korede Agusto @ Wipf Group 8 10/29/2007

Further Work Br Br Br R 1 O R 2 R 1 O R 2 conditions conditions or R 1 O R 2 O Br Br OH R 1 O R 2 R 1 O R 2 Further Work: •Application of methodology to natural products •Improvement of scope of possibilities for R 1 and R 2 Korede Agusto @ Wipf Group 9 10/29/2007

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