D.A. Evans Cycloaddition Reactions-4 Chem 206 Transformations of B-Lactones The Staudinger Reaction In this process, the ilustrated ketene, generated in situ from an acid chloride, △orBF3 stereoselective process. When the azo-methine(RN=CHR) geomety n theo undergoes reaction with the indicated substrates to form B -lactams in reactant is(z) the product stereochemistry is trans(eq 1). In fashion, the(E) imine affords the cis-substituted product (eq 2). While RLi(2eq) O2H Arnold. L D: Drover. j. C j : Vedras J C. J. Am Chem.Soc.1987.107.4649 a The stepwise mechanism or acid Nu= OH2, ROH, R2NH Application in Natural Product Synthesis: Ginkolide B Ther are two contortaory modes. Meo J. Corey JACS 1988, 110, 649 If you control the conrotatory mod you control the absolute stereochemistry of the reaction ①“的 CMes Et3N 2.NBu3, toluene,△ D2H Evans, SogrenTet. Lett. 1985, 26, 3783, 3787 diastereoselection >95: 5 ns, Tet. Lett:1988,29,5065 Joc1982,47,3470. ition/fragmentation strategies for the synthesis of natural and unnatural products. Winkler, J D; Bowen, C ta,F.chem.Re1995,95,203 eoselective intermolecular[2+2H-photocycloaddition reactions and their application in synthesis T. Synthesis 1998, 68O MeO CMe3 CO2H O R 2 R 1 O O R2N O O O O R 2 R 1 O Me2S CH2COCl H NEt3 S O O O R 1 Nu OH R 2 O R 2 R 1 R2N CO2H R' O CMe3 H O H O R Cl C O R H O Cl N O Ph O Et3N N S H N Bn H Ar C O R H Et3N N S H N R H R N S H R –O H N S H R –O H N Bn Ar O H H N O Ph O N S O H H R N R R O H H R N S O H H R N S O H H R N Bn Ar O H H N O Ph O D. A. Evans Cycloaddition Reactions-4 Chem 206 The Staudinger Reaction In this process, the illustrated ketene, generated in situ from an acid chloride, undergoes reaction with the indicated substrates to form b -lactams in a stereoselective process. When the azo-methine (RN=CHR) geometry in the reactant is (Z) the product stereochemistry is trans (eq 1). In a complementary fashion, the (E) imine affords the cis-substituted product (eq 2). While this transformatlion could be viewed as a [2s+2a] cycloaddition, it is felt that this reaction is stepwise. (1) (2) ■ The stepwise mechanism + (1) conrotatory closure + conrotatory closure enantiomers Ther are two contortaory modes. If you control the conrotatory mode, you control the absolute stereochemistry of the reaction: See also Evans, Williams, Tet. Lett. 1988, 29, 5065. Evans, SjogrenTet. Lett. 1985, 26, 3783, 3787. diastereoselection > 95:5 80-90% yields "[2+2] photocycloaddition/fragmentation strategies for the synthesis of natural and unnatural products.", Winkler, J. D.; Bowen, C. M.; Liotta, F. Chem. Rev. 1995, 95, 2003. "Stereoselective intermolecular [2+2]-photocycloaddition reactions and their application in synthesis.", Bach, T. Synthesis 1998, 683. Transformations of -Lactones _ + D or BF3 -CO2 base or acid Nu = OH2, ROH, R2NH CuCN R'Li (2eq) Arnold, L. D.; Drover, J. C. J.; Vederas, J. C. J. Am. Chem. Soc. 1987, 107, 4649. Application in Natural Product Synthesis: Ginkolide B, E. J. CoreyJACS 1988, 110, 649. 1. (COCl)2 , PhH, D 2. NBu3 , toluene, D JOC 1982, 47, 3470