D.A. Evans Diastereoselective Enantioselective Carbonyl Addition Chem 206 ■ Problems http://www.courses.fasharvardedul-chem206/ Propose a mechanism for tihs highly diastereoselective transformation, Evans, Hoveyda JACS112,6447(1990) Chemistry 206 Advanced Organic Chemistry diastereoselection 15%Sm >100 Lecture number 21 Cume Question, 2000: Chiral amino alcohol 1 efficiently mediates the addition of Enantioselective Carbonyl Addition diethylzinc to aromatic aldehydes. While a number of other amino alcohols are also effective in controlling the absolute of the addition process, this amino alcohol has been the focus of a recent computational investigation that addresses the preferred Enantioselective addition of R2 Zn to aldehydes transition state geometry for this addition process(Pericas, et al. J. Org. Chem. 2000, 65, 7303 and references cited therein). It should be noted that, while 1 is not the actual catalyst, it is Enantioselective Reduction of ketones imines modified under the reaction conditions to the competent catalytic agent. Provide a detailed mechanism for the overall transformation. Use 3-dimensional representations to illustrate Reading Assignment for this Week the absolute stereochemical aspects of the indicated transformation. Carey& Sundberg: Part A; Chapter 8 Reactions of Carbonyl Compounds Carey& Sundberg: Part B: Chapter 2 toluen Reactions of Carbon Nucleophiles with Carbonyl Compounds Carey& Sundberg: Part B; Chapter 5 Cume Question, 2000. Corey's introduction of chiral ox Reduction of Carbonyl& Other Functional Groups borane-mediated enantioselective reduction of ketones re netric synthesis(Corey Helal, Angew. Chem. Int. m detailed mechanism for the overall transformation. Use 3-dimensional representations to Carbonyl Addn: Felkin Control: Evans, JACS 1996, 118, 4322(handout) illustrate the absolute stereochemical aspects of the indicated transformation. Carbonyl Additon: Chelate Control: Evans JACS 2001, ASAP(handout) Enantioselective Carbonyl Reduction: Corey Angew. Chem. Int Ed 1998,371986-2012 handout) Enantioselective Carbonyl Addition(R2Zn): Noyori Angew. Chem 0.1 equiv 1 Int Ed. 1991, 30, 49-69(handout) e 97%ee 1 equiv BH3THF 1,(R Wednesda Matthew d shair November 6. 2002http://www.courses.fas.harvard.edu/~chem206/ R1 Me Me OH O R2CHO H O Ph OH N Ph Ph N B O Ph Ph R H Me O (R) Et2Zn, 0 °C toluene 1 equiv BH3•THF R1 Me Me R2 O OH O Me OH Et OH (R) (S) D. A. Evans Chem 206 Matthew D. Shair Wednesday, November 6, 2002 ■ Reading Assignment for this Week: Carey & Sundberg: Part A; Chapter 8 Reactions of Carbonyl Compounds Diastereoselective & Enantioselective Carbonyl Addition Chemistry 206 Advanced Organic Chemistry Lecture Number 21 Enantioselective Carbonyl Addition ■ Enantioselective addition of R2Zn to aldehydes ■ Enantioselective Reduction of Ketones & Imines Carey & Sundberg: Part B; Chapter 2 Reactions of Carbon Nucleophiles with Carbonyl Compounds Carey & Sundberg: Part B; Chapter 5 Reduction of Carbonyl & Other Functional Groups Carbonyl Addn: Felkin Control: Evans, JACS 1996, 118, 4322 (handout) Carbonyl Additon: Chelate Control: Evans JACS 2001, ASAP (handout) Enantioselective Carbonyl Reduction: Corey Angew. Chem. Int Ed. 1998, 37, 1986-2012 (handout) Enantioselective Carbonyl Addition (R2Zn): Noyori Angew. Chem. Int Ed. 1991, 30, 49-69 (handout) ■ Problems: 15% SmX3 catalyst diastereoselection > 100:1 Propose a mechanism for tihs highly diastereoselective transformation, Evans, Hoveyda JACS 112, 6447 (1990) Cume Question, 2000: Chiral amino alcohol 1 efficiently mediates the addition of diethylzinc to aromatic aldehydes. While a number of other amino alcohols are also effective in controlling the absolute course of the addition process, this amino alcohol has been the focus of a recent computational investigation that addresses the preferred transition state geometry for this addition process (Pericas, et al. J. Org. Chem. 2000, 65, 7303 and references cited therein). It should be noted that, while 1 is not the actual catalyst, it is modified under the reaction conditions to the competent catalytic agent. Provide a detailed mechanism for the overall transformation. Use 3-dimensional representations to illustrate the absolute stereochemical aspects of the indicated transformation. 1 0.06 equiv 1 97% ee 1, (R = H or Me) 0.1 equiv 1 Cume Question, 2000: Corey's introduction of chiral oxazaborolidine catalysts 1 in the borane-mediated enantioselective reduction of ketones represents an important advance in asymmetric synthesis (Corey & Helal, Angew. Chem. Int. Ed. 1998, 37, 1986-2012). Provide a detailed mechanism for the overall transformation. Use 3-dimensional representations to illustrate the absolute stereochemical aspects of the indicated transformation. 97% ee