Practical asymmetric conjugate alkynylation of meldrum's acid-derived acceptors: Access to chiral β-alkynyl acids

Journal of the American Chemical Society

Volumn 132, Issue 2, 2010, Pages 436-437

  Cui, Sheng ^a   Walker, Shawn D ^a   Woo, Jacqueline C S ^a   Borths, Christopher J ^a   Mukherjee, Herschel ^a   Chen, Maosheng J ^a   Faul, Margaret M ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYNYLATIONS; ALKYNYLS; CHEMICAL EQUATIONS; ENANTIOSELECTIVE CONJUGATE ADDITION; MELDRUM'S ACIDS; SYNTHETIC CHEMISTRY;

CHEMICAL REACTIONS;

ACIDS;

ALKYNYL GROUP;

ALKYNYLATION; ARTICLE; CHIRALITY; CONJUGATION; CRYSTALLIZATION; ENANTIOSELECTIVITY; TEMPERATURE;

ALKYNES; CARBOXYLIC ACIDS; DIOXANES; MOLECULAR STRUCTURE; STEREOISOMERISM;

EID: 74949097468     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja909105s     Document Type: Article

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24. A variety of other chiral ligands and metals, including copper, rhodium, and lithium, were also evaluated, but they afforded lower yields and enantioselectivities.
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31. Ultimately, trifluoroethanol was selected for further optimization studies because of its low cost and easy removal by distillation.
32. No reaction was detected below-30°C, and reactions at 0 and 30°C gave 92 and 88% ee, respectively.
33. 2OH) at rt for 24 h, 93% conversion and 94% ee was observed.
34. (b) Other evaluated solvents (Me-THF, MTBE, DME, toluene) provided lower ee (<80%) and yield (<90%).
35. 2Zn were equally efficient.
36. (d) The enantioselectivity was not dependent on the concentration (0.04-0.2 M).
37. (e) The order of addition of reagents during the zincate preparation had no effect.
38. In Scheme 1, zincate 4 is depicted as a monomer for clarity. Preliminary NMR studies indicate that several different zincate species exist in solution.