First application of tunable alkyl or aryl sulfinamides to the stereoselective synthesis of a chiral amine: Asymmetric synthesis of (R)-didesmethylsibutramine ((R)-DDMS) using (R)triethylmethylsulfinamide ((R)-TESA)

Organic Letters

Volumn 4, Issue 23, 2002, Pages 4025-4028

  Han, Zhengxu ^a   Krishnamurthy, Dhileepkumar ^a   Pflum, Derek ^a   Grover, Paul ^a   Wald, Stephen A ^a   Senanayake, Chris H ^a  

^a SUNOVION PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CAMINOSIDE A; CYCLOBUTANE DERIVATIVE; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; GLYCOLIPID; SIBUTRAMINE;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; ISOLATION AND PURIFICATION; STEREOISOMERISM; SYNTHESIS;

CYCLOBUTANES; GLYCOLIPIDS; INDICATORS AND REAGENTS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; STEREOISOMERISM;

EID: 0037078849     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol026699q     Document Type: Article

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30. (b) All new sulfinyl aldimine gave satisfactory analytical data.
31. 2 minimizes the formation of byproducts.
32. 7n
33. For a similar methyl transfer process in ketimine see ref 7f.
34. Isolation of DDMS as the DDMS-D-TA salt may not be effective in the presence of TMEDA. Therefore the use of TMEDA was not considered for further optimization.
35. Use of 1:1 THF:toluene as solvent has the same effect of temperature on % ee as THF alone.
36. In the production environment 9c is preferred over 9a due to low volatility of byproducts from hydrolysis reaction.
37. Red-Al is less expensive and more efficient in the large-scale reduction of 4a to 4b.