Optimized Catalytic Enantioselective Aryl Transfer Process Gives Access to mGlu2 Receptor Potentiators

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• 作者：Nicholas A. Magnus ; Peter B. Anzeveno ; D. Scott Coffey ; David A. Hay ; Michael E. Laurila ; Jeffrey M. Schkeryantz ; Bruce W. Shaw ; Michael A. Staszak
• 刊名：Organic Process Research & Development
• 出版年：2007
• 出版时间：May 2007
• 年：2007
• 卷：11
• 期：3
• 页码：560 - 567
• 全文大小：351K
• 年卷期：v.11,no.3(May 2007)
• ISSN：1520-586X

文摘

An asymmetric enantioselective aryl transfer reaction wasdeveloped to give access to the diarylmethanol 7 and ultimatelyacetate 2 which is useful for the preparation of mGlu2 receptorpotentiators (Scheme 3). The aryl transfer chemistry involvedthe preparation of a proposed arylalkylzinc species 14 fromboroxine 16 and diethylzinc (DEZ), and reacting this mixturewith aldehyde 5 in the presence of chiral ligand 15. During thecourse of optimizing the preparations of proposed intermediate14 and diarylmethanol 7, an understanding of optimal stoichiometry and reaction times was gained through empiricalobservation, the use of solution IR, and analyzing off-gases viareal time gas analysis/mass spectroscopy. The preparation ofdiarylmethanol 7 and subsequent conversion into acetate 2required carefully selected workups, selective extractions, andazeotropic distillations to generate a series of stock solutionsto accommodate oil intermediates that finally gave acetate 2 asa crystalline solid with >99% ee.