A facile enantioselective synthesis of (S)-N-(5-chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol via proline-catalyzed asymmetric alpha-aminooxylation and alpha-amination of aldehyde

作者：Rawat Varun; Chouthaiwale Pandurang V; Chavan Vilas B; Suryavanshi Gurunath; Su***** Arumugam^*

来源：Tetrahedron Letters, 2010, 51(50): 6565-6567.

DOI：10.1016/j.tetlet.2010.10.029

• Alzheimer's disease
• alpha-Amination
• Amino alcohol
• alpha-Aminooxylation
• Proline

A high-yielding enantioselective synthesis of the bioactive (S)-N-(5-chlorothiophene-2-sulfonyl)beta,beta-diethylalaninol (1), a Notch-1-sparing gamma-secretase inhibitor metabolite (with EC50 = 28 nM) effective in reduction of All production in vivo, has been realized starting from readily available 3-pentanone. The key steps of the synthesis are proline-catalyzed alpha-aminooxylation and alpha-amination of aldehyde: the latter contributing an overall yield of 45.2% and 98% ee.

• 出版日期2010-12-15