Reduction organic reaction 11还原有机反应.pdfVIP

Chapter 9 Remote Acyclic Diastereocontrol in Hydride Reductions of 1,n-Hydroxy Ketones Bruce E. Maryanoff, Han-Cheng Zhang, Michael J . Costanzo, Bruce D. Harris, and Cynthia A. Maryanoff g r R. W. Johnson Pharmaceutical Research Institute, o . s Spring House, PA 19477 c a . s b u p 9 / 0 / : 0 p h t c t h 1. | 4 9 6 0 0- We have discovered asymmetric reductions in hydroxy ketone systems 0 2 6 9 2, 9 (see I) with high diastereoselectivity between remote (e.g., 1,5 and 1,6) 2 1- carbon stereocenters. The favorable results are presumably achieved r k e b b / through the formation of bicyclic metal chelates that involve the intra- o 1 t 2 c 0 chain nitrogen atom. For example, reduction of I (R = Ph, m = n = 1) O 1 . n 0 with R-Alpine-Hydride or Zn(BH )2 in CH2Cl2 gave high anti stereo­ o 1 4 : H i selectivity (II:IIΙ = anti:syn = 10:1 or 13:1, respectively). Reduction of C o d E | I (R = Ph, m = 1, n = 2) with R-Alpine-Hydride in CH Cl afforded a 2 2 T 6 9 preponderance of anti diastereomer (II:IIΙ = anti:syn = 12:1). Evidence 9 I 1 is presented to support a chelation-controlled mechanism involving a C , S 3 1 bicyclic metal complex. Our studies with a range of substrates a