A Study on the Diastereoselective Synthesis of alpha-Fluorinated beta 3-Amino Acids by alpha-Fluorination

作者：Peddie Victoria; Abell Andrew D^*

来源：Helvetica Chimica Acta, 2012, 95(12): 2460-2473.

DOI：10.1002/hlca.201200520

• Amino acids
• Fluorine compounds
• Stereoselective synthesis

The treatment of a beta 3-amino acid methyl ester with 2.2 equiv. of lithium diisopropylamide (LDA), followed by reaction with 5 equiv. of N-fluorobenzenesulfonimide (NFSI) at -78 degrees for 2.5 h and then 2 h at 0 degrees, gives syn-fluorination with high diastereoisomeric excess (de). The de and yield in these reactions are somewhat influenced by both the size of the amino acid side chain and the nature of the amine protecting group. In particular, fluorination of N-Boc-protected beta 3-homophenylalanine, beta 3-homoleucine, beta 3-homovaline, and beta 3-homoalanine methyl esters, 5 and 911, respectively, all proceeded with high de (%26gt;86% of the syn-isomer). However, fluorination of N-Boc-protected beta 3-homophenylglycine methyl ester (16) occurred with a significantly reduced de. The use of a Cbz or Bz amine-protecting group (see 3 and 15) did not improve the de of fluorination. However, an N-Ac protecting group (see 17) gave a reduced de of 26%. Thus, a large N-protecting group should be employed in order to maximize selectivity for the syn-isomer in these fluorination reactions.

• 出版日期2012-12