Asymmetric Alkyldifluoroboranes and Their Use in Secondary Amine Synthesis

Abstract

[reaction: see text] Asymmetric diol boronic esters with potassium bifluoride form the corresponding alkyltrifluoroborate and free diol under mild conditions. Defluoridation with tetrachlorosilane produces an alkyldifluoroborane intermediate. This conversion of relatively unreactive boronic esters to derivatives that are strong Lewis acids opens new synthetic opportunities, as illustrated by the preparation of (R)-2-phenylpyrrolidine in 98% ee from a pinanediol or 1,2-dicyclohexyl-1,2-ethanediol boronic ester via potassium (2-phenyl-4-azidobutyl)trifluoroborate.

New Asymmetric Syntheses with Boronic Esters and Fluoroboranes

“…This reaction has proved equally applicable to alkyltrifluoroborate salts (15) [11]. However, we have found that silicon tetrachloride reacts faster and achieves rapid conversion to the alkyldifluoroboranes at room temperature.…”

“…The next obvious step was to attempt the direct cleavage of a DICHED boronic ester (7) as outlined in Scheme 4, and somewhat to our surprise, the reaction proved rapid and efficient at room temperature, directly yielding free DICHED (10) and potassium alkyltrifluoroborate (15) [11].…”

“…The reaction was shown to be reversible by mixing the phenyltrifluoroborate salt (15, R 1 = Ph) with pinanediol (16) under conditions similar to those used for the usual reactions and showing that ~30 % was converted to the pinanediol borate (12) [11].…”

“…Reactions were generally run 0.5-2 h at ~22 °C. For isolation, the methanol was removed under vacuum and the residue was treated with acetonitrile to dissolve the alkyltrifluoroborates (15), DICHED (10), and any unchanged boronic ester 7, leaving the excess unchanged potassium bifluoride (12) were not so thoroughly tested, but with R 1 = Ph or (R)-4-azido-1-phenylbutyl, conversions were ~70 % [11]. The efficient recovery of the valuable chiral diol is a significant advantage of the potassium bifluoride reaction.…”

“…Formation of amide derivatives with Mosher's acid chloride [(R)-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride] followed by GC/MS analysis indicated enantiomeric purities of 98 ± 0.4 % for samples of 2-phenylpyrrolidine derived from either the DICHED boronic ester or the pinanediol boronic ester [11].…”