Book Review, Stereodirected Synthesis with Organoboranes

Abstract

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. We have found a mild, efficient route from asymmetric boronic esters via alkyltrifluoroborates to reactive alkyldi-fluoroborane intermediates, which are converted to asym-metric secondary amines via reaction with organic azides. Vedejs and co-workers reported that arylboronic acids react with potassium bifluoride to form aryltrifluoroborates, which are converted to aryldifluoroborane intermediates by trim-ethylsilyl chloride. 1,2 Organotrifluoroborates prepared by the Vedejs route have been found useful by others, 3 but organodifluoroboranes remain relatively unexplored. 4 Our method of asymmetric synthesis based on R-halo boronic ester chemistry provides a wide variety of function-alized boronic ester intermediates in very high enantiomeric and diastereomeric purity, 5 but the scope of displacements of boron from carbon has been limited by the low reactivity of boronic esters. Thermodynamics disfavors hydrolysis of the pinanediol or 1,2-dicyclohexylethanediol (DICHED) esters used in our synthetic method. Separation of the diol group from boron requires an exothermic reaction 6 or separation of the diol and the organoboron units into separate phases, 7 which is not always practical. Glass-catalyzed reaction of boronic esters with thionyl chloride and imidazole has provided good recovery of the chiral diols, but efficient hydrolysis of the chloroborane imidazole derivatives has proved elusive. 8 The direct reaction of pinanediol or DICHED boronic esters with potassium bifluoride under the Vedejs conditions (1) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf, M. R. J. Org. Chem. 1995, 60, 3020-3027. (2) It has been reported that the ethanolamine ester of diphenylborinic acid was converted to potassium (difluoro)(diphenyl)borinate by KHF2: Thierig, D.; Umland, F. Naturwissenschaften 1967, 54, 563. Vedejs et al. speculated that boronic esters might also react but did not test the possibility. (3) (a) Batey, R. A.; Thadani, A. N.; Smil, D. V. Org. Lett. 1999, 1, 1683-1686. (b) Molander, G. A.; Ito, T. Org. Lett. 2001, 3, 393-396. (4) (a) Classical synthesis: McCusker, P. A.; Glunz, L. J. J. Am. Chem. Soc. 1955, 77, 4253-4255. McCusker, P. A.; Makowski, H. S. J. Am. Chem. Soc. 1957, 79, 5185-5188. (b) From R-amido boronic acids and aqueous hydrofluoric acid: Kinder, D. H.; Katzenellenbogen, J. A. J. Med. Chem. 1985, 28, 1917-1925. (c) R-Amido group makes boron tetracoordinate in boronic ester analogue: Matteson, D. S.; Michnick, T. J.; Willett, R. D.; Patterson, C. D.