Asymmetric synthesis with boronic esters

Abstract

Reaction of (dichloromethyl)lithium with (+)-pinanediol alkylboronates at -100 °C followed by treatment with anhydrous zinc chloride and warming to 0-25 °C results in insertion of a chloromethyl group into the carbon-boron bond to increase the chain length by one carbon and form (IS)-1-chloroalkylboronic esters in 85–99% yields and usually 99% or better diastereoselectivities. With (+)-pinanediol methylboronate the diastereoselectivity falls to 95%. The chloride can be replaced by Grignard reagents to form sec-alkylboronic esters, or by lithium benzyloxide to form 1-benzyloxyboronic esters. A second chiral center can be introduced by another reaction with (dichloromethyl)lithium, and in principle there is no limit to the number of adjacent chiral centers that could be assembled in this manner. The process tolerates other functional groups as long as they are inert toward carbanions. It is possible to use (-)-pinanediol to obtain the corresponding (lR)-l-chloroboronic esters. The utility of this approach to chiral synthesis has been demonstrated with simple insect pheromones containing two chiral centers. Another useful chiral directing group is (R,R)-2,3-butanediol, which yields 95–96% diastereoselectivities, even in the formation of the 1-chloroethylboronic ester. An advantage of this directing group is that it yields the same results via reaction of (R,R)-2,3-butanediol dichloromethylboronate with Grignard or lithium reagents, because the C2 symmetry of the chiral group leads to the same borate complex intermediate regardless of the order of attachment of the dichloromethyl and alkyl groups. A second advantage is that the butanediol 1-chloroalkylboronic esters hydrolyze readily on contact with water, and the resulting (IS)-1-chloroalkylboronic acids are usually crystalline solids which can be enantiomerically purified by recrystallization, and which could easily be esterified with a chiral group which directs the next 1-chloroboronic ester to be the (lR)-isomer. © 1985 IUPAC