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Versatile route to chiral alkylboronate esters

Compounds feature boron bound to a stereogenic carbon, could help chemists who make drugs

by Bethany Halford
December 8, 2016

scheme showing how Fu’s group made chiral boronate esters from a cholesterol derivative
A green dot indicates the stereogenic carbon Fu’s group generated when making this boronate ester from a cholesterol derivative. The team made both diastereomers using different chiral ligands.

Organoboron compounds have long been a favorite tool of organic chemists. For example, they are one of the reaction partners in the wildly popular Suzuki cross-coupling reaction, wherein palladium catalyzes the formation of a new C–C bond between the organic groups of an organoboron compound and an organohalide. If the organoboron compound is chiral, it can maintain its configuration during the cross-coupling. Because chirality is so important in drugs and other medicinally relevant molecules, chemists have been trying to find ways to create chiral organoboron compounds.

Caltech chemists led by Gregory C. Fu now report a versatile asymmetric way to make alkylboronate esters (Science 2016, DOI: 10.1126/science.aai8611). Unlike previous methods, many of which relied on stoichiometric amounts of chiral reagents, their reaction uses a nickel catalyst with a chiral ligand to couple racemic α-haloboronates with organozinc reagents.

“We’re starting with a racemic mixture and we’re converting both enantiomers in the starting material into a single enantiomer in the product,” Fu explains.

He adds that it was important to develop a method that could be used to make a wide range of alkylboronate esters. To that end, because the reaction uses mild organozinc reagents instead of harsh organolithiums or Grignard reagents, the chemists can make chiral alkylboronate esters that have otherwise sensitive functional groups, such as esters and cyano groups.

“What we think is especially powerful here is the fact that the reaction is generating such a useful and important class of molecules with high enantiomeric purity,” Fu says.

Milton R. Smith III, an expert in organoboron chemistry at Michigan State University and cofounder of the specialty chemical maker BoroPharm, says the work represents “a very important advance in making optically active organoboron compounds more accessible.”



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