cross-coupling could transform stereochemically complex small molecule synthesis into a simple and broadly accessible process. However, most current methods are not compatible with complex building blocks that represent densely packed, multistereogenic center-containing motifs commonly found in natural products and other complex targets. Here, we report a method that enables the α-methyl-β-hydroxyl motif, which is found in >18 000 natural products as well as other Csp 3 -rich organic fragments, to be embedded within stereochemically defined secondary alkyl boronic ester building blocks that are readily cross-coupled in a stereospecific manner. The steric effect-mediated decrease in reactivity toward transmetalation and deleterious side reactions associated with the cross-coupling of β-oxygen-containing Csp 3 boronic esters are concomitantly addressed using β-aryloxysilyl groups as dual-purpose transmetalation-promoting groups and stable β-oxygen surrogates. Mechanistic studies including real-time HPLC analysis show that a five-membered pinacol siloxaborolate generated in situ is then hydrolyzed to a dihydroxysiloxaborolate that acts as an activated transmetalation partner in a stereospecific process that proceeds with retention of configuration.