1,4‐Brook Rearrangement of β‐Silyl Allylic Alcohols: Trisubstituted Alkenes by Copper‐Mediated Stereoretentive ipso ‐Substitution Reactions

ABSTRACT When [Cp*Ru(MeCN) 3 ]PF 6 is used as the catalyst for the trans ‐hydrosilylation of propargyl alcohol derivatives, the silyl group is transferred with appreciable levels of regioselectivity to the alkyne C‐atom distal to the protic substituent. A copper‐mediated 1,4‐Brook rearrangement converts the resulting alkenylsilanes into alkenylcopper species, which can be intercepted with a multitude of carbon‐ or heteroatom‐based electrophiles; this formal ipso ‐substitution of the R 3 Si‐group allows a variety of trisubstituted olefins to be formed in stereodefined format, including fluoroalkenes and olefins bearing trifluoromethyl substituents. Best results are obtained with copper amides such as [Cu(NEt 2 )] 4 as the promoter in THF/DMPU; they are sufficiently basic to deprotonate the ─OH group in the first place, thereby triggering the critically important C‐to‐O silyl migration, yet mild enough to ensure compatibility with a variety of functional groups, including even C─H acidic sites adjacent to an ester or ketone. In cases where the trapping of the organocopper intermediates primarily formed is unduly slow or inefficient, the addition of either 2‐thienyllithium or tetra‐ n ‐butylammonium cyanide is recommended; these additives lead to more highly nucleophilic cuprate species that show the right reactivity profile for efficient coupling of otherwise noncompliant electrophilic partners.