Experimental and theoretical evidence is reported for a rare type I dyotropic rearrangement involving a [1,2]-alkene shift, leading to the regio- and stereospecific ring contraction of bromocycloheptenes. This reaction occurs under mild conditions, with or without a Lewis acid catalyst. DFT calculations show that the reaction proceeds through a nonclassical carbocation–anion pair, which is crucial for the low activation barrier and enantiospecificity. The chiral cyclopropylcarbinyl cation may be a transition state or an intermediate, depending on the reaction conditions.

The highly regio- and enantioselective (up to >99:1 dr, up to 99:1 er) desymmetrization of meso-1,4-dibromocycloalk-2-enes using asymmetric allylic substitution with organolithium reagents to afford enantioenriched bromocycloalkenes (ring size of 5 to 7) has been achieved. The cycloheptene products undergo an unusual ring contraction. The synthetic versatility of this Cu(I)-catalyzed reaction is demonstrated by the concise stereocontrolled preparation of cyclic amino alcohols, which are privileged chiral structures in natural products and pharmaceuticals and widely used in synthesis and catalysis.

A highly enantioselective copper/N-heterocyclic carbene catalyzed allylic arylation with organolithium compounds is presented. The use of commercial or readily prepared aryllithium reagents in the reaction with allyl bromides affords a variety of chiral diarylvinylmethanes, comprising a privileged structural motif in pharmaceuticals, in high yields with good to excellent regio- and enantioselectivities. The versatility of this new transformation is illustrated in the formal synthesis of the marketed drug tolterodine (Detrol).

All reactions were carried out under nitrogen atmosphere in oven-dried glassware using standard Schlenk techniques. All allylic substitution reactions were performed in an ethanol bath cooled to -80 °C using a cryostat. Dichloromethane, diethyl ether, tetrahydrofuran and toluene were dried via a solvent purification system (MBRAUN SPS systems, MB-SPS-800).

An efficient one-pot synthesis of optically active β-alkyl-substituted alcohols through a tandem copper-catalyzed asymmetric allylic alkylation (AAA) with organolithium reagents and reductive ozonolysis is presented. Furthermore, hydroboration-oxidation following the Cu-catalyzed AAA leads to the corresponding homochiral γ-alkyl-substituted alcohols.