Diastereoselective Intramolecular Carbolithiations of Stereodefined Secondary Alkyllithiums Bearing a Remote Alkynylsilane.

Various secondary alkyl iodides bearing a remote alkynylsilane underwent intramolecular carbolithiations triggered by an I/Li-exchange performed at -100 °C using t-BuLi (2.5 equiv). The resulting alkenyllithiums were stereoselectively converted to tetrasubstituted cyclopentane exo-alkylidenes. After Pd-catalyzed hydrogenation, cyclopentanes and cis-bicyclo[4.3.0]nonanes were obtained with stereocontrol of four contiguous centers.

Iterative reactions of transient boronic acids enable sequential C-C bond formation.

The ability to form multiple carbon-carbon bonds in a controlled sequence and thus rapidly build molecular complexity in an iterative fashion is an important goal in modern chemical synthesis. In recent times, transition-metal-catalysed coupling reactions have dominated in the development of C-C bond forming processes. A desire to reduce the reliance on precious metals and a need to obtain products with very low levels of metal impurities has brought a renewed focus on metal-free coupling processes. Here, we report the in situ preparation of reactive allylic and benzylic boronic acids, obtained by reacting flow-generated diazo compounds with boronic acids, and their application in controlled iterative C-C bond forming reactions is described. Thus far we have shown the formation of up to three C-C bonds in a sequence including the final trapping of a reactive boronic acid species with an aldehyde to generate a range of new chemical structures.

Stereoselective Retentive Domino Transmetalations of Secondary Alkyllithium Compounds to Functionalized Secondary Alkylcopper Reagents.

Functionalized secondary alkyllithium reagents obtained by I/Li exchange from the corresponding secondary alkyl iodides undergo two successive transmetalations with Me3 SiCH2 ZnBr⋅LiBr and CuBr⋅2 LiCl⋅Me2 S to provide functionalized secondary alkylcopper compounds with high retention of configuration. These alkylcopper derivatives react further with electrophiles such as alkynyl esters, acid chlorides, allylic chlorides, ketals, ethylene oxide, and 3-iodocyclopentanone with high retention of configuration. A related sequence of transmetalations with MeMgI and LaCl3 ⋅2 LiCl allows a retentive addition of secondary alkyllithium reagents to acetone. The influence of the solvent on the configurational stability of secondary alkylzinc reagents is described.

Stereoselective synthesis and reactions of secondary alkyllithium reagents functionalized at the 3-position.

Secondary alkyllithium reagents bearing an OTBS group (TBS=tert-butyldimethylsilyl) at the 3-position can be prepared stereoconvergently through an I/Li exchange from a diastereomeric mixture of the corresponding secondary alkyl iodides. These lithium reagents react with a range of electrophiles, including carbon electrophiles, with retention of configuration to yield various 1,3-difunctionalized derivatives with good diastereoselectivities. Kinetic studies show that the 3-siloxy group strongly accelerates the epimerization at the lithium-substituted carbon atom. This method offers a new way to construct chiral open-chain molecules with excellent stereoselectivity.