Studies on the Lithiation, Borylation, and 1,2-Metalate Rearrangement of O-Cycloalkyl 2,4,6-Triisopropylbenzoates.

A broad range of acyclic primary and secondary 2,4,6-triisopropylbenzoate (TIB) esters have been used in lithiation-borylation reactions, but cyclic TIB esters have not. We have studied the use of cyclic TIB esters in lithiation-borylation reactions and looked at the effect of ring size (3- → 6-membered rings) on the three key steps of the lithiation-borylation protocol: deprotonation, borylation and 1,2-metalate rearrangement. Although all rings sizes could be deprotonated, the cyclohexyl case was impractically slow, and the cyclopentyl example underwent α-elimination faster than deprotonation at -78 °C and so could not be used. Both cyclobutyl and cyclopropyl cases underwent rapid borylation, but only the cyclobutyl substrate underwent 1,2-metalate rearrangement. Thus, the cyclobutyl TIB ester occupies a "Goldilocks zone," being small enough for deprotonation and large enough to enable 1,2-migration. The generality of the reaction was explored with a broad range of boronic esters.

Asymmetric Synthesis of Tertiary Alcohols and Thiols via Nonstabilized Tertiary α-Oxy- and α-Thio-Substituted Organolithium Species.

Nonstabilized α-O-substituted tertiary organolithium species are difficult to generate, and the α-S-substituted analogues are configurationally unstable. We now report that they can both be generated easily and trapped with a range of electrophiles with high enantioselectivity, providing ready access to a range of enantioenriched tertiary alcohols and thiols. The configurational stability of the α-S-organolithium species was enhanced by using a less coordinating solvent and short reaction times.

Synthesis of 6- and 7-Membered N-Heterocycles Using α-Phenylvinylsulfonium Salts.

A concise synthesis of stereodefined C-substituted morpholines, piperazines, azepines, and oxazepines in moderate to excellent yields (27% to 75%) is reported by reaction of 1,2- or 1,3-amino alcohol/1,2- or 1,3-diamine with an α-phenylvinylsulfonium salt. High levels of regio- and diastereoselectivity (from 2:1 to >20:1) are observed through judicious choice of base (Cs2CO3) and solvent (CH2Cl2). Reactions are performed at ambient temperature and open to air and do not require anhydrous solvent. The deprotection of the N-sulfonamide protecting groups (N-Ts and N-Ns) is also demonstrated. Factors affecting regio- and diastereocontrol are discussed.