Construction of Multiple, Contiguous Quaternary Stereocenters in Acyclic Molecules by Lithiation-Borylation

Abstract

Lithiation of carbamates followed by borylation provides a powerful method for the homologation of boron reagents. However, when applied to hindered systems (secondary carbamates with tBu-boronic esters) for the construction of two quaternary centers, this methodology fails. Instead, using mixed boranes (tBuBMe2), the synthesis of adjacent quaternary stereogenic centers with full stereocontrol was successful. The process can be repeated two or three times in one pot leading to carbon chains bearing multiple contiguous quaternary stereogenic centers. The boranes were converted into tertiary alcohols or C-tertiary amines using chloramine. The origin of the high selectivity for alkyl over Me group migration was determined computationally.

Stereospecific Synthesis of Alkenes by Eliminative Cross‐Coupling of Enantioenriched sp3‐Hybridized Carbenoids

“…[13] Studies by Aggarwal et al have established that Hoppe-type lithiated carbamates are ar obust class of carbenoids for StReCH. [15] Given this precedent and wishing to eschew the targeting of easily made 1,2-disubstituted alkenes, we focused our experiments on the synthesis of 1-aryl-1,2dialkylethenes,aclass of styrenes that are difficult to prepare stereoselectively by traditional direct means. [15] Given this precedent and wishing to eschew the targeting of easily made 1,2-disubstituted alkenes, we focused our experiments on the synthesis of 1-aryl-1,2dialkylethenes,aclass of styrenes that are difficult to prepare stereoselectively by traditional direct means.…”

Synthesis of Adjacent Quaternary Stereocenters by Catalytic Asymmetric Allylboration

“…2b The bulkiness of the six substituents leads to a steric repulsion between the quaternary stereocenters. 5 This involves that the CC bond between the quaternary carbons is long 5 (typical CC bond lengths are 1.58-165 Å) and weak. Accordingly, CC bonds with adjacent quaternary carbons are difficult to form and easy to cleave.…”

Cyclopropene Derivatives as Precursors to Enantioenriched Cyclopropanols and n‐Butenals Possessing Quaternary Carbon Stereocenters

“…It should be noted that this single-pot strategy allows the formation of various combinations of quaternary carbon stereocenters in acyclics ystems (with alkyl, vinyl, phenyl groups). [22] Having established an easy protocol for the preparation of either 4 or 5 from simple starting materials, the enantioselective synthesis of the cyclopropenylmethyl ether 1d and cyclopropenylmethyl ester 1l were easily achieved in high enantiomeric ratio (e.r. 93:7) through cyclopropenation of the terminal alkyne with methyl phenyldiazoacetate and [Rh 2 (S-DOSP) 4 ]a st he catalyst (Scheme 3).…”