Ketone Synthesis from Benzyldiboronates and Esters: Leveraging α-Boryl Carbanions for Carbon–Carbon Bond Formation

Abstract

An alkoxide-promoted method for the synthesis of ketones from readily available esters and benzyldiboronates is described. The synthetic method is compatible with a host of sterically differentiated alkyl groups, alkenes, acidic protons α to carbonyl groups, tertiary amides and aryl rings having common organic functional groups. With esters bearing α-stereocenters, high enantiomeric excess was maintained during ketone formation, establishing minimal competing racemization by deprotonation. Monitoring the reaction between benzyldiboronate and LiO t Bu in THF at 23 °C allowed for the identification of products arising from deborylation to form an αboryl carbanion, deprotonation, and alkoxide addition to form an "-ate" complex. Addition of 4trifluoromethylbenzoate to this mixture established the x-boryl carbanion as the intermediate responsible for C-C bond formation and ultimately ketone synthesis. Elucidation of the role of this intermediate leveraged additional bond-forming chemistry and enabled the one-pot synthesis of ketones with α-halogen atoms and quaternary centers with four-different carbon substituents.

Copper-Catalyzed Enantiotopic-Group-Selective Allylation of gem-Diborylalkanes

“…Increasing the reaction temperature to 50 °C shortened the reaction time (12 h), even though 3c was obtained in a slightly decreased er (entry 14). Using NaO t Bu (entry 15) or KO t Bu (entry 16) instead of LiO t Bu gave 3c in low to poor er, probably because of the competitive S N 2 reaction of 1e with in situ generated α-borylcarbanion . The absolute stereochemistry of the major enantiomer of 3c was determined as S after oxidation of B­(nep) to a known compound…”

Exploring benzylic gem-C(sp3)–boron–silicon and boron–tin centers as a synthetic platform

“…A second approach was also developed starting with a commercial benzylboronate core via deprotonation using a hindered lithium 2,2,6,6-tetramethylpiperidide base (Li-TMP), followed by the addition of a chlorosilane. 10 This route was convenient for producing derivatives with silyl groups other than SiMe 3 , such as the gem -SiEt 3 species 1b (84%, Scheme 2 , approach B) or the Si( t Bu)Me 2 analogue 1c (60%). Finally, when a suitable B- or Si-benzylic precursor was not readily available, a Matteson-type homologation 9 c of several Ar–Bpin species with an in situ generated Me 3 Si(Cl)CH–Li reagent was found to proceed smoothly.…”

Borata‐Alkene Species as Nucleophilic Reservoir

“…Their methodology is based on the activation of 1,1‐diborylalkanes with MeLi, to generate α‐monoboryl carbanions that react with the carboxylic acids providing mono‐, di‐ and tri substituted ketones. More recently, Chirik and co‐workers, established the formation of α‐boryl carbanionic species, through deborylative pathways with LiO t Bu in THF at 23 °C, which interact with esters for C−C bond formation and ultimately ketone synthesis [88c] . Garratt and Pattison have recently reviewed the preparation of enolates by the addition of lithiated geminal bis(boron) compounds to esters which can be subsequently trapped with two equivalents of halogen and alkyl electrophiles to yield α,α‐difunctionalized compounds [89]…”