Benzylation of Imines with Activated Boronate Nucleophiles

Abstract

Benzylation reactions of N‐tosylimines and N‐tert‐butanesulfinyl imines using benzylboronic acid pinacol ester are reported. s‐Butyllithium was used to activate the boronic ester, rendering it nucleophilic. The reaction was compatible with electronically diverse substituents on the imine in both substrate classes. Good diastereoselectivity was observed in additions to N‐tert‐butylsulfinylaldimines. The diastereoselectivity observed in these reactions is consistent with an open transition state for the addition. Examples of a secondary alkylboronic ester nucleophile and a N‐tert‐butanesulfinyl trifluoromethylketimine electrophile are also included.

Difunctionalization of C–C σ-Bonds Enabled by the Reaction of Bicyclo[1.1.0]butyl Boronate Complexes with Electrophiles: Reaction Development, Scope, and Stereochemical Origins

“…The scope of the electro­phile was investigated using the bicyclo­[1.1.0]­butyl boronate complex of cyclo­hexyl­pinacol boronic ester ( 3 ) as the model intermediate (Figure ). First, in addition to benz­aldehyde ( 4 ), the reaction proceeded well using a range of carbonyl-containing functional groups and imines, including aceto­phenone ( 8 ), N -benzylidene­benezene­sulfonamide ( 9 ), N -benzylidene­diphenyl­phosphinic amide ( 10 ), benzoyl chloride ( 11 ), Troc-Cl ( 12 ), methyl cyano­formate (Mander’s reagent) ( 13 ), and α-iodo/bromo­aceto­phenone, the last of which underwent chemo­selective 1,2-addition of 3 to the ketone followed by a 3- exo -tet cyclization to deliver the corresponding epoxide 14 . Carbon dioxide could also be used as an electro­phile, reacting with boronate complex 3 to give carboxylic acid 15 in good yield and d.r.…”

“…28 borylcyclobutane 25 in good yield and as a single diastereomer. Finally, highly reactive electrophiles such as tropylium tetrafluoroborate (26), Eschenmoser's salt (27), and tosyl cyanide (28) were also successful electrophiles but gave lower diastereoselectivity with or without addition of a hydrogen bond donor. It is noteworthy that many of the electrophiles that have reacted successfully here, such as methanol, carbon dioxide and alkyl aldehydes, have never previously been reacted with boronate complexes of any type, highlighting the unique reactivity of bicyclo[1.1.0]butyl boronate complexes.…”

Transition Metal‐Free sp3−sp3 Carbon‐Carbon Coupling between Benzylboronic Esters and Alkyl Bromides

“…This approach is attractive in that it does not require the use of a transition metal eliminating the often‐toxic metal byproducts. We have demonstrated our dialkylboronate nucleophile reacts with aldehydes, aldimines and ketones [9–11] …”

“…The tertiary benzyl boronate reacted with 1‐bromoheptane in a 91 % yield of product 12 . Previously, tertiary nucleophiles had not been examined in our reaction development of nucleophilic benzyl additions to aldehydes, imines, and ketones [9–11] . The excellent yield obtained for product 12 makes this reaction an attractive method for forming bonds between a fully substituted benzylic nucleophile and primary electrophile.…”

“…We have demonstrated our dialkylboronate nucleophile reacts with aldehydes, aldimines and ketones. [9][10][11] There was an interest in identifying additional electrophiles compatible with our dialkylboronate intermediate in order to make sp 3 À sp 3 carbon-carbon bonds. Alkyl halides were chosen as electrophiles to pursue this type of bond formation.…”