5-Aryltetrazoles from Direct C-H Arylation with Aryl Bromides.

A mild, direct C-H arylation of 1-substituted tetrazoles to 5-aryltetrazoles is developed using a Pd/Cu cocatalytic system with readily available aryl bromides. The methodology avoids late-stage usage of azides and tolerates a wide range of functionalities.

Optimization of Reaction and Substrate Activation in the Stereoselective Cross-Coupling of Chiral 3,3-Diboronyl Amides.

A method has been developed for the chemo- and stereoselective Suzuki-Miyaura cross-coupling of optically enriched gem-diboronyl compounds with various aryl bromides. Experimental evidence suggests that the Lewis acidity of the second boron group in these substrates plays a significant role in facilitating these otherwise challenging cross-coupling processes. ß-Diboronyl esters may be successfully cross-coupled in excellent yield and enantiomeric excess with prior conversion of the pinacol boronate to the corresponding trifluoroborate salt. In contrast, a substrate bearing a Weinreb amide can undergo direct coupling of the Bpin moiety, likely due to the stronger coordination of the more basic amide carbonyl group. The resulting optically enriched secondary boronate may be used in a second enantioselective cross-coupling to afford pharmaceutically relevant diarylmethane products. The use of a Weinreb amide substrate allows for facile postcoupling modification, as demonstrated by a transformation to the corresponding ketone.

Chiral boronate derivatives via catalytic enantioselective conjugate addition of Grignard reagents on 3-boronyl unsaturated esters and thioesters.

There is a growing interest in the development of new methods to prepare chiral organoboronate derivatives in optically pure form. An efficient copper-catalyzed enantioselective conjugate addition methodology using Grignard reagents and 3-boronyl acrylate derivatives was optimized for the preparation of chiral alkylboronate products in high yields and up to 98% ee. The resulting 1,8-diaminonaphthalene adducts can be transformed into the corresponding boronic acid, pinacol boronate, and trifluoroborate salt. This method extends the realm of chemical reactions compatible with useful boron-containing substrates.

Stereoselective preparation of ß-aryl-ß-boronyl enoates and their copper-catalyzed enantioselective conjugate reduction.

A new methodology has been developed for the stereoselective preparation of ß-aryl-ß-boronyl α,ß-unsaturated esters via Heck coupling, and their subsequent copper(I)-catalyzed enantioselective conjugate reduction. Various chiral secondary boronate derivatives can be accessed in excellent yields and good to high levels of enantioselectivity through the efficient copper-catalyzed process using polymethylhydrosiloxane (PMHS) as the hydride source.

Enantioselective preparation and chemoselective cross-coupling of 1,1-diboron compounds.

The simplicity, efficiency and generality of the transition-metal-catalysed Suzuki-Miyaura cross-coupling reaction has led to its application in the preparation of a wide variety of organic compounds. Cross-coupling of alkylboron derivatives, however, remains a major challenge, in particular with regard to stereochemical control. Here, we describe the preparation and reaction of highly optically enriched 1,1-diboron compounds. A catalytic asymmetric conjugate borylation of ß-boronylacrylates provided geminal diboronate products that feature two distinct boronyl units, in 99% enantiomeric excess. Chemoselective cross-coupling of one-boronyl unit, a trifluoroborate salt, occurred stereospecifically via inversion of its configuration to generate enantioenriched benzylic or allylic boronates. The difficult transmetallation in the Suzuki-Miyaura catalytic reaction cycle is believed to be facilitated by a stabilization effect from the second boronyl unit, and internal coordination by the oxygen of the proximal carboxyester. We also explored subsequent functionalization of the second boronyl unit.