Alkyl Group Migration in Ni-Catalyzed Conjunctive Coupling with C(sp³) Electrophiles: Reaction Development and Application to Targets of Interest

Abstract

A catalytic conjunctive cross-coupling reaction is developed that allows the construction of chiral organoboronic esters from alkylboron ate complexes and alkyl iodide electrophiles. The process occurs most efficiently with a Ni/Pybox-comprised catalyst and with an acenapthoquinone-derived boron ligand. Because of the broad functional group tolerance of this reaction, it can be a versatile tool for organic synthesis. Applications to the construction of (R)-coniine and (−)-indolizidine 209D are described.

Enantiomerically Enriched α-Borylzinc Reagents by Nickel-Catalyzed Carbozincation of Vinylboronic Esters

“…Also of note, while direct conjugate addition of the α-borylzinc reagent has not yet been accomplished, allylation product 28 can be oxidized to an equivalent product, γ-siloxy ester 38, by cobalt-mediated oxidation (Figure 3b). 21 That the carbozincation/trap sequence can accommodate unprotected methoxyamines allows the production of 24, which was found to be a substrate for an intramolecular stereospecific amination 22 reaction to give pyrrolidine derivative 39 (Figure 3c). In a short sequence, 39 could be converted to (−)-aphanorphine 23 (40) by Friedel−Crafts cyclization, palladium-catalyzed hydroxylation, 24 and LAH reduction.…”

Ni-Catalyzed Enantioselective Dialkyl Carbinol Synthesis via Decarboxylative Cross-Coupling: Development, Scope, and Applications

“…This is especially the case with substrates bearing near-identical alkyl side chains from the standpoint of sterics and electronics (Figure A). Thus, the most intuitive pathways such as kinetic resolution, asymmetric reduction, and nucleophilic addition to aldehydes are of little use in such contexts . Historically, polar bond disconnections have been employed to successfully access such molecules.…”

Asymmetric Conjugate Addition of Chiral Secondary Borylalkyl Copper Species

“…Next, the effect of boryl group (BY 2 ) on the enantio-and diastereoselectivity of this reaction was investigated. The reactions with 1 a-Bmac (mac = methylated acenaphthoquinone) [15] and 1 a-Bdan (dan = 1,8-diaminatonaphthalene) [16] instead of 1 a-Bpin yielded the corresponding addition products with 66:34 er and > 98:2 dr (entry 4) and 90:10 er and 88:12 dr (entry 5). With 1 a-Bdan and tBu-Josiphos ligand (L3) containing bulkier tBu groups on the phosphine, most promising results were obtained in terms of both enantio-and diastereoselectivity (95:5 er, 94:6 dr) (entry 6).…”