Nickel-Catalyzed Alkylation or Reduction of Allylic Alcohols with Alkyl Grignard Reagents

Abstract

By choosing different phosphine ligands, nickel-catalyzed selective alkylation and reduction of allylic alcohols with alkyl Grignard reagents were performed. The reaction using Ni­(dppe)­Cl2 as the catalyst resulted in the cross-coupling of allylic alcohols with primary alkyl Grignard reagents and cyclopropylmagnesium bromide. The reaction catalyzed by the combination of Ni­(PCy3)2Cl2 and dcype led to the reduction of allylic alcohols. Secondary alkyl Grignard reagents except cyclopropylmagnesium bromide always led to reduction of allylic alcohols using either Ni­(dppe)­Cl2 or Ni­(PCy3)2Cl2/dcype as the catalyst. In the reductive reaction β-H-containing alkyl Grignard reagents were required.

Late‐Stage Chemoenzymatic Installation of Hydroxy‐Bearing Allyl Moiety on the Indole Ring of Tryptophan‐Containing Peptides

“…The presence of HBA enabled the synthesis of complex molecules such as the antibiotic precursor 6‐deoxyerythronolide [7] and the polyene pheromone navenone B [8] from late‐stage intermediates. Moreover, the presence of HBA facilitated impressive downstream chemical reactions such as Sharpless epoxidation, [9] intramolecular cyclization, [10] and rearranged enone formation, [11] in addition to alkylation [12] and chlorination [13] reactions. The installation of HBA is challenging and has been achieved via hydroxylation of compounds containing allylic groups in multi‐step reactions [14] .…”

Nickel‐Catalyzed Allylic Substitution Reactions: An Evolving Alternative

“…[11] Debasish Ghorai received his BSc in Science from Vidyasagar University (India Recently the Wang group reported a detailed study on ligand-controlled Ni-catalyzed allylic substitution reactions involving simple allylic alcohols and alkyl Grignard reagents, which afforded either an alkylation or reduction type product in good to excellent yields by employment of either Ni(dppe)Cl 2 or a mixture of Ni(PCy 3 ) 2 Cl 2 and dcype, respectively (Scheme 4). [12] The authors proposed that the reaction proceeds through a Ni(0)/Ni(II) pathway in which the initial Ni(II) species is reduced to Ni(0) by the Grignard reagent followed by oxidative addition of allyloxo-magnesium leading to a mixture of η 3 -and η 1 -allyl nickel intermediates (Int-1 & Int-2). Subsequent transmetalation with alkyl Grignard reagents leads to another set of η 3 -and η 1 -allyl nickel intermediates (Int-3 & Int-4).…”

Transition-Metal-Catalyzed Cross-Coupling Reactions of Grignard Reagents

“…Using NiCl 2 (dppe) gave the cross-coupling product 37, however, the combination of NiCl 2 (PCy 3 ) 2 and dcype afforded the reduction product 38. 46 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.…”