NiCl2 and NiCl2 = 6H2O: A very Useful Mild Lewis Acid in Organic Synthesis

Philippe Labrie

doi:10.1055/s-2003-36809

Synlett, Table of Contents

Synlett 2003(2): 0279-0280
DOI: 10.1055/s-2003-36809

SPOTLIGHT

NiCl₂ and NiCl₂ = 6H₂O: A very Useful Mild Lewis Acid in Organic Synthesis

Philippe Labrie*
Department of Chemistry, Universitè Laval, Quebec G1K 7P4, Canada
e-Mail: plabrie16@hotmail.com;

Abstract

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Biographical Sketches

P. Labrie was born in 1977, received his BSc degree in Chemistry (2000) from Laval University, Québec, Canada. Currently he is doing a PhD under the tutelage of Dr. René C.-Gaudreault, Laval University, Québec, Canada and Dr. Suman Rakhit, MCR Research Inc, Toronto, Ontario, Canada. His present research interest is the development of anticancer agents and inhibitors of P-glycoprotein. He is also investigating the application of Michael-type addition of arylboronic acids to enones derived from carbohydrates.

Introduction

Lewis acids are very useful reagents in organic synthesis. The classical Lewis acids currently used include BF₃ ·ΟEt₂, ZnCl₂, SnCl₂, TiCl₄ and many others. Nickel chloride can be also added to this list. NiCl₂ is a mild Lewis acid that promotes a wide variety of organic transformations in aqueous medium or organic solvent and may be used either catalytically or stoichiometrically. NiCl₂ was also used in a key step in the synthesis of bibenzopyran-4-ol, [1] tetrahydrodicranenone B [2] and Allopumiliotoxins. [3] NiCl₂ is a selective reductive agent when used with hydrides such as LiAlH₄ and NaBH₄. In fact, the mixture of NiCl₂ and NaBH₄ is used to prepare nickel boride, [4] a reducing agent for many functional groups: azide, [5] nitrile, [6] NO bond, [7] alkene [8] and haloalkane. [9] NiCl₂ was used in the regioselective rearrangement of dienols, [10] ring-opening of epoxide, [11] nickel(II)/chromium(II) chloride-mediated addition to aldehydes or ketones, [2] [3] Suzuki cross-coupling, [12] Biginelli reaction, [13] reductive Heck-like reactions, [14] nickel-catalyzed cross-coupling reaction of Grignard reagents [15] and homo-coupling reactions. [16]

Abstract


(A) Suzuki cross-coupling with ArBr and ArI can be carried out with PhB(OH)₂ in good yields using NiCl₂ ·6H₂O as a catalyst precursor. [12]
(B) NiCl₂-(1,3-butadiene) catalyzes the cross-coupling reaction of alkyl chlorides, bromides, and tosylates with Grignard reagents under mild conditions. [15]
(C) A general and convenient preparation of unsymmetrical N,N′-carbodiimides was achieved by the nickel(II)-catalyzed reaction of isocyanides with primary amines using molecular oxygen as an oxidant. [17]
(D) Aryl halides are readily homocoupled using a catalytic amount of NiCl₂/CrCl₂ and bipyridyl-type ligand 1 in the presence of manganese at room temperature in good yield. [16a]
(E) Azides are efficiently reduced to the corresponding amines with Sm/NiCl₂ ·6H₂O in excellent yields under mild conditions. [18]
(F) Nitriles are rapidly reduce to primary amines with nickel boride at room temperature. [6]
(F) A Biginelli reaction was efficiently used for the synthesis of 3,4-dihydropyrimidinones from aldehydes, β-keto esters and urea in ethanol, using NiCl₂ ·6H₂O. [13]
(G) An intramolecular Nozaki-Kishi cyclization was efficiently employed in the cyclization of Z-vinyl bromides to the corresponding cyclopentenols in good yields. [2]
(H) In the presence of moist alumina, aliphatic and aromatic alkenes were hydrogenated quantitatively to alkanes under mild conditions with NaBH₄/NiCl₂. [8]