Diethylzinc

Introduction

Diethylzinc (ZnEt₂, bp = 118 °C at 760 mmHg) is an inexpensive and commonly used diorganozinc reagent.[1] Due to its high pyrophoric nature, diethylzinc is often commercialized as a solution in organic solvent (hexane, toluene, or heptane).

ZnEt₂ was first synthesized by Frankland in 1849 by heating ethyl iodide with zinc metal.[2] To facilitate purification, other methods have been developed, such as the transmetalation of a zinc halide with an organometallic reagent.[3] The use of this reagent has gained attention thanks to its application in asymmetric synthesis.

Diethylzinc is a versatile nucleophile that is suited for metal catalysis due to the highly covalent character of the carbon–zinc bond and the low Lewis acidity of zinc(II). Moreover, the empty low-lying p-orbitals allow facile transmetalation reactions.

Abstracts

(A) 1,2-Addition: Seebach and co-workers reported the 1,2-addition of diethylzinc to aliphatic and aromatic aldehydes in the presence of Ti(Oi-Pr)4 and TADDOL derivatives as ligands, which led to enantiopure alcohols in good yields.[4] Walsh and co-workers described also the synthesis of tertiary alcohols by the asymmetric addition of ZnEt2 to ketones catalyzed by a titanium catalyst with a chiral diamine ligand.[5]
(B) 1,4-Addition to Cyclic Enones: Alexakis and co-workers reported an asymmetric copper-catalyzed 1,4-addition of diethylzinc to cyclic enones using a phosphoramidite ligand, followed by C-enolate trapping resulting in the synthesis of α,β-disubstituted ketones with a high degree of stereoselectivity.[6]
(C) 1,4-Addition to Reactive Acceptors: Carreira and co-workers developed the copper-catalyzed highly stereoselective conjugate addition of diethylzinc to Meldrum’s acid derived acceptors with phosphor­amidite ligands.[7]
(D) Addition to α-Chloro Aldimines: Walsh and co-workers described a highly diastereoselective synthesis of α-chloro amine via a nucleophilic addition to α-chiral imine derivatives that proceeds through an unusual chelation transition state instead of a Cornforth–Evans model.[8]
(E) Addition to N-Acylpyridinium Salts: Feringa and Minnaard ­developed a catalytic enantioselective addition of diethylzinc to N-acylpyridinium salts with good yields and excellent enantioselectivities. This method was applied to the synthesis of natural alkaloids.[9]
(F) Marshall Homopropargylation: Taking advantage of zinc(II)’s ability to perform transmetalation, allenyl zinc compounds were synthesized from diethylzinc. Then, addition to an aldehyde gave the desired anti homopropargylic alcohol adducts with high de. ­Marshall and co-workers synthesized various enantioenriched homopropargylic alcohols and applied this method to the synthesis of superstolide A.[10]
(G) Alkyl Radical Addition: Stereoselective synthesis of diethyl fumarate derivatives was accomplished under mild conditions via a direct anti carbozincation of diethyl acetylenedicarboxylate through diethylzinc-mediated alkyl radical addition.[11]
(H) Phenyl Transfer to Aldehydes: Bolm and co-workers have shown that in the synthesis of diarylmethanol compounds the use of diethylzinc can improve the enantioselectivity of the reaction.[12]
(I) Simmons–Smith Reaction: ZnEt2 was also used in asymmetric Simmons-Smith reactions.[13] This reaction was employed in many syntheses of natural products: for instance in 2008, Willis and co-workers described the synthesis of (−)-clavosolide D: [14] treatment of the allylic alcohol with Et2Zn and CH2ICl led to the formation of a cyclopropane with excellent yield and diastereoselectivity.
(J) Enantioselective Allylic Substitution: In 2009, the group of ­Hoveyda reported that chiral N-heterocyclic carbene complexes are efficient catalysts in the copper-free enantioselective allylic alkylation using diethylzinc and allylic phosphates. This reaction led to enantioenriched allylic moieties with quarternary centers.[15]

• References

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• 4c For addition of ZnEt₂ to aldehydes catalyzed by BINOLs derivatives, see: Pu L. Acc. Chem. Res. 2014; 47: 1523
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