Lithium Di-t-butylcuprate1

t-Bu2CuLi

[23402-75-7]  · C8H18CuLi  · Lithium Di-t-butylcuprate  · (MW 184.75)

(t-butylating reagent which undergoes conjugate addition reactions,1,2 1,2-addition reactions,3 substitution reactions,2b,4,5 carbocupration of alkynes,6 and oxidation reactions7)

Physical Data: dark red-brown to black solution; decomposes at 25 °C.1b

Solubility: sol Et2O, THF, pentane-Et2O-Me2S (1:1:1).

Preparative Methods: prepared in situ from CuI salts (Copper(I) Iodide,1b,5 Copper(I) Bromide1b) and complexes (CuBr.SMe28a and Copper(I) Iodide-Tributylphosphine7a) under an inert atmosphere of N2 or argon in Et2O or THF. Polymer-supported t-Bu2CuLi can be prepared.9 Preparation, stability and reactivity of organolithium- and organomagnesium-derived cuprate reagents and mixed hetero-t-butylcuprate reagents have been noted.1,4c,10,11 See Lithium Dimethylcuprate for purification of CuI salts.

Handling, Storage, and Precautions: air- and moisture-sensitive. Use in a fume hood.

Introduction.

Lithium di-t-butylcuprate displays the typical reactivity patterns of lithium diorganocuprates (see, e.g. Lithium Di-n-butylcuprate, Lithium Diethylcuprate, Lithium Dimethylcuprate, Lithium Diphenylcuprate, Lithium Di-n-propylcuprate).

Addition Reactions.

t-Bu2CuLi reacts with a,b-alkenyl ketones1,2,9 (mechanistic studies8), chiral esters12 (in the presence of Chlorotrimethylsilane) (eq 1), sulfoxides,13 N-tosyl-1-azoalkenes,14 ketoketenimines,15 and vinylphosphonium salts16 with conjugate transfer of the t-butyl ligand. Stereoselective cis addition can be achieved in the reaction of t-Bu2CuLi with a,b-alkynyl sulfones.17 Reaction of a,b-alkynyl trifluoromethyl ketones18 with t-Bu2CuLi affords mixtures of 1,2- and 1,4-addition products with modest regiocontrol; regioselective control can be obtained with the cyanocuprate reagent. Systems with extended conjugation, such as 3-alkynyl-2-cycloalkenones, undergo 1,6-addition.19

1,2-Addition of t-Bu2CuLi to a chiral g-alkoxy-a,b-enal3 occurs with vinylogous Cram stereoselectivity in the presence of t-Butyldimethylchlorosilane. Alkylated 3,4-dihydro-b-carbolines20 can be synthesized by 1,2-addition of t-Bu2CuLi to BF3 iminium salts.

Substitution Reactions.

t-Bu2CuLi effects substitution reactions with alkyl halides,2b,4,9 a-halo ketones,4b,21 alkyl tosylates,2b,4c,5,9 acetates,22 arene sulfonyl fluorides,23 and alkenyl substrates (e.g. vinyl triflates24 in the presence of Boron Trifluoride Etherate and enol phosphates25). Simple26a and alkenyl oxiranes11,26b-d undergo substitution reactions (eq 2); however, reactions of oxiranes with t-Bu2CuLi can be complicated by the formation of reduction products11 and mixtures of SN2- and SN2-type products.26c,d

Chiral a,b-alkenyl oxazolidines27 undergo allylic substitution reactions with t-Bu2CuLi. b-Aminocyclopentenyl sulfones28 participate in stereoselective syn-SN2 substitution with t-Bu2CuLi in modest yield (eq 3). Acyl halides4b and S-2-pyridyl thioates7c participate in nucleophilic acyl substitution reactions with t-Bu2CuLi to give ketones.

Carbocupration.

Acetylene undergoes a stereoselective syn carbocupration6 with t-Bu2CuLi and can be manipulated further in subsequent additions to a,b-alkenyl sulfones29 with retention of double bond configuration.

Oxidation Reactions.

Oxidative dimerization of t-Bu2CuLi proceeds poorly.7a Oxidative coupling of amines7b with t-Bu2CuLi affords t-butylated amines. Reaction of t-Bu2CuLi with S-2-pyridyl thioates7c in the presence of O2 gives esters.

Miscellaneous Reactions.

Reduction of 1,3-thiazole-5(4H)-thiones by electron transfer pathways can occur with t-Bu2CuLi.30 A vinylic bromide31 undergoes reduction-elimination reactions with t-Bu2CuLi. t-Bu2CuLi reduces gem-dihalocyclopropyl32 derivatives to give an intermediate copper species that can be alkylated. o-Halo-1-phenylalkynes33 are reduced by t-Bu2CuLi, affording an organocopper intermediate that can undergo intramolecular carbocupration (eq 4).

Related Reagents.

Copper(I) Iodide-Tributylphosphine; Lithium t-Butoxy(t-butyl)cuprate.


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Christopher W. Alexander & R. Karl Dieter

Clemson University, SC, USA



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