[40575-23-3] · C6H9Cu · 3,3-Dimethyl-1-butynylcopper(I) · (MW 144.70)
(used in preparation of mixed cuprates; acts as weak nucleophile)
Alternate Names: t-butylethynylcopper(I); copper(I) t-butylacetylide.
Physical Data: orange solid; mp 80-150 °C (dec).
Solubility: sol ether, saturated hydrocarbons.
Preparative Methods: most conveniently prepared in situ by treatment of 3,3-dimethyl-1-butyne with n-Butyllithium, followed by addition of Copper(I) Iodide or the Me2S.CuBr complex (see Copper(I) Bromide).1,2 3,3-Dimethyl-1-butynylcopper(I) (1) can be isolated as a solid by addition of 3,3-dimethyl-1-butyne to a premixed solution of Copper(II) Sulfate and Hydroxylamine hydrochloride in aqueous ammonia. The aqueous layer is decanted and the precipitate is extracted with pentane. After workup, (1) is collected upon concentration of the solvent. Alternatively, (1) has been prepared by photoreduction of Copper(II) Acetylacetonate in the presence of 3,3-dimethyl-1-butyne.3
Handling, Storage, and Precautions: air and moisture sensitive. Use in a fume hood.
Alkynyl organocopper reagents are weak nucleophiles; however, (1) will react with pivaloyl chloride to give 2,2,6,6-tetramethyl-4-heptyn-3-one (2) in 69% yield (eq 1).4 The more reactive higher-order cuprate (3), formed from (1) and 2 equiv of lithium t-butylacetylide, transfers a t-butylacetylene group to phosphonoamine (4), affording alkynylamine (5) in 60% yield (eq 2).5
Other attempts at electrophilic transfer of a t-butylacetylene group are not as successful. Treatment of (1) with Cyanogen Bromide does not produce the desired nitrile (6); instead, bis-alkyne (7) is the only product isolated (eq 3).6 The cuprate prepared from (1) and butylmagnesium bromide reacts slowly with benzoyl chloride, affording only a moderate yield (28%) of ketone (8) (eq 4).7
The title reagent is most commonly used for the in situ preparation of mixed cuprates. Alkynes bind tightly to copper, allowing selective transfer of a synthetically valuable primary, secondary, or vinylogous lithium reagent.1,8 The t-butylacetylene ligand offers several advantages, including good solubility in ether and THF, thermal stability allowing reactions to be run at 0 °C, and volatile, easily removed byproducts. The first examples demonstrated the transfer of methyl and vinyl substituents to isophorone (9) (eq 5).1 More complex groups include the a-acrolein anion equivalent (12), which adds in 1,4-fashion to enones in excellent yields (eq 6).9,10
Mixed cuprates derived from (1) have been used in natural product total synthesis. 1,4-Addition of the cyclopropylcuprate (14) to 2-cyclohexen-1-one provided adducts (15) and (16) in a 3.1:1 ratio in 45% yield (eq 7). The threo adduct (15) can then be converted to (±)-threo-juvabione (17) in several steps.11 The 1-heptenyl cuprate (19) reacts with primary iodide (18) to give alkene (20), with complete retention of the cis stereochemistry, in 36% yield with a 25% recovery of (18). Intermediate (20) can then be taken forward in a synthesis of LTB4 (21) (eq 8).12
Matthew E. Voss
The Du Pont Merck Pharmaceutical Company, Wilmington, DE, USA