Lithium n-Butyl(3-methoxy-3-methyl-1-butynyl)cuprate

(1; R = n-Bu)

[66777-74-0]  · C10H18CuLiO  · Lithium n-Butyl(3-methoxy-3-methyl-1-butynyl)cuprate  · (MW 224.77) (2; R = t-Bu)


(mixed cuprate butyl transfer agents)

Preparative Methods: these reagents are prepared in situ by deprotonation of 3-methoxy-3-methyl-1-butyne with n-Butyllithium, followed by addition of Copper(I) Iodide and then either t-Butyllithium or n-butyllithium.1

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

Butyl Transfer Agents.

The less expensive 3-methoxy-3-methyl-1-butyne was introduced as an alternative to t-butylacetylene for mixed cuprate reactions. Cuprates synthesized using this reagent maintain the same solubility profile, thermal stability, and ligand transfer preferences as obtained using t-butylacetylene. Lithium n-butyl(3-methoxy-3-methyl-1-butynyl)cuprate (1) underwent displacement reactions with cyclohexyl iodide and cinnamyl bromide in moderate yield, but produced a quantitative yield upon 1,4-addition to 2-cyclohexen-1-one. The much more sterically hindered lithium t-butyl(3-methoxy-3-methyl-1-butynyl)cuprate (2) also underwent 1,4-addition to 2-cyclohexen-1-one in excellent yield (eqs 1-4).1

Reagent (1) was used to study the reaction of cuprates with a-oxoketene dithioacetals.2 Reaction of (1) with (3) gave a 92:8 (E)/(Z) ratio of addition products (4) in 55% yield, along with a 12% yield of reduction product (5) and 38% recovered (3) (eq 5). When (1) was reacted with the a-oxoketene dithioacetal (6) only the addition product (7) (89:11 E/Z) was obtained in 93% yield (eq 6).

During a study of the effects of trimethylsilyl halides on the structure and reactivity of higher order (HO) cuprates, it was discovered that addition of 2 equiv Chlorotrimethylsilane irreversibly transformed the HO cuprate (8) (R = Me) into the lower order (LO) cuprate (9) and 1 equiv Cyanotrimethylsilane and LiCl (eq 7).3 To determine if (9) was the reactive intermediate, TMSCl, TMSCN, and LiI were added to a solution of (1). 1,2-Addition to aldehyde (10) produced alcohols (11) and (12) in a 10-12:1 (syn:anti) ratio in high chemical yield (eq 8). This is analogous with the results obtained from reaction of (10) with HO cuprates using TMSX (X = Cl, Br, I, OTf) as an additive. No reaction between (1) and TMSCl could be detected by 1H, 7Li, or 29Si NMR, leaving the role of TMSX in these reactions somewhat elusive.

Related Reagents.

3,3-Dimethyl-1-butynylcopper(I); (3-Methoxy-3-methyl-1-butynyl)copper(I).

1. Corey, E. J.; Floyd, D.; Lipshutz, B. H. JOC 1978, 43, 3418.
2. Dieter, R. K.; Silks, L. A., III; Fishpaugh, J. R.; Kastner, M. E. JACS 1985, 107, 4679.
3. Lipshutz, B. H.; Ellsworth, E. L.; Siahaan, T. J.; Shirazi, A. TL 1988, 29, 6677.

Matthew E. Voss

Du Pont Merck Pharmaceutical Company, Wilmington, DE, USA

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