[58384-87-5] · C14H26CuLiO4 · Lithium Bis(3,3-diethoxy-1-propen-2-yl)cuprate · (MW 328.85)
(organocopper reagent for the transfer of a protected acrolein group to allyl halides, vinyl epoxides, and carbonyl compounds; reagent for the construction of a-methylene-g-butyrolactones)
Physical Data: thermally unstable organocuprate generated between -60 and -70 °C; stable and reactive at temperatures below -40 °C.
Solubility: sol THF at -40 °C or below.
Preparative Method: from the reaction of 2-Lithio-3,3-diethoxy-1-propene2 with Me2S complex of Copper(I) Bromide at -60 to -70 °C in THF.
Handling, Storage, and Precautions: should be generated in the absence of O2 and moisture at low temperatures under an N2 or Ar atmosphere.
The generation of the title reagent (1)1 is straightforward at -70 °C (eq 1). In addition to the homocuprate (1) a mixed cuprate containing a t-butyl-alkynyl ligand may also be prepared at -40 °C.1
This cuprate (1) is the one organometallic reagent in the highest oxidation state capable of adding an acrolein and hence an acrylate unit in a conjugate addition to enones. In a typical example, (1) adds 1,4 to carvone at -70 °C to produce the adduct (2) (eq 2). Hydrolysis of (2) and mild oxidation with Silver(I) Oxide produces the acrylic acid (3) (eq 3).1
In a total synthesis of (+)-hanegokedial, a modified version of reagent (1) was added in a 1,4-manner to the cycloheptenone (4) to prepare a 2:1 mixture of stereoisomers of adduct (5) in 84% yield. In this example the copper enolate intermediate was trapped with gaseous Formaldehyde (eq 4).3
The direct alkylation of 3-bromocycloheptene with (1) produces the adduct (6) in 60% yield at -40 °C. The adduct (6) was a convenient precursor to an acrylic acid (7) and iodolactone (8) (eq 5).4
While the title reagent reacted well with allylic halides, it did not react with allylic acetates. All attempts to open simple epoxides with (1) also failed at various temperatures below 0 °C.4
Reactions of the cuprate (1) with monoepoxides of cyclic 1,3-dienes yielded mixtures of 1,2 and 1,4 ring-opened products, with the former as the major products.5 The ratio of 1,2 to 1,4 products varied slightly depending on whether THF or ether was used as a reaction solvent. In the case of cyclopentadiene monoepoxide in THF, the yield of adducts was 87% with a 1,2:1,4 ratio of 7:3 (eq 6).
The best regioselectivity found for an epoxide opening was for the cycloheptadiene monoepoxide system which produced a 1,2:1,4 ratio of 3:1 in THF and 6:1 in diethyl ether (eq 7).
The 1,2-adduct (9) could be transformed into a trans-a-methylenebutyrolactone (11) or a cis-a-methylenebutyrolactone (12) (eq 8).5
Joseph P. Marino & David P. Holub
University of Michigan, Ann Arbor, MI, USA