[110769-32-9] · C17H22CuLi2NSi2 · Dilithium Cyanobis(dimethylphenylsilyl)cuprate · (MW 373.97)
(higher-order copper reagent for transfer of a dimethylphenylsilyl group to enones, allenes, alkynes, epoxides, and alkyl halides)
Physical Data: relatively stable reagent at rt; usually prepared in situ at 0 °C.
Solubility: sol THF (-78 °C and above).
Preparative Methods: prepared1 by adding 0.5 equiv of dry Copper(I) Cyanide to dimethylphenylsilyllithium in THF (eq 1), which in turn is generated from Chlorodimethylphenylsilane and Lithium metal. Analogous bis(trimethylsilyl)cyanocuprates are prepared in a similar manner.
Handling, Storage, and Precautions: cannot be stored or isolated. Care must be taken to avoid oxygen and moisture in the reaction system. Use in a fume hood.
Low-temperature 29Si, 13C, and 1H NMR spectroscopic techniques have been used to probe the nature of these higher-order cuprates.2 These studies showed conclusively the facile dissociation-reassociation of ligands on copper. In the presence of Methyllithium, dimethylphenylsilyllithium, and copper(I) cyanide, a mixed metallocuprate is formed (eq 2). The metallocuprate (2) preferentially transfers the dimethylphenylsilyl group to enones and 1-alkynes.
In general, the reactivities of lower-order and higher-order cyano silylcuprates are very similar toward a,b-unsaturated ketones in ether (eq 3).2 In some cases, as with alkynic esters, a higher-order reagent gives higher yields and greater stereoselectivity at -78 °C. When the bis(trimethylsilyl)cyanocuprate (3) was added to ethyl 2-butynoate, a high yield of only the (E)-isomer was obtained (eq 4).3
With cyclohexenone, the corresponding lower-order cuprate gave a 58% product yield and, in the case of eq 4, a mixture of (E/Z) adducts was observed with the corresponding lower-order cuprate. Interestingly, the mixed (dimethylphenylsilyl)(methyl)cyanocuprate (2) gave the highest yield (94%) of adduct with cyclohexenone.
Higher-order silyl cuprates such as (1) add regioselectively to terminal alkynes in a cis fashion, and the intermediate vinylcopper species (4) may be trapped with electrophiles to give 2,2-disubstituted vinylsilanes (5) (eq 5).1,2 Corresponding reactions with the lower-order cuprate of reagent (1) give low yields of regioisomeric vinylsilanes upon protonation.4
Typical electrophiles (E+) that have been employed are ammonium chloride for protonation (94% yield), Iodomethane (71%), cyclohexenone (54%), and Propylene Oxide (89%). An example of trapping a vinylcopper species with an ethyl acrylate precursor is shown in eq 6 for the synthesis of the vinylsilane (6).4,5
As a type of activated alkene, allenes undergo silylcupration with reagent (1) to give either vinyl- or allylsilanes.6 Simple alkylallenes react quickly at -78 °C to give allylsilanes cleanly (eq 7). In this case the silyl group is transferred to the less substituted carbon of the allene.
With allene itself or terminal allenes the regioselectivity is reversed and vinylsilanes are the major products.7,8 In these cases an intermediate allylcuprate (7) is generated which can be quenched with electrophiles such as Chlorine, Acetyl Chloride, or a proton to give products (8), (9), and (10), respectively (eq 8).
Intermediate (7) (R = H) behaves abnormally when reacted with cyclohexenone and iodine. In the former case, 1,2-addition, and not conjugate addition, prevails; in the latter case, an unusual rearrangement occurs to form the 2-iodoallylsilane (11) (eq 9).
Previously, the reactions of reagents (1) and (3) with 3,3-dimethylallene were reported to give the allylsilane adduct (12) initially which, upon trapping with cyclohexenone and acetyl chloride, produced the expected adducts (13) and (14), respectively (eq 10).9
The reactions between oxabicyclo[3.2.1]octenones and reagent (1) and its lower-order analog have been studied.10 Silylcupration of 8-oxabicyclo[3.2.1]oct-6-en-3-one (15) with (1) is rapid and is followed by a slower step involving trapping onto the carbonyl group at C-3 to give a ring-closed cyclobutanol product (16) along with some of the protonated ketone (17) (eq 11).
Silylcupration of a-methyl substituted derivatives of (15) produced intermediates (18) which undergo such slow ring closure onto the ketone that (18) could be trapped with electrophiles (MeI or H+). In an unusual oxidation process, treatment of intermediate (18) (R1 = R2 = Me) with dry silica gel produced the b-hydroxysilane (19) in quantitative yield (eq 12). Product (19) easily undergoes a base-catalyzed Peterson alkenation to the starting alkene.
In summary, the higher-order silyl cuprates (1) and (3) tend to be more reactive and more nucleophilic than their lower-order counterparts in silylcuprations and SN2-like displacements. Both classes of reagents are fairly stable up to ambient temperatures.
Joseph P. Marino & David P. Holub
The University of Michigan, Ann Arbor, MI, USA