Cuprates, methyl, reaction with

Formation of the very unstable dehydroalanine derivatives A p-dimethylaminophe-nyl- and Af-p-nitrophenyhnethylenedehydroalanine methyl ester could only be verified by -NMR. Because of Michael-type reactions with cuprates, the iV-arylmethylenedehy-droalanine methyl esters have been applied as building blocks in the synthesis of amino acids.[18]... 

Sn2 Reactions with epoxides and aziridines are also synthetically useful. An example of epoxide cleavage with an organocopper reagent with sp carbon moieties is the enantioselective synthesis of (3S, 4S)-4-methyl-3-heptanol (53), an elm bark beetle (Scolytus multistriatus) pheromone [42]. The chiral epoxy oxazolidine 51 [43], prepared from (R)-phenylglycinol, reacted with a propylmagnesium bromide-derived cuprate at —70 °C to afford the oxazolidine 52 in 74% yield (Scheme 9.12). Compound 52 was converted into the target molecular 53 by conventional procedures. 

Ss2 reaction with a,fi-epoxy ketones.6 The enolate 1 of 2,3-epoxycyclohexanone reacts with methyllithium to give, after acidic work-up, 2-methy -2-cyclohexenone (3), the product of SN2 addition. Reaction of 1 with lithium dimethyl cuprate on the other hand results in 6-methyl-2-cyclohexcnonc (2), the product of Sv2 addition. 

Leland and Kotick(87) extended their work to include B/C cis and B/C trans series (82) with antagonist N-substituents (CPM and CBM) in place of methyl and with 8-alkyl substituents. The latter substituents were inserted by reaction of intermediates 87 and 88 with lithium methyl cuprate. Lithium ethyl cuprate gave little of the desired product, and it was found more convenient to proceed to 8-ethyl derivatives by hydrogenation of the more amenable 8-vinyl intermediate. Alkyl functions were assigned the diequatorial conformation by reference to studies on 8-alkylmorphinan-6-ones.<88)... 

Related a,p-Unsaturated Esters. Similar a,p-unsaturated esters bearing a heterocyclic chiral auxiliary of a-amino acid origin at the p-position are known and have been utilized in asymmetric synthesis. Effective asymmetric conjugate additions of cuprates to (2), (3), and (5)J epoxidations of (3), and dipolar cycloadditions of (2) have been reported. Although oxazoli-dine (4) is only obtained as an 86 14 equilibrating mixture of stereoisomers, reactions with the lithium (Z)-enolate of methyl N-benzylideneglycinate (see Ethyl N-Benzylideneglycinate) are exclusively diastereoselective. 

Whereas these and other reports did not indicate the possibility of 1,4-cuprate additions to activated dienes, Yamamoto and co workers" showed in their seminal contributions that this is indeed feasible while the reaction of methyl sorbate with the Gilman cuprate M-Bu2CuLi provided exclusively the 1,6-addition product, the reagent formed from butylcopper and the Lewis acid boron trifluoride led to the 1.4-adduct as the major product (equation 15). The synthetically veiy useful organocopper compounds RCu have been named Yamamoto reagents. In certain cases, the regioselectiv-... 

For compounds in which the -carbon of the enolate is sterically hindered, this problem can normally be eliminated by the use of diethyl ether as the solvent. In several cases a switch from exclusive O-acylation in tetrahydrofuran to complete C-acylation in ether has been observed, and the conversion of 7 into 8 provides a typical illustration. When 3-methyl-2-cyclohexen-1-one 9 is converted into 10 by the addition of lithium dimethyl cuprate followed by in situ reaction with methyl cyanoformate, however, enol carbonate 11 accounts for 6% of the products. This can be avoided if the intermediate enolate is trapped as the enol trimethylsilyl ether and the enolate reliberated by treatment with butyllithium (note that the traditional reagent, methyllithium, Is Ineffective in ether as a solvem), but the overall yield is reduced. 

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