Lithium 1-methyl 2- cuprate

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)... 

The reaction of lithium methyl cuprate reagents with 2,3- and 3,4-anhydro-hexopyranosides carrying methyl groups on either oxiran carbon has been studied while the expected trans C-methyl substitution occurred in a majority of cases, e.g., (18)+(19), elimination to unsaturated compounds also occurred, e.g., (20)+(21)+(22), (23)- (24), and (25)- (26). ... 

Although ethereal solutions of methyl lithium may be prepared by the reaction of lithium wire with either methyl iodide or methyl bromide in ether solution, the molar equivalent of lithium iodide or lithium bromide formed in these reactions remains in solution and forms, in part, a complex with the methyllithium. Certain of the ethereal solutions of methyl 1ithium currently marketed by several suppliers including Alfa Products, Morton/Thiokol, Inc., Aldrich Chemical Company, and Lithium Corporation of America, Inc., have been prepared from methyl bromide and contain a full molar equivalent of lithium bromide. In several applications such as the use of methyllithium to prepare lithium dimethyl cuprate or the use of methyllithium in 1,2-dimethyoxyethane to prepare lithium enolates from enol acetates or triraethyl silyl enol ethers, the presence of this lithium salt interferes with the titration and use of methyllithium. There is also evidence which indicates that the stereochemistry observed during addition of methyllithium to carbonyl compounds may be influenced significantly by the presence of a lithium salt in the reaction solution. For these reasons it is often desirable to have ethereal solutions... 

Lithium, methyl, 55,7, 10 Lithium, phenyl-, 55,11 Lithium phenylthio(alkyl)cuprates, 55,122 LITHIUM, phenyltluo(fe/f-butyl)cuprate [Lithium, phenylthio( 1,1 -dimethyl-ethyl)cupiate, 55,122 Lithium, 1-propenyl-, 55, 111 LITHIUM, ( >l-propenyl-, 55, 103 Lithium thiophenoxide [Ben7enethiol, lithium salt], 55, 122... 

A multi-step reaction sequence was then realized to prepare the precursor (178) for the pivotal macrocyclization reaction. Alternate stepwise chain elongations were achieved according to Schemes 28 and 29. Reaction of the tosylate prepared from the alcohol 162 with lithium acetylide afforded the alkyne 174 (Scheme 28). Following the introduction of a tosylate at the upper branch, a one-carbon chain elongation of the terminal alkyne afforded the methyl alkynoate 175. A methyl cuprate 1,4-addition was used to construct the tri-substituted C double bond stereoselectively. For this purpose, the alkynoate 175 was initially transformed into the Z-configured a,/ -unsat-... 

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. 

H. Yamamoto, H. Sasaki, and S. Inokawa, Reaction of lithium dimethyl cuprate with methyl 2,3-anhydro-5-deoxy-a-D-ribofuranoside. A new, convenient route for the preparation of 2,5-dideoxy-2-C-methyl-D-arabinofuranose derivatives, Carbohydr. Res. 100 C44 (1982). 

One general method for acyl silane synthesis particularly successful for a-cyclopropyl examples (and even an a-cyclobutyl example) involves treatment of acid chlorides with lithium tetrakis(trimethylsilyl) aluminum or lithium methyl tris(trimethylsilyl) aluminium and cuprous cyanide (vide supra, Section III.A.3)77. For example, cyclopropyl acyl silane (23) was obtained in 89% yield by this process. Improved procedures use lithium t-butyldimethylsilyl cuprate78 and a dimethylphenylsilyl zinc cuprate species79,80 as reagents. 

A report of House, Respess and Whitesides (47) showed that the reaction of lithium dimethyl cuprate with the unsaturated ketone 135 gave exclusively the ketone J36 having the methyl trans to the t-butyl group. In this case where the double-bond is exocyclic, stereoelectronic effects allow equal attack from either face. Thus, the exclusive formation of 136 must be due to steric reasons only, the equatorial approach being favored. 

D. R. Hicks, R. Ambrose, and B. Fraser-Reid, Lithium dimethyl cuprate cleavage of diastereomeric 2,3-anhydro sugars a route to 2- and 3-C-methyl hex-2-enopyranosides,... 

The coupling reaction between lithium dimethyl cuprate and acyclic enol phosphates must be carried out between -47 and -98°C for stereoselective formation of g-methyl-a,g-unsaturated esters. 

Mori started with the early introduction of the chiral centre [298] in using (3-oxidation of pentanoic acid A by the yeast, Candida rugosa, IFO 0750 [299]. The obtained (R)-3-hydroxypentanoic acid B was transformed into C in a few conventional steps. The second building block was prepared from methyl 2-pentynoate D conjugate addition of lithium dimethyl cuprate yielded E, which was further converted into the frans-configured vinyl bromide F. Hydro-boration of C yielded G which upon Suzuki s palladium catalysed cross-coupling with F furnished 157 after treatment of the reaction product with hydrochloric acid followed by chromatographic purification. The synthesis of ent-157 used (S)-3-hydroxypentanoic acid. 

The alkyls and aryls may be obtained by interaction of copper(I) halides with lithium or Grignard reagents. The alkyls usually decompose readily but methyl copper, a bright yellow polymer insoluble in organic solvents, is reasonably stable it can be used in certain organic syntheses, but the use of lithium alkyl cuprates... 

Allenes are activated by a diphenylphosphine oxide substituent towards nucleophilic substitution at the j3-carbon atom. Lithium dimethyl-cuprate adds quickly to the 1,2-bond to give, on hydrolysis, the olefin in 16-84% yield, according to the nature of the substituents (76). Optimum conditions were not reported. The intermediate a-copper compound resulting from the addition can be dimerized or reacted with methyl iodide [Eq. (106)]. Similar reactions involving methyllithium are complicated. 

The preparation of a 7-substituted morphinan in high yield was first accomplished in 1980.(82) Thebaine (78) was reacted with lithium dimethyl-cuprate to yield (90%) 7/3-methyldihydrothebaine- > (79) together with 4% of the 7a-epimer. Previously, dihydrothebaine(83) and the enol acetate of dihydrocodeinone(84) had been shown to react with methyl Grignard reagents affording predominantly 5-methyldihydrothebainone with only a trace of the 7-methyl isomer.(85) The production of 79 gave entry into a new series of morphinans. 

In another synthesis the diol 155 was oxidized with silver carbonate on Celite to the lactone 156 convertible (lithium dimethyl cuprate, debenzylation, and dehydration) to ( )-eldanolide [( )-129]. Finally a synthesis of racemic eldanolide involved coupling of a C4 unit, 157, with 4-methyl-3-pentenal. In tetrahydrofuran at -78 C, the reaction occurred at the y-position to the metal atom (158) to yield 72% of the alcohol 159, which gave 98% ( )-129 with mercuric chloride. ... 

An improved method for the preparation of methyl 2-oxo-5-vinyl-cyclopen-tanecarboxylate (389) by treatment of dimethyl ( )-2-hexenedioate (390), with the cuprate made from vinyllithium and copper(I) cyanide (77-85%), led to a short synthesis of mitsugashiwalactone (391) (Scheme 34), another noriridoid isolated from Boschniaka rossica Borohydride reduction and dehydration gave methyl 5-vinyl-l-cyclopentenecarboxylate (392), and this could be cyclized by hydroboration and extended treatment with hydrogen peroxide—conditions for the highest yield in the cyclization seem to be with hydroboration in base— then a separate acid-catalyzed cyclization. The methyl group was added with lithium dimethyl cuprate. ... 

In a third synthesis of rose oxide (909) from the lactone 919, addition of propynyllithium, followed by borohydride reduction, gave the diol 920, to which the additional methyl group was added with lithium dimethyl cuprate. Hydrolysis and treatment with silver nitrate yielded the rose oxides (909). This same paper describes a related synthesis of the naturally occurring 2,2,6-trimethyl-6-vinylpyran (921) (Vol. 2, p. 167). 

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