Alkylations lithium naphthalenide

Beau and Sinay described a method which laid the groundwork for cyanohydrin acetonide alkylations [1]. Their strategy involved alkylation and reductive desulfonylation of glucopyranosyl sulfones 4. In this one-pot procedure, low temperature alkylation and subsequent reductive desulfonylation with lithium naphthalenide generated -C-glycosides with good selectivity >10 1 j3 a) and in moderate to good yield (Eq. 1). 

Alkenylsilanes can be prepared from aldehydes and ketones using lithio(chloromethyl)trimethylsilane. The adducts are subjected to a reductive elimination by lithium naphthalenide. This procedure is stereoselective for the E-isomer with both alkyl and aryl aldehydes.82... 

Preparation from activated Cb(O).1 An activated Cu, prepared by lithium naphthalenide reduction of CuIPBu3 (12,140), reacts with primary alkyl bromides at -50 to -78° to form alkylcopper reagents that undergo 1,4-addition to cyclo-hexenone in moderate to high yield. This conjugate addition is facilitated by ClSi(CH3)3 and a phosphine. 

The allylic alkylation products represent useful synthons, as exemplified by the reaction sequence outlined in Scheme 10.4. For example, reductive ozonolysis of the allylic alkylation product 15 afforded the y-lactone 16 as a single diastereoisomer. Sequential alkylation with methyl iodide, and reductive alkylation using lithium naphthalenide with allyl iodide furnished the ternary-quaternary substituted y-lactones 17a/17b in 72% overall yield, as a 10 1 mixture of diastereomers favoring 17a [18]. This method provides a versatile approach to the construction of a variety of a-quaternary-/9-ternary stereogenic centers. 

Lithium naphthalenide has been used for reductive lithiation of thioketals (8, 306 9, 284), but has the disadvantage that naphthalene is sometimes difficult to separate from final products of alkylation. In such cases, lithium I -(dimethylamino)-naphthalenide can be used advantageously since dimethylaminonaphlhalene is removed from reaction mixtures by extraction with dilute acid.1... 

A remarkable stereospecific dehydrative alkylation of (3-disulfones was reported by Falck et al. [406] under Mitsunobu conditions (triethyl phosphine, diethyl azodicarboxylate). The synthesis of a pheromone component of the lesser tea tortrix emphasizes some of the possibilities offered by coupling this reaction with further uses of the sulfone functionality. In the present case, monodesulfonylation with lithium naphthalenide (-78°C, 5 min), in situ alkylation (-78 to 23°C, 1 h), and Li-naphthalene cleavage of the second sulfonyl group (—78°C, 5 min) yielded in a one-pot procedure a THP ether which was converted into the sought after pheromone through direct acetylation. 

The corrinoid-mediated reduction of polyhaloethenes has been the subject of a recent study, which reports reaction via homolytic C-halogen bond fission. The elimination of a further halogen radical affords haloalkynes, which lead to acetylene itself.56 The electron transfer-induced reductive cleavage of alkyl phenyl ethers with lithium naphthalenide has been re-examined in a study which showed that it is possible to reverse regioselectivity of the cleavage (i.e. ArOR to ArH or ArOH) by introduction of a positive charge adjacent to the alkyl ether bond.57 A radical intermediate has been detected by ESR spectroscopy in the reduction of imines to amines with formic acid58 which infers reacts takes place via Lukasiewicz s mechanism.59... 

At this time the applicability of organozinc chemistry had been limited to those zinc reagents that could be prepared by insertion of zinc powder into the corresponding alkyl iodide.20 Further developments, notable the use of highly reactive zinc (Rieke zinc), obtained by the reduction of zinc halides with lithium naphthalenide, allowed the preparation of zinc reagents from otherwise unreactive organic substrates, such as aryl iodides and aryl bromides (Scheme 1.7).21... 

The first step in the reductive lithiation of alkyl phenyl sulfides (Screttas-Cohen process) consists of preparing the reducing reagent in stoichiometric amounts. Lithium naphthalenide, for example, is made from lithium and naphthalene. The sulfide is added drop wise to this reducing reagent. The mechanism of reduction corresponds step by step to the one outlined in Figure 17.44, except that the dissolved radical anion is the source of the electrons, as opposed... 

Alkyl halides (particularly bromides) undergo oxidative addition with activated copper powder, prepared from Cu(I) salts with lithium naphthalenide, to give alkylcopper species10. The alkyl halides may be functionalized with ester, nitrile and chloro functions ketone and epoxide functions may also be tolerated in some cases11. The resulting alkylcopper species have been shown to react efficiently with acid chlorides, enones (conjugate addition) and (less efficiently) with primary alkyl iodides and allylic and benzylic bromides (equations 5 and 6). If a suitable ring size can be made, intramolecular reactions with epoxides and ketones are realized. 

Reactions of metal organic compounds with alkyl halides, such as alkyl-lithium-alkylhalide reactions 2 .c,d,f,h,ii8 -d io) and reactions of Grignard compounds and sodium-naphthalenide D with alkylhalides,... 

A variation of this transformation reacts the acid with lithium naphthalenide in the presence of 1-chlorobutane. The product is the ketone. A related reaction treats the lithium carboxylate with hthium metal and the alkyl hahde, with sonica-tion, to give the ketone. Phenylboronic acid (p. 815) reacts with aryl carboxylic acids in the presence of a palladium catalyst and disuccinoyl carbonate to give a diaryl ketone. " ... 

Monoorganozinc halides (RZnX) can be synthesized by oxidative addition of organic halides to zinc metal. The oxidative addition rate is strongly affected by the reaction conditions (solvent, concentration) [16] and by activation of the zinc [15,17]. Zinc powder or zinc foil, which is activated by treatment with 1,2-dibromoethane and then with trimethylsilyl chloride, will oxidatively add alkyl iodides [18]. The reaction of alkyl bromides, on the other hand, requires more active zinc, which may be prepared by the reduction of zinc chloride with either lithium naphthalenide [19] or lithium metal under ultrasonic.irradiation [20, 21]. 

Beau and Sinay have developed an efficient synthesis of 2-deoxy-jS-glycosides based on anomeric phenylsulfone alkylation followed by in situ reductive lithiation with lithium naphthalenide (LN). The -C-glycoside product is established after protic quench of the intermediate axial alkyllithium (Scheme 12) [20]. 

Lithium methylsulfinylmethylide, 342 Lithium methyl(vinyl)cuprate, 342-343 Lithium naphthalenide, 415 Lithium organocuprates, 225 Lithium perchlorate, 103 Lithium phenylethynolate, 343 Lithium phenylthio(alkyl)cuprates, 344, 465... 

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