Reductions lithium naphthalenide

Scheme 6 Dianionic cyclization of enediynes promoted by double lithium naphthalenide reduction.

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. 

Lithium halides (bromide or Iodide) may well modify the Lewis character of the zinc atom, probably via a zincate species [53], and prevent the efficient coordination of the zinc atom to the double bond, coordination which is required for the carbocyclization. Thus, in the Rieke method, it is essential to wash the active zinc thoroughly since the lithium naphthalenide reduction of zinc bromide also generates lithium bromide, which is detrimental to the success of the reaction. Indeed, the insertion of Rieke s zinc in the presence of LiBr leads to the linear organozinc iodide but not to the cyclic product [52]. 

It should be noted that this reported chemistry was performed with Rieke magnesium prepared by the MgCl2—KI—K—THF system. Rieke magnesium prepared by the safer lithium naphthalenide reduction approach should be expected to give the same or even improved results compared with what is reported here. 

Method 3 Active Zinc Prepared from the Stoichiometric Lithium Naphthalenide Reduction of Zinc Chloride... 

When (1) is treated with a fluoride source, a mild alkenation reagent is produced (eq 3). The efficient transformation of eno-hzable ketones and aldehydes under these conditions, as opposed to the lithium naphthalenide reduction process, aptly demonstrates this fact. 

A 17-steroidal ketone was deprotonated by LDA to protect it from reduction during a lithium naphthalenide cleavage of a benzyl ether. ... 

R R M were prepared by reduction of the dibromides R R MBr2 with lithium naphthalenide (method A), by thermolysis of a disilene (method B), and the ligand exchange of divalent group 14 element species (method C). In all cases except for the synthesis of Tip2PbS4, exclusively tetrasulfides R R MS4... 

For example, precursor (S)-57 may be prepared by reaction of R)-56 with methyllithium or by reduction of (S)-56 with lithium naphthalenide and subsequent methylation with iodomethane, making the overall transformation of the diastereomeric mixture 56 nearly quantitatively (Scheme 6) [87]. 

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... 

Attempts to form cyclotrigermanes (and, subsequently, digermenes see Section II.B.l) from the reductive cyclization of diaryldichlorogermanes and lithium naphthalenide (LiNp) with particularly bulky substituents on the aryl groups (i.e., isopropyl) led, instead, directly to the tetraaryldiger-menes by reductive coupling. 

Whitlock et al.14 discovered a reductive cyclization of enediynes promoted by lithium naphthalenide that provides substituted fulvenes and suggested a dianionic mechanism (Scheme 6). However, even now it is still unclear whether the enediyne dianion is indeed the cyclizing species or whether the initially formed acyclic radical-anion cyclizes first to give a fulvene radical-anion which is further reduced by lithium to give the cyclic dianion. 

Aromaticity of the products is only one of the factors accounting for the efficiency of these cyclizations as evidenced by the discovery of a dianionic synthesis of nonaromatic 5-membered heterocycles by Tamao and coworkers who found that reduction of bis(phenylethynyl)dialkylsilanes with lithium naphthalenide resulted in formation of a cyclized product by endo-endo cyclization15 (Scheme 7). 

Highly reactive calcium can be readily prepared by the reduction of calcium halides in tetrahydrofuran solution with preformed lithium biphenylide under an argon atmosphere at room temperature.5 This colored calcium species seems to be reasonably soluble in THF. However, the reactive calcium complex prepared from preformed lithium naphthalenide was insoluble in THF solution and precipitated out of solution to give a highly reactive black solid. The exact nature of this black calcium complex has not been determined. Acid hydrolysis of the black material releases naphthalene as well as THF. Accordingly, the most likely structure of the black material is a Ca-naphthalene-THF complex similar in nature to the soluble magnesium-anthracene complex recently reported.6... 

FIGURE 17a. Alternative routes for vinylogous birch reductive cleavage of cinnamyl ether promoted by lithium naphthalenide. Reprinted with permission from Reference 22. Copyright 1996 American Chemical Society... 

The synthesis of oxygen- and nitrogen-containing heterocyclic compounds by anionic cyclization of unsaturated organolithium compounds has been reviewed recently. " Broka and Shen reported the first intramolecular reaction of an unstabilized a-amino-organolithium compound using reductive lithiation of an A,5-acetal derived from a homoaUylic secondary amine (Scheme 21). Just one example was reported treatment with lithium naphthalenide gave the pyrrolidine product, predominantly as the cis isomer. 

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. 

Finely divided cobalt particles can be prepared by reduction of cobalt(ll) chloride by lithium naphthalenide in glyme. 

Strained cyclotrisilane derivatives, which are silicon analogues of cyclopropane, are prepared by the reductive coupling of overcrowded dichlorodiarylsilanes using lithium naphthalenide (Scheme 14.9). 

A fascinating feature of the chemistry of boron-phosphorus heterocycles is the existence of stable singlet biradicals, e.g. fBuBP Pr2)2 (for a discussion of the electronic structure, see Section 5.4.2.2). The synthesis of this four-membered ring is illustrated in Scheme 5.2. Related derivatives of the type (RBPR 2)2 are also prepared by a salt-elimination reaction of the appropriate lithium phosphide with a 1,2-dichlorodiborane or, in the case of the perphenylated derivative (PhBPPh2)2, by reduction of the cyclic dimer [Ph(Cl)BPPh2]2 with lithium naphthalenide (Scheme 9.11). ... 

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... 

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