Reductive metalations, lithium naphthalenide

Intermediates 663 can be prepared by tin-lithium transmetallation with w-BuLi from a-stannylated vinyl sulfides974. Starting from l,l-bis(arylsulfanyl)ethenes, a reductive metallation with lithium naphthalenide at —70°C is a very efficient approach to lithiated vinyl sulfides975,976. Other methods involved bromine-lithium exchange977 or addition of methyl or phenyllithium to thioketenes978. A convenient method for the preparation of l-(methylsulfanyl) and l-(phenylsulfanyl) vinyllithiums was the treatment of 2-methoxyethyl sulfides with 2 equiv of w-BuLi-TMEDA at — 30 °C979. 

In 1973, the direct potassium metal reduction of zinc salts was reported.3 This active zinc powder reacted with alkyl and aryl bromides to form the alkyl- and arylzinc bromides under mild conditions.4 The reduction of anhydrous zinc salts by alkali metals can be facilitated through the use of electron carriers. Lithium and sodium naphthalenide reduce zinc salts to give highly reactive metal powders under milder and safer conditions. Graphite5 and liquid ammonia6 have also been employed as electron carriers in producing zinc powders. A highly dispersed reactive zinc powder was formed from the sodium metal reduction of zinc salts on titanium dioxide.7... 

When there is no programmed radical cyclization reaction as discussed in the preceding section, the anomeric radical generated under reductive metallation conditions will obviously be reduced to an organometallic. This is no longer radical chemistry but the radical initiation will impose the stereoselectivity of the anionic process that follows if kinetic conditions are maintained. This situation is observed in the reductive lithiation with lithium naphthalenide (LN) of derivatives 10 where X can be Cl, SPh, or SOjPh (Fig. 13), a process first reported on cyclic a-alkoxyphenyl sulfides. ... 

The effect of surface has also been demonstrated in the reduction of anti-3-chloro-exo-tricyclo[3.2.1.0 " ]octane (100). When the reduction is carried out by lithiation in ether followed by deuterolysis the ratio of syn product 102 to anti product 101 was about 2 1 whereas reduction under homogeneous conditions, lithium naphthalenide followed by deuterolysis, resulted in a 30 1 ratio. Again, there is greater retention on the metal surface. The syn g radical was shown to be the thermodynamically more stable (Table 13). 

A number of substituted cyelopropanes have been prepared by reductive lithiation of various l,l-bis(phenylsulfanyl)cyclopropanes followed by reactions of the resulting a-phenylsulfanyl-cyclopropyl anions with selected electrophiles. Metalation can be carried out by several methods, cf 1, ° but reduction with two equivalents of lithium naphthalenide in tetrahyd-rofuran at — 70°C is the most efficient. The product yields are generally satisfactory with carbon dioxide and benzaldehyde as trapping agents. Thus, when 2-methyl-1,1-bis(phenylsul-fanyl)cyclopropane was used as starting material, 2-methyl-l -(phenylsulfanyl)cyclopropanecar-boxylic acid (2 b) and (2-methyl-l-phenylsulfanylcyclopropyl)(phenyl)methanol (3 c) were obtained in 86 and 76% yield, respectively. ... 

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]. 

Use of Lithium Naphthalenide. Lithium arene radical anion complexes are mild and highly effective reagents for the reductive desulfonylation process of functionalized sulfones. These reagents have only rarely been used with vinylic and allylic sulfones. In addition to high yields and their operational simplicity, metal arene radical anion complexes demonstrate high chemoselectivity (Eq. 67).123... 

The reductive cleavage of allylic tosylmethyl ethers with lithium naphthalenide in THF is used to prepare metalated allylic ethers that undergo [2,3] Wittig rearrangements in situ (Eq. 72).128... 

From the experimental point of view, reductive desulfonylations with alkali metal arene radical anion complexes require a large excess of the radical anion, very short reaction times at low temperatures, and must be run under an inert atmosphere. Sodium or lithium naphthalenides in tetrahydrofuran at —78° or lower temperatures are typical reaction conditions. Tetrahydrofuran solutions of lithium naphthalenide are dark green. This color is lost when the substrate is added and restored once the reaction is finished. Upon completion, the excess reagent is quenched with a saturated aqueous solution of ammonium chloride or low molecular alcohols such as methanol or ethanol. 

Dianion Generation. Lithium naphthalenide efficiently de-protonates alkynyloxy " and carboxylate anions (eq 5). In addition, the previously mentioned phenomenon of reductive metalation has been exploited to access dianions fromhalohydrins, -halo carboxylic acids, and -halo carboxamides, and even trianions from -dihalo alcohols. A major pathway for the polyanionic species is -elimination (eq 6) when such processes can be avoided, the polyanions react according to Hauser s rule (eq... 

A far superior method of preparing the highly reactive zinc is to use lithium metal as the reducing agent along with an electron carrier such as naphthalene (Method 2). This approach is considerably safer as there is no rapid burst of heat. The dark green lithium naphthalenide also serves as an indicator, signaling when the reduction is over. 

A new, highly reactive copper species made from the reduction of copper(I) complexes with two equivalents of preformed lithium naphthalenide leads to a reagent that behaves chemically as a formal copper anion solution [20]. Lithium naphthalenide provides a suitable reducing agent for a variety of metals and offers unique advantages over other techniques used in metal activation, such... 

Rieke has demonstrated that the generation of active metals can be readily achieved by in situ reduction of the corresponding metallic salts with lithium naphthalenide [5]. Many copper(i) salts can be reduced under such conditions and the choice of the optimum reaction conditions is essential for the success of the insertion reaction [6]. The presence of phosphine ligands leads to highly active copper(O)-powder. The use of BUjP Cul as copper(i) salt is especially well suited and allows the subsequent opening of epoxides (Scheme 9.1). 

Allylmetallic reagents The ally] anions obtained by reductive metallation of ally I phenyl sulfides with lithium l-(dimethy amino)naphthalenide (LDMAN, 10, 244) react with a, 3-enals to give mixtures of 1,2-adducts. The regioselectivity can be controlled by the metal counterion. Thus the allyllithium or the allyltitanium compound obtained from either 1 or 2 reacts with crotonaldehyde at the secondary terminus of the allylic system to give mainly the adduct 3. In contrast the allylcerium compound reacts at the primary terminus to form 4 as the major adduct. 

Reaction of dichloro(pentamethylcyclopentadienyl)silane with lithium, sodium or potassium naphthalenide gives a mixture of elemental silicon, the corresponding alkali metal pentamethylcyclopentadienide and decamethylsilicocene (82) (equation 64)181. Compound 82 is formed as the only product in the reduction of dibromo-bis(pentamethylcyclopentadienyl)silane with potassium anthracenide (equation 65)182. 

Reduction of [V(bipy)3]l2 with the metals Mg or Zn yields the complex [V(bipy)3], which will undergo ftulher reduction by lithium aluminum hydride to Li[V(bipy)3] 4THF, which formally contains V". Similarly, reduction of [V(phen)3] with dUithium naphthalenide or dihthium benzophenone in THF yields [V(phen)3]l2. Further reduction with dilithium benzophenone gives the V complex Li[V(phen)3] 3.5THF. The terpyridyl complex [V(terpy)2] can be obtained as black crystals by reduction of DMF solutions of [V(terpy)2]l2 with Mg or LiAlH. Such low oxidation state complexes are highly air sensitive and decompose if heated to 100 - 200 °C in a vacuum. In these systems, the ligands may have an anion radical character. ... 

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