Dilithio intermediates

Rearrangement to an open chain imine (165) provides an intermediate whose acidity toward lithiomethylthiazole (162) is rather pronounced. Proton abstraction by 162 gives the dilithio intermediate (166) and regenerates 2-methylthiazole for further reaction. During the final hydrolysis, 166 affords the dimer (167) that could be isolated by molecular distillation (433). A proof in favor of this mechanism is that when a large excess of butyllithium is added to (161) at -78°C and the solution is allowed to warm to room temperature, the deuterolysis affords only dideuterated thiazole (170), with no evidence of any dimeric product. Under these conditions almost complete dianion formation results (169), and the concentration of nonmetalated thiazole is nil. (Scheme 79). This dimerization bears some similitude with the formation of 2-methylthia-zolium anhydrobase dealt with in Chapter DC. Meyers could confirm the independence of the formation of the benzyl-type (172) and the aryl-type... 

Reaction of thiophene or of 2-alkylthiophenes with butyllithium in the presence of HMPT is suggested to lead to the generation of dilithio intermediates (12), which are then cleaved in the usual way (entry 2 in Table I) the use of HMPT is critical in bringing about ring cleavage. 3,4-Dilithio species (13) give conjugated diacetylenes as products (see entries 17 and 26). 

In the case of 4-piperidinosulfonylpyridine (469), higher amounts of LDA are detrimental, leading to dimetalation (e.g., I2 or PhCHO quenches led to mixtures of respective 3-substituted and 3,5-disubstituted products which favored the latter at longer metalation times). A 3,5-dilithio intermediate was ruled out by deuterium incorportion experiments. In fact, it appeared that the reaction of LDA and the electrophiles are slower than C-5 deprotonation of the monosubstituted product 470. Scheme 141 summarizes results of LDA metalation experiments on the piperidyl sulfonamide 469 leading to products 470 and 471, which support some of the previous facts (87JOC1133). 

Thieno-l,3-dithiolane-2-thione (62ACS105) was prepared by a convenient one-flask reaction in which 3,4-dibromothiophene was twice treated with BuLi followed by elemental sulfur at —78 °C to provide the dilithio intermediate. This sequence was followed by the addition of an excess of CS2 and 2N NaOH (equation 8). Alternatively, the dilithio intermediate could be protonated, and the resulting dithiole allowed to react with thiocar-bonyldiimidazole (81CC920). 

The central ring of both dibenzo[l,4]- dithiins and -oxathiins is cleaved on treatment with Li and a catalytic amount of 4,4"-di-rert-butylbiphenyl (DTBB) to afford thiols after reaction of the dilithio intermediate with electrophiles. In certain instances, the initial product can be cyclised to the dibenzo- dithiepine and -oxathiepine <02CL726>. The dilithio salt from thianthrene reacts sequentially with two different carbonyl compounds to give a l,2-di(hydroxyalkyl)benzene. When C02 is used as the second electrophile, a phthalan results <02TL7205>. 

Rearrangement to an open chain imine (165) provides an intermediate whose acidity toward lithiomethylthiazoie (162) is rather pronounced. Proton abstraction by 162 gives the dilithio intermediate (166) and regenerates 2-methyIthiazole for further reaction. During the final hydrolysis, 166 affords the dimer (167) that could be isolated by molecular distillation (433). A proof in favor of this mechanism is that when a large excess of butyllithium is added to (161) at and the solution is... 

A dibromomethylcycloalkanol rearranges in a similar fashion, except that a different dilithio intermediate is formed via halogen-metal exchange rather than deprotonation (Scheme 16). With unsym-metrical ketones, the more substituted group migrates. This selectivity has been applied to a synthesis of ( )-muscone (29 Scheme 17). Substituted polyhalomethyllithium species can be used in the prepara-... 

As mentioned in the introduction, very few examples to selenophene or tellurophene were reported this year. Metdlacycle transfer from zirconium metallacycles such as to the corresponding selenophenes can be accomplished in "one-pot" spthesis (Eq. 20) <94JAI880>. Treatment of the dilithio intermediate 109 with either red selenium or tellurium powder affords the corresponding 1-benzometalioles. The trimethylsilyl group is later removed with TBAF <94CPB1437>. 

In the presence of excess n-butyllithium, 1-methylpyrrole is dilithiated to give a mixture of both 2,4- and 2,5-substitution products (Scheme 117) <77JCS(Pi)887, 91TL4313). Inclusion of TMEDA in the lithiation reaction favors the 2,5-dilithiation, but not much synthetic application has been made of the dilithio intermediate. 

Apparent anomalies in reactivity have appeared to exist for a number of reactions. It is not generally known that under conventional EQ conditions, an electrophile can promote aromatic metalation during the quench step. It was stated in an early report [130] that the reaction of phenothiazine 31 with 2 equivalents of n-BuLi proceeds with formation of dilithio intermediate 33 via monoUthio amide 32 (Scheme 26.8). The fact that the regioselectivity of the reaction is dependent on the electrophile used was not properly analyzed by the authors whereas trapping experiments with RCOX=DME, PhCONMe, MeCO Li, PhCO Li, and CO give C(7j-acylation products 34, the reaction of RX = MeCOCl, Mel, and ethylene oxide provides lVjf70)-substitution products 35. 

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