Lithio derivatives, conversion

The reaction of lithio derivatives with appropriate electrophiles has been utilized in the preparation of alkyl, aryl, acyl and carboxylic acid derivatives. Representative examples of these conversions are given in Scheme 79. Noteworthy is the two-step method of alkylation involving reaction with trialkylborane followed by treatment with iodine (78JOC4684). 

This can be achieved by an indirect method. The lithio derivative is first reacted with a borate ester. Sequential acid hydrolysis and oxidation yields the corresponding hydroxy derivative. This procedure is illustrated by the conversion of 2-lithiobenzo[6]thiophene to 2-hydroxybenzo[6]thiophene, which exists predominantly in the 2(3//)-one tautomeric form (200) <70JCS(C)1926). 

The syntheses of 4-methoxycarbonyl- (60) and 4-formylbenzo[6]thiepin (61) were also achieved by a procedure involving conversion of the 1-lithio derivative of 46 to the corresponding bicyclobutanes by treatment with methyl chloroformate and ethyl... 

The lithio derivatives 63 are converted into deuteriopyrazines 64, and their yields can be equivalent to those of the hydrogen/lithium exchange (Scheme 15). As a result, the lithiation of chloropyrazines and pyrazinethiocarboxamide is optimized at —70 to —75°C, whereas that of methoxy- or acylamino-pyrazines at 0°C. Conversely,... 

R S(Q)CH, R2 — R AC(0)R2The conversion of sulfoxides (2) into thiol esters (5) is possible via the sulfoxide phosphines (3), which rearrange slowly at 0-20° or, more efficiently, in the presence of iodine, to phosphine oxides 4. These can be oxygenated via the a-lithio derivative to thiol esters 5. 

Azides are formed by the reaction of lithio derivatives with />-toliicncsulfonyl azide, and these in turn can be converted into the corresponding amino compounds by a variety of reductive procedures. Nitro compounds are available by a novel reversal of the general pattern of reaction with electrophiles. This approach requires the initial conversion of the lithio compound into an iodonium salt followed by reaction with nitrite ion. This is illustrated by the preparation of 3-nitrothiophene (Scheme 145). Other nucleophiles, such as thiocyanate ion which yields the 3-thiocyanate, can be employed. The preparative significance of these reactions is again that products not accessible by electrophilic substitution can be obtained. 

The stabilities of the acyl anion equivalent (30) and the lithio derivative (31) are enhanced by chelation between the two oxygens of the ketal group and the lithium cation. Scheme 5 shows a sequence for preparing ketones and aldehydes from (30), and Scheme 6 shows the conversion of (31) to a jS,y-unsaturated ketone. ... 

Similar halogenations have been done on 2-lithio-l-phenylsulfonylindole[2], 2-Lithio-l-phenylsulfonylindole is readily converted to the 2-(trimethylsilyl) derivative[2,3]. 2-Trialkylstannylindoles can also be prepared via 2-lithio-indoles[4,5], 2-Sulfonamido groups can be introduced by reaction of a 2-lithioindole with sulfur dioxide, followed by conversion of the sulfinic acid group to the sulfonyl chloride with A-chlorosuccinimide[6]. 

Bromodesilylation T-methoxy-l-indanones. Cyclization contrary to the normal para-selectivity of anisole derivatives can be effected by temporary use of an ort/jo-trimethylsilyl group introduced by directed orf/io-metallation (11,75). Thus the anisole derivative 1 undergoes bromodesilylation and hydrolysis to provide 2. This product undergoes cyclization to 3 in good yield on conversion to the lithio salt followed by bromine-lithium exchange (8,65-66). 

The lithiation of isophthalic acid can be achieved either at 2- or 4- position after conversion of the carboxylic acid groups to oxazole derivatives or N,N -butylamide derivatives respectively. Conversion to N-methyl amide derivative leads to the precipitation of the N-lithio salt on treatment with BuLi which fails to lithiate further. The N-lithio salt of the N-butylamide, however, remains in solution under the experimental conditions. It may be noted that the two lithiation reactions furnish two different carboxydihydroisocoumarins. The 5-carboxy dihydroisocoumarin can be converted to erythrocentaurine, which is naturally occurring... 

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