Grignard reagents derivatives

The synthesis involves the nickel-catalyzed coupling of the mono-Grignard reagent derived from 3-alkyl-2,5-diiodothiophene (82,83). Also in that year, transition-metal hahdes, ie, FeCl, MoCl, and RuCl, were used for the chemical oxidative polymerization of 3-substituted thiophenes (84). Substantial decreases in conductivity were noted when branched side chains were present in the polymer stmcture (85). 

Craig s synthesis of nicotine (V to VII, p. 42) proceeds via nomicotine. Nicotinic acid nitrile reacts with the Grignard reagent derived from ethyl y-bromopropyl ether to give 3-pyridyl-y-ethoxypropyl ketone (V). This yields an oily oxime (VI) reducible to a-(3-pyridyl)-a-amino-8-ethoxy-w-butane (VII), which with 48 per cent, hydrobromic acid at 130-3° gives womicotine, and this on methylation yields dZ-nicotine. 

The related compounds bis(2-mothyl-3-indolyl)glyoxal (263) and bis(3-methyl-l-indolyl)glyoxai (264) - have been prepared by the action of oxalyl chloride on the Grignard reagents derived from 2-methylindole and 3-methylindole, respectively, Eis(l-methyl-3-indolyl)-glyoxal (265) was prepared by the action of oxalyl chloride on 1-methyIindole in ether. 

A number of diindolylmethane derivatives including 336, 338, 339, 340, and 341 have been obtained by the action of the appropriate ketones, under fairly vigorous conditions, on the Grignard reagents derived from indole or 2-methylindole. ... 

Ingraffia studied the oxidation of the Grignard reagents derived from indole, skatole, and 2-methylindole with hydrogen peroxide and... 

Johnson s classic synthesis of progesterone (1) commences with the reaction of 2-methacrolein (22) with the Grignard reagent derived from l-bromo-3-pentyne to give ally lie alcohol 20 (see Scheme 3a). It is inconsequential that 20 is produced in racemic form because treatment of 20 with triethyl orthoacetate and a catalytic amount of propionic acid at 138 °C furnishes 18 in an overall yield of 55 % through a process that sacrifices the stereogenic center created in the carbonyl addition reaction. In the presence of propionic acid, allylic alcohol 20 and triethyl orthoacetate combine to give... 

Trialkylsilyl groups have a modest stabilizing effect on adjacent carbanions (see Part A, Section 3.4.2). Reaction of the carbanions with carbonyl compounds gives (3-hydroxyalkylsilanes. (3-Hydroxyalkylsilanes are converted to alkenes by either acid or base.270 These eliminations provide the basis for a synthesis of alkenes. The reaction is sometimes called the Peterson reaction.211 For example, the Grignard reagent derived from chloromethyltrimethylsilane adds to an aldehyde or ketone and the intermediate can be converted to a terminal alkene by acid or base.272... 

Another method of synthesis was also used. This involved the action of chloroacetaldehyde on the Grignard reagent derived from acetylene in order to obtain the meso divinylacetylene dichlorohydrin, CH2CI—CHOH—C=C—CHOH—CH C1, from which one passed to the corresponding hexynetetrol, CH2OH—CHOH—C=C—CHOH— CHjOH. This, in turn, was reduced to the hexenetetrol, CHjOH— CHOH—CH=CH—CHOH—CH2OH, by means of Bourguel s catalyst,8 a dispersion of colloidal palladium on starch. When the hexenetetrol was hydroxylated by the use of silver chlorate and osmic acid, two hexitols, dulcitol and allitol, were obtained. 

The desired intermediates, a pentadienol or a pentenetriol were unknown at the time, but it occurred to me that their synthesis might be accomplished by the partial reduction of a pentenynol or a pentynetriol, the latter being obtained from the reaction of one molecule of acrolein or acrolein dichloride with the Grignard reagent derived from acetylene. The reactions which have been carried out in accordance with this scheme are shown in the accompanying flow sheet. 

Kondo employed the Kumada coupling using the Grignard reagents derived from 2- and 3-iodo-l-(phenylsulfonyl)indole to prepare the corresponding phenyl derivatives in 50% yield [92], Widdowson expanded the scope of the Kumada coupling and provided some insight into the mechanism [93],... 

The dihydrooxazol-mediated biaryl coupling of nonracemic 11 with the Grignard reagent derived from l-bromo-2,3,4-trimethoxy-6-methylbenzene yielded (via intermediates of type 12) the two diastereomeric coupling products 13 and 14 in a 6 1 ratio. In this case the relative configuration around the biphenyl axis had to be determined (see p 478)122. 

The Grignard reagent derived from 10-bromo-l-methyl-10,ll-dihyarodibenzo-[6,/]azepine has been used to synthesize the 10-carboxylic acid (78MI51602). 

The Grignard reagents, once they are formed, react normally. Some examples are given in Scheme 184 (81S585). Grignard reagents derived from benzo[6]thiophenes also exhibit normal reactivity (70AHC(l 1)177). 

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