Alkylation with a Grignard reagent

Cuprous iodide catalyzes the reaction of various alkyl chlorides, bromides, and iodides in hexamethylphosphoric triamide (HMPT), to give the complexed product RaSnXj, which can then be further alkylated with a Grignard reagent, or can be hydrolyzed to the oxide and converted into various other compounds, R2SnY2 (43). This promises to be a useful laboratory method, e.g.,... 

The same nitrone 241 was employed in a stereoselective alkylation with a Grignard reagent by Petrini et al. <1995JOC5706> for another synthesis of lentiginosine. 

The use of prochiral secondary silanes in the asymmetric hydrosilation can give an optically pure sUylether, which can be alkylated with a Grignard reagent with retention of the... 

Acylated glycosyl thiocyanates are made by treatment of acylated glycopyranosyl halides with potassium thiocyanate.30 Reaction at —40° with a Grignard reagent affords alkyl or aryl 1-thioglycosides.54... 

In addition to magnesium, there is an extensive chemistry of organoberyllium compounds. The alkyl compounds are obtained most conveniently by the reaction of beryllium chloride with a Grignard reagent. 

Alkyl tin compounds can be prepared by the reaction of SnCl4 with a Grignard reagent,... 

The morpholin-4-yl substituent in 7-position behaves similarly to the ethoxy group. Compound 481 is easily prepared by double addition of benzotriazole to acrolein followed by elimination of one of the benzotriazolyl moieties induced by treatment with NaH. Lithiation of derivative 481 followed by addition to a Schiff base results in formation of diarylpyrrole 476. Lithiated product 481 is alkylated exclusively at the carbon a, in relation to the benzotriazolyl substituent, giving intermediate 482. Subsequent treatment with a Grignard reagent leads to enamine 483 (Scheme 79) <1995TL343>. 

The electrochemical oxidation of l-MeO-7-alkyl-CHT in MeOH yields 2-alkyltropones, while the thermal rearrangement of 3-MeO-7-alkyl-CHT to l-MeO-4-alkyl-CHT followed by its anodic oxidation in MeOH affords 4-alkyltropones (equation 21). l-MeO-7-alkyl-CHT is prepared by the regioselective alkylation of 7,7-diMeO-CHT with a Grignard reagent and Cul, while 3-MeO-7-alkyl-CHT is also regioselectively prepared by alkylation of 7,7-diMeO-CHT with an alkyl lithium. 

In the first systematic study on nucleophilic substitutions of chiral halides by Group IV metal anions, Jensen and Davis showed that (S )-2-bromobutane is converted to the (R)-2-triphenylmetal product with predominant inversion at the carbon center (Table 5)37. Replacement of the phenyl substituents by alkyl groups was possible through sequential brominolysis and reaction of the derived stannyl bromides with a Grignard reagent (equation 16). Subsequently, Pereyre and coworkers employed the foregoing Grignard sequence to prepare several trialkyl(s-butyl)stannanes (equation 17)38. They also developed an alternative synthesis of more hindered trialkyl derivatives (equation 18). 

In the course of a study on creation of a library of a great number of hetaryl ketones and related derivatives, Szewczyk et al. <2001AGE216> elaborated a ruthenium-catalyzed transformation of heterocycles with activated C-H bond by reaction with olefins and carbon monoxide. Thus, 253 gave 254, albeit in very poor yield. Synthetically, the more straightforward iron-catalyzed transformation was described by Fiirstner et al. <2002JA13856>. These authors reacted 255 with a Grignard reagent in the presence of Fe(acac)3 to afford the 7-alkyl-substituted derivative 256 in reasonable yield (acac = acetylacetonate). 

A partial mechanism forthe conversion of an alkyl halide to a nitrile, which reacts to form a ketone with a Grignard reagent. 

In 1990, Hahn and Tompkins reported an interesting multi-carbon homologation of alkyl halides by the reaction of magnesium carbenoid with a Grignard reagent (Scheme 2) . 

Alkyl and aryl complexes of the type [AuRL] may also be prepared by reaction of a halide complex with a Grignard reagent. Thus have been... 

The ketocarbene is formed from 3-phenylpropanoyl chloride (dihydrocinnamic acid chloride) and diazomethane ring substituted dihydrocinnamic acids provide a route to substituted azulenes. Alternatively the keto group in (25) may be treated with a Grignard reagent for the introduction of alkyl substituents into the five-membered ring. 

Alkylpyridines.3 Highly selective alkylation of pyridine at C4 is possible by quatemization with this triflate followed by reaction with a Grignard reagent. Substitution occurs with almost complete regiospecificity ( > 99%) to give 4-alkyl-l, 4-dihydropyridines, which are oxidized by oxygen to 4-substituted pyridines (equation 1). 

Further, Taylor and co-workers carried out reactions to attach a suitable side chain at nitrogen, which subsequently could be cyclized to give aza analogues of ft-lactam antibiotics. Thus, the readily available inner salt 1,1-disubsti-tuted-3-oxo-l,2-diazetidinium tosylate 209 was selectively reduced at the side chain attached to N-l of 210 by sodium borohydride, or was alkylated selectively at the side chain by the reaction of 210 with a Grignard reagent (Scheme 30) <1984JOC4415>. 

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