Grignard reagents direct synthesis

Pyridine undergoes 2- and 4-alkylation with Grignard reagents, depending on whether free metal is present (19). Free metal gives mixtures or exclusive 4-alkylation. Substituent-directed metaHation (eq. 5) has become an important approach to the synthesis of disubstituted pyridines (12). For example, 2- uoro-pyridine [372-48-5] reacts with butyUithium and acetaldehyde to give a 93% yield of alcohol [79527-61-1]. 

This phenol synthesis complements the analogous reaction (see below) from arylthallium ditrifluoroacetates (147). Although yields are only moderate, the procedure represents a viable conversion of aryl Grignard reagents to phenols. It is a practical method, however, only when the diarylthallium trifluoroacetate precursor is formed via the Grignard route the alternative synthesis via symmetrization of arylthallium ditrifluoroacetates is obviously circuitous, since the latter compounds may be converted directly to phenols. 

There is a short cut in the synthesis. The cyano-amlne (13), available from aldehyde (12), reacts with a Grignard reagent with loss of cyanide to give (9) directly. 

Yasuda S, Yorimitsu H, Oshima K (2008) Synthesis of aryliron complexes by palladium-catalyzed transmetalation between [CpFe(CO)2l] and aryl Grignard reagents and their chemistry directed toward organic synthesis. Organometallics 27 4025 027 Jonas K, Schieferstein L (1979) Simple route to Li- or Zn-metalated r -cyclopentadien-yliron-olefin complexes. Angew Chem Int Ed Engl 18 549-550... 

The alkylation of 15 (path b, Scheme 15)40 has been performed according to conventional procedures using lithium or Grignard reagents. The preliminary isolation of 15 is not essential thus, the synthesis of the zirconium alkyl or aryl derivatives can be carried out in situ directly from 3 (path a, Scheme 15). The h NMR spectra of 71-74 all imply C2V symmetry, as revealed by the CH2 (one pair of doublets), Bu (two singlets), and MeO (one singlet) patterns. All the alkyl derivatives 71-73 are thermally stable up to 80°C in CgDg. The aryl derivative... 

Polymer films may also be synthesized by direct chemical routesT 101. These chemical synthesis routes generally involve some form of electrophilic substitution using Grignard reagents or other modified precursors. The purity and electrical properties of the films produced from the chemical route are generally poorer than... 

Sequential cross-coupling can be used also for synthesis of 1,1-disubstituted alkenes from 2,3-dibromopropene (Aldrich). The allylic halogen couples directly with a Grignard reagent vinylic coupling is slower and requires a catalyst (equation I). 

Chiral butenolides are valuable synthons towards y-butyrolactone natural products [37] and have also been successfully applied to the synthesis of paraconic acids. The lactone 91, readily available from the hydroxyamide (rac)-90 by enzymatic resolution [38] followed by iodolactonization, proved to be an especially versatile key intermediate. Copper(I)-catalyzed cross coupling reactions with Grignard reagents allowed the direct introduction of alkyl side chains, as depicted in 92a and 92b (Scheme 13) [39, 40]. Further... 

The direct coupling of Grignard reagents with carboxylic acids Is not generally useful for ketone synthesis because of the accompanying formation of tertiary alcohols. An exception is the recently-published method using a nickel catalyst. In order to accomplish such a chemoselective ketone... 

The direct electrochemical synthesis (Scheme 2) of the addncts of organomagnesinm halides with 2,2 -bipyridine (6) and salts of organodihalogenomagnesinm(II) anions (7) was reported by Hayes and coworkers . Adducts of different stoichiometry and 7 were obtained in the electrochemical oxidation of magnesium in ACN solutions containing organic halides RX (8), a.ro-dihalides XR X (9) and 8 with ammonium salts R NX, respectively. All new products showed none of the typical reactions of Grignard reagents. 

For example, 2-bromoquinuclidine (80) does not form Grignard reagents and 2-aminoquinuclidine is so unstable that on hydrolysis of its urethans (81) under mild conditions ammonia is lost and polymers of dehydroquinuclidine are formed. The synthesis of 2-bromoquinuclidine (80) was achieved by the Borodin reaction,90 and the urethans (81) were obtained from quinuclidine-2-carboxhydrazide (82) by the Curtius reactions.142 The Curtius reaction with quinucli-dine-4-carboxylic acid derivatives gave 4-aminoquinuclidine (83).143 This compound (83) was also synthesized directly from quinuclidine-4-carboxylic acid by the Schmidt reaction. However, the first method is better, in spite of having more steps. 

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