Grignard reagents, oxidative dimerization

The oxidative dimerization of the anion of methyl phenyl sulfone (from a Grignard reagent) in ethereal solution in the presence of cupric chloride in 5% yield has been reported47. Despite the reported48 poor stability of the a-sulfonyl C-centered radicals, Julia and coworkers49 provoked the dimerization (in 13 to 56% yields) of the lithiated carbanion of alkyl phenyl sulfones using cupric salts as oxidants. The best results are obtained with cupric triflates in THF-isobutyronitrile medium (56% yield for R = H). For allyl phenyl sulfones the coupling in the 3-3 mode is predominant. 

Reaction of halides with oxide ion 0-68 Cleavage of oxonium salts 0-79 Reduction of acetals or ketals 0-92 Reaction between Grignard reagents and acetals or ketals dimerization of acetals... 

Scheme 7 displays a possibility of the synthesis of chiral 2-arylpropionic acids via the oxidative tranformation of (7 )-3-aryl-l-butenes. The requisite chiral olefins may be obtained by transition metal-catalyzed asymmetric coupling between a benzylic Grignard reagent and vinyl bromide (93 % optical yield) [28] or, more attractively, asymmetric hydrovinylation of an aromatic olefin with ethylene. The asymmetric combination of styrene and ethylene, giving the adduct 25 in 95 % ee, has been performed on a 10-kg scale with a dinuclear Ni catalyst formed from ( -allyl)NiCl2 and a unique chiral dimeric aminophosphine obtainable from (/ )-myrtenal and (5)-l-phenylethylamine [7a],... 

Gerlach has also prepared pyrenophorin (9) and its meso diastereomer, as shown in Scheme 4.3,The activated thioester 13 was condensed with Grignard reagent 14, affording a 65% yield of ketone 15. After protection of the ketone carbonyl, introduction of the double bond via a selenylation-oxidation sequence produced 16 (36%). Seco acid 17 was obtained in 79% yield by desilylation followed by basic hydrolysis of the ester. Cyclization to the dimer, again under Mitsunobu conditions, afforded a 24% yield of a 1 1 mixture of the protected precursor of 9 and the corresponding meso diastereomer, which were then converted to 9 and 18 by hydrolysis. 

Bakuzis has explored the use of an interesting (B-acrylate anion equivalent in his synthesis of 9 (Scheme 4.5) ° The Grignard reagent from 3-bromopropyl phenyl sulfide was condensed with acetaldehyde and the resulting alkoxide was acylated to procure 24 (70%). Oxidation of the sulfide to aldehyde 25 proceeded in 74% yield. Reaction of 25 with ethyl 3-nitropropionate followed by elimination of HNO2 from the intermediate afforded 26. The latter step, equivalent to the addition of the p-carbanion of ethyl acrylate, occurred in 38% yield. Oxidation of alcohol 26, protection of the resulting ketone, and saponification gave 17. This intermediate was then dimerized as previously described to a mixture of 9 and its meso diastereomer. 

The difficulties of direct oxidative insertion with metals other than Mg or Li mean that o-complexes are often made from organo-lithium or Grignard reagents by metal exchange. This reaction amounts to a nucleophilic substitution at the metal without a change of oxidation state so the metal is used in whatever oxidation state is finally needed. Attack of methyl lithium on a Cu(I) halide gives methyl copper 50, a o-complex of Me- and Cu(I). If an excess of MeLi is present an ate complex is formed, lithium dimethylcuprate 51. This is formally a compound of a copper anion 51a, just as BF4 is a borate. The term ate complex refers to such formally anionic complex in which the metal has one extra anionic ligand. Its true structure is dimeric 51b and it exists as an equilibrium with 52 in solution.20... 

Perhaps the most useful of the r 3 allyl complexes (cf. 24) are the Jt-allyls of nickel.15 The simplest type 61 are rather unstable and form the bromide-bridged complex 62 on treatment with HBr. These are stable compounds officially complexes of Ni(I) but better regarded for our purpose as dimers of r 3 complexes of allyl anions and Ni(II), much as allyl Grignard reagents 2 can be regarded as o-complexes of allyl anions and Mg(II). Direct exchange of Mg(II) for Ni(II) gives the unstable complexes 61, but the stable dimer 62 can be made by oxidative insertion of Ni(0), as its cyclo-octa-1,5-diene (COD) complex, into allyl bromide 1. 

With two equivalents of an organomagnesium halide, a Grignard reagent is formed, capable of use in further syntheses (35,36). Cuprous salts catalyze oxidative dimerization of propargyl alcohol to 2,4-hexadiyne-l,6-diol [3031-68-3] (37). 

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