Benzylic coupling

Somewhat mysteriously, the Pd-catalyzed alkynyl-allyl and alkynyl-benzyl coupling reactions had until recently been elusive. This limitation has been overcome142,143 over the last several years, as discussed in Section III.C.l.c. 

SCHEME 63. Synthesis of coenzyme Q (n lO) and menaquinone-3 via Pd- or Ni-catalyzed alkenyl-benzyl coupling with alkenylalanes... 

There are very few reports on the aryl-allyl or aryl-benzyl coupling reaction, but these combinations are very popular in other organometalHcs (Scheme 38). Arylation of allyl acetates or carbonates was catalyzed by NiCl2(PPh3)2 or NiCl2(dppf) with net inversion of the stereochemistry of the C-0 bond for... 

Scheme 38. Aryl-allyl and aryl-benzyl coupling...

VIII. Anomalous Couplings Electrophilic Radicals, Benzylic Couplings. 143... 

VIII. ANOMALOUS COUPLINGS ELECTROPHILIC RADICALS, BENZYLIC COUPLINGS... 

Benzylic coupling in substituted methylpyrazines (687) and the influence of side chain alkyl substitution on benzylic coupling constants (1500) have been examined. On the basis of the methyl replacement technique, within its inherent limitations, the para-benzylic coupling appeared to be rr-electron transmitted. 

Morphine and related alkaloids are specific to the genus Papaver (Berberidaceae), although the antipodal series of alkaloids is distributed in the Menisperma-ceae. Early in the biosynthesis of morphine, an inversion at C-1 of (5)-reticuline occurs, followed by ortho-para benzylic coupling to afford salutaridine. Stereospecific reduction and cyclization-elimination affords the 4,5-Ether bridge and thebaine. The dominant pathway from this point involves neopinone, codeinone, codeine, and morphine. Again, most of the enzymes in this sequence were isolated and characterized by Zenk s group (Fig. 30). 

Application of the Pd-catalyzed alkenyl-allyl coupling to totally regio- and stereo-controlled synthesis of a-farnesene [92] and a recent synthesis of coenzymes Q3 and Q5 via Ni-catalyzed alkenyl-benzyl coupling [103] demonstrate the synthetic utility of this novel allylation and benzylation methodology (Schemes 1-29 and 1-30). 

The fate of the alkyl radicals produced under these conditions is a function of the nature of R. If R is an aralkyl, such as benzyl, coupling occurs to give mostly dimers in fact, preparative coupling of aralkyl halides by >j -Cp2V has been demonstrated . It appears that alkanes, alkenes, and H2 form if R is aliphatic and j -hydrogen atoms are available - . 

Compound (28) presents an unusual long range V( H— H) coupling constant between pyrazole H3 and =CH protons <87AP(320)115>. A systematic study of ortAo-benzylic coupling constants 7Me-c=c-H has been published <92JHC935> 1,3-dimethylpyrazole (—0.55 Hz), 1,4-dimethylpyrazole... 

Oxidative phenol-benzyl coupling. The key step in a new total synthesis of ( )-picropodophyllone (3) involves oxidation of the phenol 1 with thallium(III) trifluoroacetate in the presence of BF3 etherate in CH2CI2 at 20°. After work-up, which included bisulfite reduction and methylation, the diester (2) was obtained in 55% yield. Some evidence suggests that the cyclization proceeds through a p-quinone methide (a). 

OXIDATIVE PHENOL-BENZYL COUPLING Thallium(III) trifluoroacetate. 

C.ii.b. Aryl-Benzyl Coupling. In contrast with the corresponding Pd- or Ni-catalyzed benzyl-aryl coupling, the range of satisfactory metals in the arylmetals is broader, and Zn, Sn, and B have been successfully used. The absence of comparative data does not permit their objective comparisons. 

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