Enantioselectivity cross-coupling

The use of chiral bidentate phosphines (such as BINAP) in enantioselective cross-coupling reactions has been described, though only modest stereoselectivity has been achieved.431... 

The sequential approach is also common in proposals written by synthetic chemists (a multistep synthesis is inherently step by step). Vyvyan (excerpt 13N), for example, proposes a strategy to synthesize a select group of heliannuols (alleo-pathic natural products isolated from the sunflower) in an optically pure form. One approach that he will explore involves enantioselective cross-coupling reactions between an alkyl zinc reagent and an aryl bromide. He begins with experiments that will utilize recently developed catalysts and produce products with known optical rotation data. Subsequent reactions are described that will lead potentially to the desired stereospecific heliannuols A and D. 

Scheme 52. Enantioselective cross-coupling of naphthols in the presence of the chiral amine sparteine and copper(ll).

Scheme 56. Enantioselective cross-coupling of 2-naphthol catalyzed by copper(ll)/sparteine.

Scheme 14.5 Ni-catalysed enantioselective cross-couplings of benzylic bromides and secondary alkylzinc reagents.

A one-pot oxidative and enantioselective cross-coupling reaction of aldehyde and nitromethane employs diphenylproUnol TMS-silyl ether as organocatalyst the catalyst helps generate both an enamine and an a,j8-unsaturated iminium ion. ... 

Scheme 3-183. Enantioselective cross-coupling of phenylsilanes with or-bromo...

Nickel-catalyzed enantioselective cross-couplings of racemic secondary benzylic halides with organozinc reagents have been further extended to the synthesis of chiral indanes. Indanes are useful building blocks for the synthesis of a variety of bioactive substances. For example, (/ )-3-ethylindanone 129 has been used for the preparation of the nonsteroidal androgen receptor agonist LG 121071. Fu and co-workers have reported on the rapid preparation... 

SCHEME 13.35. Nickel-catalyzed enantioselective cross-coupling in the preparation of the nonsteroidal androgen receptor agonist LG 121071. 

SCHEME 13.36. Enantioselective cross-coupling in the synthesis of dihydrofolate reductase inhibitor 136. 

The chemo- and enantioselective cross-coupling of two different aldehydes via a benzoin reaction remains a significant challenge. Four different benzoin products can be formed (two homo- and two cross-benzoin products), each as two possible enantiomers. The challenge is compounded by the commonly observed reversibility of the reaction. 

Wang and co-workers have developed enantioselective cross-coupling reactions of Waryl tetrahydroisoquinolines (538) with diethyl ethoxy-carbonylmethylphosphonate (539), catalysed by a chiral BOX(541)/Cu" complex, for the synthesis of Cl-modified tetrahydroisoquinolines (540)... 

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