Enantioselective arylation

Enantioselective arylation of ketones can be realized either with the standard BINAP ligand, which requires harsh conditions and a high loading of catalyst to produce high yields (53),202 or with newer, MOP-type ligands (L4) (Section 9.6.3.4.2) under mild conditions and only one-tenth as much catalyst., 204... 

Two strategies for the synthesis of enantiomerically enriched diaryl methanols 27 are apparent first, asymmetric reductions of the corresponding diaryl ketones 36 [33], and, second, enantioselective aryl transfer reactions to the respective benzaldehyde derivatives 37 (Scheme 2.1.2.5) [34, 35]. 

The transmetallation from (PhBO)3 to diethylzine has been shown to occur in a two-step process (Scheme 9.16). This catalytic system is highly effective for the enantioselective arylation of aldehydes to give diaryl carbinols. ... 

A catalytic enantioselective arylation of arylaldehydes employs a chiral /3-amino alcohol and a boronic acid-diethylzinc exchange reaction to generate the reactive arylzinc species.247... 

Asymmetric Heck-type ary lotion.1 A catalyst prepared in situ from Pd(OAc)2 and (R)-BINAP effects a highly enantioselective arylation of 2,3-dihydrofuran with aryl triflates with diisopropylethylamine as base and benzene as solvent. Two products (2 and 3) are formed with opposite configurations. The highly enantioselective formation of the major product (2) is ascribed to a kinetic resolution step which converts the enantiomer of 2 into 3. 

More recently, Liao et al. showed a comparison between Pd-complexes of different biaryl-linked bisphosphines possessing varied dihedral angles. Scheme 15, in an enantioselective arylation of methylindanone (82). The result not only demonstrates the effect of the dihedral angle on enantioselectivities but also illustrates the influence of the electronic properties on the achieved enantioselectivity. The DIFLUORPHOS ligand (81) having a narrower dihedral angle and poor... 

Another noteworthy development is an asymmetric synthesis of chiral biaryls by a Pd-catalyzed enantioselective aryl-aryl coupling reaction of prochiral 2,6-bis(triflyloxy)biaryls [62], Using Cl2Pd[(53-Phephosl as a chiral catalyst, the first phenylation of l-[2,6-bis(triflyloxy)phenylJnaphthalene with PhMgBr proceeds in 85% ee. As might be expected, the minor enantiomer is the more reactive of the two in the second phenylation. This leads to a kinetic resolution, and the desired monophenylated enantiomer can be obtained in 93% ee. Similarly favorable enantioselective alkynylation results have also been reported [180]. 

BORONIC ACIDS AS ARYL SOURCE FOR THE CATALYSED ENANTIOSELECTIVE ARYL TRANSFER TO ALDEHYDES... 

The chiral phosphoric acid (127) has been found an effective organocatalyst for the direct enantioselective arylation of ethyl triffuoroacetate and ethyl 4 4 4-triffuoroacetoacetate with indoles (133) in which a series of chiral triffuoromethyl-substituted tertiary alcohols (134) were obtained in moderate to high yields with good enantioselectivities (55-78% ee) (Scheme 33). ... 

Chan VS, Bergman RG, Toste FD (2007) Pd-catalyzed dynamic kinetic enantioselective arylation of silylphosphines. J Am Chem Soc 129 15122-15123... 

There are two major realizations of the polar pathway in intermolecular Mizoroki-Heck reactions (1) enantioselective arylation of cyclic alkenes (Chapter 11) and (2) regioselective internal arylation of terminal alkenes (Chapter 3). 

Modern aspects of electrophilic aromatic substitution chemistry address the development of enantioselective variants of these direct (hetero)arene functionalization reactions. For example, enantiomerically enriched metal catalysts, as well as organocatalysts, allowed for the asymmetric addition reactions of (hetero)arenes onto (a,P-unsaturated) carbonyl compounds. Additionally, highly enantioselective arylations of carbonyl compounds were accomplished with organometallic reagents... 

Fu reported the first enantioselective arylation protocol of aldehydes 1 involving diphenylzinc as aryl source and chiral azaferrocene-based ligand 3 (Scheme 8.1 ... 

The first rhodium-catalyzed enantioselective arylation was described by Miyaura in 1998 (Scheme 8.5) [13]. The reaction between 1-naphthaldehyde (13) and phenylboronic acid (14) was catalyzed by a rhodium complex of the monodentate phosphine fSj-MeO-MOP (15), and resulted in the formation of diarylmethanol... 

Figure 8.3 Examined ligands for the rhodium-catalyzed enantioselective arylation of aldehydes.

Enantioselective Arylation of Aryl-Alkyl-Substituted Ketones... 

Intramolecular enantioselective arylation reactions of ketones 29 were described by Lu (Scheme 8.10) [27]. The cationic (BINAP)-palladiumhydroxo complex 30 works in combination with a basic anion-exchange resin as an additive to afford optically active cycloalkanols 31 in high yields and enantioselectivities. 

Pioneering studies of the catalytic, enantioselective arylation of imines date back to 2000, when Hayashi disclosed a rhodium/phosphine-catalyzed addition of arylstannanes to N-tosylarylimines (31). Whereas, the method gave rise to highly enantioenriched diarylmethylamines, five equivalents of the stannane were required to obtain high yields. 

Scheme 8.14 Rhodium-catalyzed enantioselective arylation of imines 42.

Scheme 8.23 Rhodium/diene-catalyzed enantioselective arylation of maleimide 96.

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