Enantioselectivity C-H coupling

In 2012, Itami and Yamaguchi discovered the bisoxazoHne-Pd catalysts such as 173 and 174 that enable the synthesis of hindered heterobiaryls by direct C-H coupling. Moreover, they demonstrated the first enantioselective C-H biaryl cross-coupling (Scheme 17.49) [227]. For example, when an n-PrOH solution of thiophene 175 and arylboronic acid 176 was treated with a Pd(OAc)2/biox 174 catalyst and TEMPO at 70 °C under air, (S)-177 was obtained in 41% ee (63% yield). When a more hindered arylboronic add 178 was used, the enantiometric excess of product (S)-179 was increased to 72% at the expense of lower yield. 

Based on extensive studies of C-H transformation with Pd(ii), Yu et al. recently achieved asymmetric desymmetrization in a CDC reaction (Scheme 7.26). ° Boc-L-Isoleucine (Boc-Ile-OH) was an effective chiral ligand for the Pd(ii)-catalyzed enantioselective C-H activation of a,a-diphenylacetic acid Na salt. The resultant Pd-aryl intermediate is considered to undergo insertion into styrenes or acrylates, followed by p-hydrogen elimination to afford the coupling product with a chiral quaternary carbon center in good... 

The berberine bridge enzyme (BBE) was employed for the first preparative oxidative biocatalytic C-C coupling (Scheme 8.71). Racemic N-methyl THIQs (rac-146) was enantioselectively converted by BBE in toluene/buffer co-solvent under aerobic conditions. The sp -sp C-H coupling products (S)-147, berbine derivatives, and unreacted (R)-146 were obtained with high ee, accomplishing highly efficient kinetic resolution. 

Enantioselective C—H activation/C C cross-couplings using chiral palladium catalysts, and boronic acids was recently reported. In a remarkable study, Yu and coworkers demonstrated the desymmetrization of prochiral C—H bonds on geminal aryl or methyl groups with monop-rotected amino acids as a source of chirality and pyridine as the directing group.Benzoquinone promoted both the... 

SCHEME 13.21. Enantioselective C-H activation/C-C cross-couplings using chiral palladium catalysts and boronic acids. 

The enantioselective oxidative coupling of 2-naphthol itself was achieved by the aerobic oxidative reaction catalyzed by the photoactivated chiral ruthenium(II)-salen complex 73. 2 it reported that the (/ ,/ )-chloronitrosyl(salen)ruthenium complex [(/ ,/ )-(NO)Ru(II)salen complex] effectively catalyzed the aerobic oxidation of racemic secondary alcohols in a kinetic resolution manner under visible-light irradiation. The reaction mechanism is not fully understood although the electron transfer process should be involved. The solution of 2-naphthol was stirred in air under irradiation by a halogen lamp at 25°C for 24 h to afford BINOL 66 as the sole product. The screening of various chiral diamines and binaphthyl chirality revealed that the binaphthyl unit influences the enantioselection in this coupling reaction. The combination of (/f,f )-cyclohexanediamine and the (R)-binaphthyl unit was found to construct the most matched hgand to obtain the optically active BINOL 66 in 65% ee. 

Examples of oxidative coupling to vinyl derivatives remain limited in number, however, because the reaction takes a different course whenever allylic hydrogen atoms are present in a substrate (Scheme3, f andg). Under these conditions allylic sp3 C-H bonds are activated and such reactions are therefore allylic oxidations (SectionIV.1.2.4). In recent years, however, several examples of reactions of type g (Scheme 3) have been performed enantioselectively and called asymmetric... 

There are a couple of examples of cascade processes starting by a Michael-type addition of a carbon nucleophile proceeding under phase-transfer eatalysis conditions which deserve to be mentioned at this point. The first one eonsists of an enantioselective cyclopropanation of 2-bromocyclopentenone by a cascade Michael/intramolecular nucleophilic displacement in which a variety of C-H acidic carbon pro-nucleophiles such as nitromethane, cyanomethylsulfone and benzyl cyanoacetate reacted with this Michael acceptor in the presence of a quinidinium salt of type 67 (Scheme 7.79). In addition, the conditions needed to be optimized for each Michael donor employed, requiring a different catalyst and inorganic base for each case. Under the best conditions, the final cyclopropanes were obtained in moderate yields and enantioselectivities, albeit as single diastereoisomers. 

In 2010, Gong and co-workers reported a Lewis acid-catalyzed enantioselective oxidative cross-coupling reaction of 3-indolylmethyl C—H bonds... 

In 1999, Mikami and co-workers reported the first example of asymmetric Fujiwara-Moritani reaction catalyzed by Pd" and sulfonylamino-oxazoline ligand (Scheme 5.12a). A 1 1 complex between the chiral ligand and Pd(OAc)2 could be the active catalyst in this asymmetric Fujiwara-Moritani reaction. This method provides a convenient process to synthesize aromatic C—H bond activation/olefin coupling products but with moderate enantioselectivity. 

The pioneer work of enantioselective C(sp )—H bond functionalization featuring a Pd /Pd catalytic cycle was first reported by Baudoin, Clot, and cowvorkers. The electronwvithdrawing group in the ortho position of substrate 83 was crucial to obtaining the p-arylation product (Scheme 5.31). Furthermore, aryl chlorides are also able to be the coupling partners although the reactions have to be performed at an elevated temperature. The intermolecular arylation products were synthesized in moderate yields and ee. However, it provides a blueprint for developing more efficient catalytic systems. 

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