Suzuki reaction enantioselective reactions

Shibasaki and coworkers [87] described the first enantioselective combination of this type in their synthesis of halenaquinone (6/1-162) (Scheme 6/1.43). The key step is an intermolecular Suzuki reaction of 6/1-159 and 6/1-160, followed by an enantioselective Heck reaction in the presence of (S)-BINAP to give 6/1-161. The ee-value was good, but the yield was low. 

Ferrocenyl-based ligands comprise a versatile class of auxiliaries because they can be easily modified at the benzylic position with retention of configuration and can incorporate both central and planar chiralities. The appropriate balance of steric and electronic factors has provided ferrocenyl derivatives featuring chelating P,N properties that proved beneficial in numerous enantioselective transformations [50]. Among more recent applications, they could be utilized very efficiently in Pd-catalyzed hydrosilylation (14 >99% ee) [51] and hydroboration (>94% ee) [52] of olefins, allylic amination (99 % ee) [53], Suzuki cross coupling reactions (Section 2.11) [54], and enamide hydrogenation (>99% ee) [55]. 

Enantioselective synthesis of axially chiral biaryls include all approaches where the starting material is achiral and the chirality is induced by an influence of chiral catalyst or reagent. Among enantioselective reactions that have been successfully used in the synthesis of axially chiral biaryls are the Kharasch reaction [34-36], Suzuki-Miyaura reaction [37,38], oxidative phenolic coupling mediated by copper complexes... 

Fortunately, by fine tuning of the reactivity of the different functionalities, not only the combination of a Mizoroki-Heck with a Suzuki reaction but also a Suzuki with a Mizoroki-Heck reaction is possible, even in an enantioselective manner. 

Boron derivatives of heteroarenes are also viable partners. A Suzuki reaction of a vinyl triflate 2.282, prepared by enantioselective enolate formation, with a benzothiophenyl boronic acid 2.283 was used to prepare 12.75 kg of a tropane derivative 2.284 (as its tartrate salt) as a drug candidate (Scheme 2.90). ... 

In biatyl synthesis, although transition metal catalyzed aryl-aryl crosscoupling reactions have been widely exemplified using Suzuki-type reactions, CDC reactions between sp C-H bonds leading to sp C-C bonds are scarce. In 2010, Katsuki reported an enantioselective CDC reaction between two naphthol moieties catalyzed by a chiral iron(salan) complex under aerobic oxidative conditions (Scheme 4.23). Using 4 mol% of the iron(salan) complex 23-A as the catalyst in toluene at 60 °C for 48 h, two different 2-naphthols were coupled and the cross-coupled derivatives were isolated with moderate yields (44-70%) and good ee (87-95%). It must be pointed out that the homocoupling derivatives are also obtained in low yields. 

An enantioselective total synthesis of (+)-phomactin A (181) has been recently reported by Halcomb using intramolecular Suzuki coupling of a B-alkyl-9-BBN derivative to prepare the macrocycle in the final step [162,163], Thus, a regioselective hydroboration of the terminal olefin in the precursor 182 gave an internal alkyl-borane that was cyclized using modification of Johnson s conditions [164], The reaction illustrates the mildness of the Suzuki reaction since the coupling was carried out in the presence of the sensitive dihydrofuran ring (Scheme 3.95). 

Pu and co-workers incorporated atropisomeric binaphthols in polymer matrixes constituted of binaphthyl units, the macromolecular chiral ligands obtained being successfully used in numerous enantioselective metal-catalyzed reactions,97-99 such as asymmetric addition of dialkylzinc reagents to aldehydes.99 Recently, they also synthesized a stereoregular polymeric BINAP ligand by a Suzuki coupling of the (R)-BINAP oxide, followed by a reduction with trichlorosilane (Figure 10).100... 

In concurrent and independent work, Suzuki and Enders found that tethered keto-aldehydes undergo highly enantioselective cross-benzoin reactions using tria-zolium based catalysts [50, 51], The scope includes various aromatic aldehydes with alkyl and aryl ketones (Table 4). Additionally, aliphatic substrate 39a is cyclized in excellent enantioselectivity, albeit in 44% yield. 

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