Biaryl-substituted alcohol

Scheme 19.24 One-pot synthesis of a biaryl-substituted alcohol based on combination of Suzuki cross-coupling reaction and alcohol dehydrogenase-atalyzed reduction.

A simple, commercially available chiral alcohol, a,a,a a -tetraaryl-l,3-dioxo-lane-4,5-dimethanol (TADDOL, 7a), catalyzes the hetero- and carbo-Diels-Alder reactions of aminosiloxydienes with aldehydes and a-substituted acroleins to afford the dihydropyrones and cyclohexenones, respectively, in good yields and high enan-tioselectivities. More recently, it was reported that axially chiral biaryl diols 7b and 7c were more highly effective catalysts for enantioselective hetero-Diels-Alder reactions (Scheme 12.5). ... 

Somewhat between diastereoselective and enantioselective approaches is the Cram s synthesis involving the oxazolines with chiral alkoxide leaving groups [26]. In this manner, bromine in oxazoline 596 was substituted with sodium alkoxides, derived from readily available natural alcohols such as menthol (597), fenchyl alcohol (598), bomeol (599), quinine (600), and quinidine (601) to give the respective chiral oxazolines 602-606, Scheme 10. The Meyers reaction of oxazolines 602-606 and 1-naphthylmagnesium bromide (608) was effected at low temperatures (-42 °C) affording the expected biaryl 609 with respective chiral induction. 

Many electrochemical approaches to biaryls, e.g., electroreductive dimerization of aryl halides [12, 13] and electrooxidative dimerization of arylboronic acids [14], have been investigated. Substituted or non-substituted benzoic acids are electrochemically reduced to the corresponding alcohols or aldehydes. For instance, electroreduction of /M-phenoxybenzoic add proceeds smoothly to afford m-phenoxybenzaldehyde, an intermediate for insecticide [2,15]. 

Regioselectivity can usually be reliably obtained when two of the alkyne partners are tethered. A Cp RuCl(cod)-catalyzed intermolecular cyclotrimerization of three different monoalkynes could be performed by an in situ-tethering approach with the formation of a temporal C-B-O linkage from alkynylboronates and propargyl alcohols [13-15] [Eq. (9)]. The resultant arylboronates could not be isolated and were further converted to substituted biaryls via the Suzuki-Miyaura coupling or into a sequential one-pot process [14], or to phtalides via a palladium-catalyzed carbonylation [15]. 

Nishii et al. reported metal-mediated benzannulation reaction of diaryl(gm-dichlorocyclopropyl)methanols to synthesize unsymmetrically substituted a-arylnaphthalenes [61]. In particular. The reaction of optically active alcohol 145 in the presence of 1 equiv of HCU at —78 °C afforded chiral biaryl 146 with an excellent level of stereo induction (Scheme 27.48) [62]. It should be noted that chi-raUty exchange from sp central chiraUty to axial chirality takes place in this process. This methodology has been employed successfully for total synthesis of natural lignin lactones, justicidin B, and dehydrodesoxypodophyllotoxin (Scheme 27.49) [63]. 

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