Biaryl, axially chiral

The hydrogenation of allylic alcohols and a,/>-unsaluraled acids leads to products with a very high synthetic potential, and both transformations were used quite early for industrial applications. In both cases Ru complexes with axially chiral biaryl ligands (binap analogues) are the catalysts of choice. Here, we will dis-... 

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). ... 

The axially chiral biaryl 4-DMAP 32 developed by Spivey [117-127] is relatively readily prepared but only provides modest levels of selectivity for the KR of aryl alkyl ec-alcohols < 30 at -78 °C over 8-12 h or < 15 at room temperature in 20 min (Table 4) [119],... 

Maruoka has found that simple alcohols can also be used in the oxy-Michael reaction [107], Using the axially chiral biaryl catalyst 67 (1 mol%) the conjugate addition of methanol, ethanol and aUyl alcohol to a, 3-unsaturated aldehydes was examined (Scheme 29). Despite moderate yields (55-83%) and enantioselectivities (16-53% ee), the high activity of this catalyst suggests that further optimisation... 

However, a more exciting application of this reaction is the oxazoline-directed synthesis of axially chiral biaryls. The oxazoline system not only activates the ortho-methoxy group for nucleophilic displacement but also determines the stereochemical outcome of the reaction. This provides a convenient method for the introduction of axial-chirality. Meyers group continues their earlier lead on this subject with reports of the stereoselective synthesis of tetrasubstituted biphenyls 391,392 examples are shown in Table 8.29 (Scheme 8.154). The best... 

Substituted dibenzothiophenes 156 react with Grignard reagents to give products of the thiophene ring cleavage. With a chiral Ni catalyst, axially chiral biaryl compounds 157 can be obtained in high enantioselectivities (equation 93) . ... 

F.2.2. Asymmetric Cross-Coupling of Aryl Grignard Reagents Forming Axially Chiral Biaryls... 

Despite growing importance of axially chiral biaryls as chiral auxiliaries in asymmetric synthesis, direct synthetic methods accessing to the enantiomerically enriched biaryls from achiral precursors are still very rare, Application of asymmetric cross-coupling to construction of the chiral biaryls is one of the most exciting strategies to this goal. The reported application... 

Three types of reaction systems have been designed and applied for the enantioposition-selective asymmetric cross-coupling reactions so far. First example is asymmetric induction of planar chirality on chromium-arene complexes [7,8]. T vo chloro-suhstituents in a tricarhonyl("n6-o-dichlorobenzene)chromium are prochiral with respect to the planar chirality of the 7t-arene-metal moiety, thus an enantioposition-selective substitution at one of the two chloro substituents takes place to give a planar chiral monosubstitution product with a minor amount of the disubstitution product. A similar methodology of monosuhstitution can be applicable to the synthesis of axially chiral biaryl molecules from an achiral ditriflate in which the two tri-fluoromethanesulfonyloxy groups are enantiotopic [9-11]. The last example is intramolecular alkylation of alkenyl triflate with one of the enantiotopic alkylboranes, which leads to a chiral cyclic system [12], The structures of the three representative substrates are illustrated in Figure 8F.1. 

The ferrocenylphosphine-nickel catalysts are also applied to asymmetric synthesis of axially chiral biaryl compounds through the cross-coupling reaction. Although initial attempts to this... 

Uemura and Kamikawa have presented a review on the stereoselective synthesis of axially chiral biaryls utilizing planar chiral (arene)chromium complexes [44]. 

In the asymmetric synthesis of axially chiral biaryls, the formation of two C-O bonds is the key step in the etherification of 2,2, 6,6 -tetrahydroxybiphenyl 187 (Scheme 21). Sequential etherification of the biaryl 187 with 1,4-di-O-benzyl-L-threitol 188 under the Mitsunobu conditions afforded the monoether 189. After deprotection of the /-butyldimethylsilyl (TBDMS) group with Bu4NF, the intermediate alcohol was again subjected to the Mitsunobu reaction in situ. The intramolecular cyclization proceeded smoothly to give 190 in high yield (for R= Bn, m.p. 138-139°C) <2000JOC1335>. 

Approaches to the 1,4-dioxocines have been greatly improved during the last decade. Intermolecular condensation with the formation of two C-O bonds is an efficient route to 1,4-dioxocine ring system, particularly in the synthesis of numerous axially chiral biaryls. Intramolecular cyclization with the formation of a C-C bond, particularly by means of the RCM strategy, opened a new avenue in the synthesis of eight-membered 1,4-diheterocines with demonstrated success in the approaches to 1,4-dioxocines with a variable substitution pattern. 

Schrock reported catalysts related to (97c) with a variety of substituents at the 3,3 position of the octahydrobinaphtholate ligand including benzhydryl, (97f), and mesityl, (97g) (Scheme 15). This ligand type is easier to access than either biphenol or binaphthol derived species, since the axially chiral biaryl construct is already in place and substitutions are nearly... 

Other Compounds. In theory, any chiral compound with a reactive functional group can be derivatized with (5)- or (R)-MTPA in order to assess its enantiomeric purity. An example is the derivatization of cyclic carbamates, followed by H NMR analysis (eq 1). Similarly, axially chiral biaryls bearing amine or alcohol substituents, e.g. (16) and (17), have been analyzed via the corresponding MPTA derivatives. ... 

Bringman et al. have investigated biaryl lactones and biaryl thionolactones as precursors to enantiomerically enriched axially chiral biaryls. Both, the lactones and the thionolactones are configurationally labile. In this method, biaryl products are obtained by coordination of a Lewis acid followed by reductive lactone ring cleavage. Asymmetric induction requires either the Lewis acid or the reducing agent to be chiral. Both approaches have been realized for biaryl thionolactones with mild Ru Lewis acids (Scheme 10.18) [29]. 

Investigation of an enantioselective version of this using brucine instead of DABCO showed that the coupling of j9-naphthylamines with naphthyUead triacetate derivatives proceeded at even lower temperatures (-78 to -4() fi) to give the axially chiral biaryls with moderate enantioselectivity (Scheme 13.24) [25 b]. 

New work on the asymmetric hetero DA reaction as a route to 2,3-dihydropyran-4-ones includes the use of axially chiral biaryl-based diols <05JA1336> and chiral Bronsted acids <05TL6355> which work through hydrogen bonding. Polymer-bound Danishefsky s diene derived from acetoacetate has been used in the hetero DA reaction with aldehydes. With a chiral BINOL-Ti(IV) complex, good yields of 2-aryl-5-methoxycarbonyl-5,6-dihydropyran-... 

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