Diarylmethanol derivatives

One of the governing principles in the TADDOL system is the conformational lock and steric bias provided by the geminal diarylmethyl group. The question arises whether there are other chiral auxiliaries exploiting this gem-iml-diaryl effect. Indeed there are some are shown in Scheme 17. We expect to see more examples for the preparation and use of diarylmethanol derivatives in EPC synthesis and other chirality-creating processes. 

Baoeffl/, [59] andKappeefaZ. [60] independendy reported the synthesis of diarylmethanol derivatives using nickel catalysts, 2ildehydes, and arylboronic acid derivatives. While Bao and coworkers used Ni(C10, )2 OH O along with as base, with a maximum yield of 92%, Kappe and coworkers... 

In 2002, Ha and coworkers [72a] reported the preparation of binaphthyl-based amino alcohols (Figure 7.9, C) and their application in the asymmetric diphenylzinc additions to aldehydes. The corresponding diarylmethanol derivatives were obtained with very high enantioselectivities (92—98% ee) and in excellent yields (95—98%). Curiously, aliphatic aldehydes were tested as well, but poorer enantioselectivities were obtained (66—68% ee). 

Moreover, when the reaction was performed with a multifunctional substrate, such as 4-acetyl-benzophenone (85), the yield in diaryl methanol was 1.3 times higher than that derived from the reduction of the acetyl group. On the other hand, when the non-imprinted polymer was used, the regioselectivity was reversed, with the yield of reduced acetyl being 1.7 times higher than the diarylmethanol. 

The direct addition of in situ-prepared arylzinc to aldehydes with chiral binaphthyl-derived amino alcohols (24) as catalysts has afforded optically active diarylmethanols in high yields and with excellent enantioselectivities (up to 99% ee).106 By using a single catalyst, both enantiomers of many pharmaceutically interesting diarylmethanols can be obtained by the proper combination of various arylzinc reagents with different aldehydes. 

The pXr values of diarylmethyl cations [22C ] were basically those determined according to the same method as for the triarylmethyl cations in aqueous sulphuric acid solutions by Deno and coworkers (Deno et ai, 1955 Deno and Schriesheim, 1955 Deno and Evans, 1957). For reasons of solubility, a wide set of pXr+ values in aqueous acetic acid solutions were determined by Mindl and coworkers (Mindl and Vecera, 1971, 1972 Mindl, 1972). Unfortunately, however, the pXr+ values, determined by means of the protonation-dehydration method for diarylmethanols, could only be obtained for more stable derivatives and not for those less stable than the unsubstituted... 

When the Hammett plot bends the other way, so that the rate of the reaction decreases as it passes the discontinuity, we have a single mechanism with a change in rate-determining step. A reaction goes by the fastest possible mechanism but its rate is limited by the slowest of the steps in that mechanism. An example is the intramolecular Friedel-Crafts alkylation of a diphenyl derivative where the alkylating agent is a diarylmethanol attached to one of the benzene rings in the ortho position. 

Diarylmethanols and triarylmethanols are reduced in high yield to the corresponding methanes by NaBH4 in trifluoroacetic acid. Kabalka and co-workers have now extended the use of catecholborane to effect regiospecific deuterium incorporation via the reduction of tosylhydrazones to the corresponding methylene derivatives. ... 

The synthesis of diarylmethanol-based 1,4-diols and enantiomerically pure 1,1-bi-2-naphthol (BlNOL)-derived diols has been reported via a neighbouring lithium-promoted [1,2]-Wittig rearrangement (Scheme 51). ... 

With the goal of exploring the efficiency of NHC-type ligands in this particular catalytic reaction, Ma and coworkers [12], in 2010, synthesized several planar chiral imidazolium salts derived from [2.2]paracyclophane (Figure 7.3). By using these imidazolium salts as carbene precursors, the rhodium-catalyzed 1,2-addition of arylboronic acids to aldehydes proceeded readily with low catalyst loadings (0.03-0.3 mol%) and afforded a variety of diarylmethanols in excellent yields but in low to moderate enantioselectivities (a maximum of 52% ee was achieved). 

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