Diarylmethanols

The reduction is general for a variety of substituted benzophenones Such substituents as CH3 OH, OCH3, F, Br. N(CH3)2, NO2. COOH, COOCH3, NHCOC Hreaction conditions and do not alter the course of the reduction Diarylmethanols are reduced to diarylmethanes under the same conditions and probably are the intermediates in the reduction of ketones [26] Triethylsilane also can be used as a reducing agent in trifluoroacetic acid medium [27J This reagent is used for the reduction of benzoic acid and some other carboxylic acids under mild condiUons (equation 14) Some acids (phthalic, sue cinic, and 4-nitrobenzoic) are not reduced under these conditions [27]... 

Use of ferrocene 9 in combination with the mixed zinc reagent (ZnPh2/ZnEt2 = 1 2) allowed a wide range of diarylmethanols 27 to be prepared in a highly enantioselective manner [38]. A selection of products is shown in Scheme 2.I.2.8. 

The success of the asymmetric aryl transfer from boronic acids also relied on another important phenomenon. The presence of catalytic amounts (10 mol%) of DiMPEG (MW = 2000) increased the enantioselectivity of the process significantly [49]. For example, without DiMPEG the reaction between benzaldehyde 37b and 1-naphthylboronic acid 40c gave the corresponding diarylmethanol 27g with 31% ee in 56% yield, whereas in the presence of the polyether, 27g was obtained in 85% ee and 91% yield (Scheme 2.1.2.12) [49]. 

Obviously, this rhodium-catalyzed diarylmethanol formation with boronic acids still requires significant optimization in order to be competitive with the forementioned existing methodology using phenylzinc reagents, but these early results appear particularly promising. 

The Wittig rearrangement is the base-catalyzed 1.2-shift of an alkyl, allyl. benzyl, or phenyl group of an ether from oxygen to carbon. A patent claim describes the conversion of aryl arylmethyl ethers such as 21 into diarylmethanols such as 22.14... 

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. 

Gribble GW, Leese RM, Evans BE (1977) Reactions of Sodium Borohydride in Acidic Media IV. Reduction of Diarylmethanols and Triarylmethanols in Trifluoroacetic Acid. Synthesis 172... 

It is evident that the incorporation of the diarylmethanol unit induces an —12 nm bathochromic shift in >,max of these compounds with 245 adsorbing at ca. 486 nm and 244 at 474 nm. 

Asymmetric synthesis of diarylmethanols can be achieved via rhodium-catalysed addition of arylboronic acids to benzaldehydes, using chiral mono- or bi-dentate phos- ... 

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. 

T. Yokozawa, and R. Noyori, Selective hydrogenation of benzophenones to benzhydrols. Asymmetric synthesis of unsymmetrical diarylmethanols, Org. Lett. 2000a, 2, 659-662. 

Chiral diarylmethanols have been prepared enantioselectively by phenyl transfer to benzaldehydes, using PhB(OH)2-ZnEt2 and a new tertiary aminonaphthol auxiliary.246... 

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... 

Bohn and coworkers introduced an additional central chiral wingtip group (CHPhMe) onto the other side of the imidazole ring [11] in an attempt to increase the chiral resolution in the product of asymmetric catalysis. For this effect, they reacted phenyl boronic acid with 4-chlorobenzaldehyde to give the corresponding chiral diarylmethanol. Chiral resolution was modest at best with no clear trend as to the additive or competitive nature of the two chiral elements present in the ligand. 

Reduction of diaryl ketones. Diaryl ketones or diarylmethanols are reduced to diarylmethanes by NaBH4 in trifluoroacetic acid (equation I.)" ... 

Underivatized chiral aromatic alcohols, including ArCH(OH)R. ArCHiCHiOHIR. simple tertiary arylalkylcarbinols and nr/Hv-I-arylcyclohexanols. asymmetrically substituted diarylmethanols and 1,1-diarylethanols... 

Diarylmethanols. Diaryliodonium salts can be used to react with aldehydes. Accordingly, reactivity umpolung is manifested. 

The transition metal catalyzed asymmetric addition of aryl organometallic reagents to aldehydes, ketones, and imines has provided efficient access to chiral aryl alcohols or aryl amines [89]. Arylboronic acids are less toxic, stable toward air and moisture, and tolerant towards a variety of functional groups, and are ideal reagents for the addition to aldehydes. However, when Sakai et al. [90] attempted the enantioselective Rh-catalyzed addition of phenylboronic acid to naphthaldehyde, only 41% ee was obtained. Chiral spiro phosphite complex (S)-18c was found to be an efficient catalyst for asymmetric addition reactions of arylboronic acids to aldehydes, providing diarylmethanols in excellent yields (88-98%) with up to 87% ee (Scheme 30) [20c]. 

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. 

The Gribble reduction of diaryl ketones refers to the sodium borohydride-trifluoroacetic acid (NaBHVTFA) reduction of diaryl ketones (1) to diarylmethanes (2).1 The reaction is very general and is applicable to the reduction of diarylmethanols (3) and triarylmethanols (4) to the respective diarylmethanes (2) and triarylmethanes (5).2... 

Following the discovery of the ability of NaBHVRCC H to effect the reduction and N-alkylation of indoles,12 Gribble and co-workers found that diaryl ketones are smoothly reduced to diarylmethanes using NaBFL/TFA.1 A year earlier it was found that diarylmethanols and triarylmethanols are similarly reduced to the respective hydrocarbons.2... 

Consistent with this mechanism is the observed facile reduction of diarylmethanols and triarylmethanols with NaBUt/TFA.2 Other examples of products from the corresponding alcohols are 10-15. The corresponding cations leading to 10—15 are spectacularly colored in TFA (e.g., scarlet-red, red-orange, purple, dark blue, and blue-green). 

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