Diphenylprolinols

An alternative method for generating enriched 1,2-diols from meso-epoxides consists of asymmetric copolymerization with carbon dioxide. Nozaki demonstrated that a zinc complex formed in situ from diethylzinc and diphenylprolinol catalyzed the copolymerization with cyclohexene oxide in high yield. Alkaline hydrolysis of the isotactic polymer then liberated the trans diol in 94% yield and 70% ee (Scheme 7.20) [40]. Coates later found that other zinc complexes such as 12 are also effective in forming isotactic polymers [41-42]. 

Fig. 5.7. Crystal structure of borane complex of a,a-diphenylprolinol oxazaborolidine catalysts. Reproduced from...

The catalyst was prepared by reaction of (iS)-diphenylprolinol with dimethylphosphinite and triethylamine in the presence of carbon tetrachloride. The N-(0,0-dimethylphosphoryl) derivative obtained was treated with an excess of p-anisylmagnesium bromide to give the oxazaphosphinamide catalyst[13]. 

Et2Zn/(i )- diphenylprolinol Copolymerization mejo-epoxide/C02 Strong (-f)-NLE 46... 

For a recovery of (S)-a,a-diphenylprolinol, which is the hydrolysis product of the CBS-catalyst (S)-5 (and likewise its synthetic precursor ), the aqueous phase is carefully adjusted to pH 10 with concentrated ammonia and extracted with diethyl ether (3 x 50 ml). The combined organic layers are washed with brine (50 mL) and dried over MgS04. Removal of the solvent by rotary evaporation yields 1.68 g (79%) of crude (S)-a,a-diphenylprolinol. This material is dissolved in dichloromethane / methanol 9 1 (3 ml) and filtered over Alox B (act. Ill, 80 g) with dichloromethane / methanol 9 1 as the eluent, to yield 1.64 g (77%) of (S)-a,a-diphenylprolinol as a white solid. 

Asymmetric hydrogenation of alkenes is efficiently catalysed by rhodium complexes with chiral diphosphite and diphosphoramidite ligands derived from BINOL or diphenylprolinol. Choice of a proper achiral backbone is crucial.341 Highly enantioselective hydrogenation of A-protected indoles was successfully achieved by use of the rhodium catalyst generated in situ from [Rh(nbd)2]SbF6 (nbd = norborna-2,5-diene)... 

Diphenylprolinol methyl ether catalyses the enantioselective Michael addition of simple aldehydes to simple enones.219... 

A diphenylprolinol derivative, having hydrophobic perfluoroalkyl phase tags, has been synthesized and used as a pre-catalyst to generate in situ a fluorous oxaz-aborolidine catalyst for the reduction of prochiral ketones with borohydride. The system afforded high enantioselectivities and the pre-catalyst is easily separated and recycled.272 Reduction of enantiopure A-p-toluenesulfinyl ketimines derived from 2-pyridyl ketones with sodium borohydride affords A-p-toluenesulfinylamines with good yields and diastereoselectivities.273... 

Diphenylprolinol silyl ethers (17) have been found to be efficient organocatalysts for the asymmetric Michael reaction of aldehydes and nitroalkenes. 

Diphenylprolinol methyl ether (145) catalyses intermolecular Michael addition of simple aldehydes to enones in the absence of solvents with high enantioselectivities (95-99% ee) and significantly lower catalyst loadings (5 mol%) than have been typical in this arena.175... 

In the case of acetophenone reduction, it appears that amino alcohols that are sterically hindered at the carbon adjacent to the alcohol lead to much better results. A dramatic effect has been found in the case of prolinol and diphenylprolinol the enantiomeric excess increases from 50% to 97%. Cyclic amino alcohols where the nitrogen is in a 4- or 5-membered ring have exceptional catalytic properties and lead to very good enantiomeric excesses (Tables 16.1 and 16.2). Diphenylprolinol (4) is a very good choice because of its availability and performance. 

Two different approaches can be followed to prepare and use the catalyst. The first is to prepare it in situ by mixing (R)- or (S)-diphenylprolinol (DPP) (4) and a borane complex (Scheme 16.2). This route is advantageous because there is no need to use boronic acids (or boroxines) and to remove water to form the catalyst. Another possible way is to use preformed catalysts, some of which are commercially available from suppliers such as Callery. 

Diphenylprolinol (4) itself is now commercially available at scale, or it can be prepared several ways (Scheme 16.2) Direct addition of an aryl Grignard reagent to a proline ester leads to the diarylprolinol with a low yield in the range of 20-25%.33 A more efficient route is based on an... 

The oxazaborolidine is finally made by heating diphenylprolinol (4) under reflux with a suitable alkyl(aryl)boronic acid or, better, with the corresponding boroxine in toluene in the presence of molecular sieves—the water can also be removed by azeotropic distillation. According to the literature, methyl-oxazaborolidine (Me-CBS) can be either distilled or recrystallized. The key point is that the catalyst must be free from any trace of water or alkyl(aryl)boronic acid because those impurities decrease enantioselection. 

In the case of H-CBS, this catalyst could be prepared by mixing diphenylprolinol with borane-THF (tetrahydrofuran) or borane dimethylsulfide. Despite numerous efforts in many groups to isolate or even characterize H-CBS by nuclear magnetic resonance spectroscopy, all attempts have been unsuccessful. H-CBS is used in situ, and good results can be obtained in many cases. 

The diphenylprolinol silyl ether 45a catalyst was developed by the Hayashfs group for the addition of a-unbranched aldehydes to aryl and alkyl substituted nitroolefins [35]. This catalyst, as well as the perfluoroalkyl derivative 45b [36],... 

Numerous theoretical treatments have been carried out to understand the mode of asymmetric induction of the Corey-Bakshi-Shibata (CBS) reduction, more thoroughly.12 Liotta et al. carried out computational studies to identify the transition states for CBS reductions of various ketones13 (Scheme 4.3k).In the asymmetric reduction of acetophenone with the catalyst (R)-28a, four transition states were found. Of the lowest energy is chairlike transition state A, which would lead to formation of the major enantiomer. In transition state A, the phenyl group of acetophenone occupies an equatorial position that is free from any steric interaction, as it is 5.5 A away from one of the two phenyl groups of the diphenylprolinol ring. On the other hand, transition state B, leading to the... 

Chi Y, Gellman SH (2005) Diphenylprolinol methyl ether a highly enantioselective catalyst for Michael addition of aldehydes to simple enones. Qrg Lett 7 4253 1256... 

This catalytic cascade was first realized using propanal, nitrostyrene and cinnamaldehyde in the presence of catalytic amounts of (9TMS-protected diphenylprolinol ((.S )-71,20 mol%), which is capable of catalyzing each step of this triple cascade. In the first step, the catalyst (S)-71 activates component A by enamine formation, which then selectively adds to the nitroalkene B in a Michael-type reaction (Hayashi et al. 2005). The following hydrolysis liberates the catalyst, which is now able to form the iminium ion of the a, 3-unsaturated aldehyde C to accomplish in the second step the conjugate addition of the nitroalkane (Prieto et al. 2005). In the subsequent third step, a further enamine reactivity of the proposed intermediate leads to an intramolecular aldol condensation. Hydrolysis returns the catalyst for further cycles and releases the desired tetrasubstituted cyclohexene carbaldehyde 72 (Fig. 8) (Enders and Hiittl 2006). 

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