Diaryl prolinol

This asymmetric version of Levy s disconnection exploits diaryl prolinol 141 as a catalyst to induce the enantioselective formation of tetra-hydro(iminoethano)carbazole 142 from vinylindole 139 and trans-formyla-crylate 140. The sequence proceeds via a similar mechanism as that seen in Scheme 9. 

Scheme 7.1 Asymmetric epoxidation of tra/rs-enals and frans-chalcone by OTMS diaryl prolinol/H202 and r-diphenyl prolinol/TBHP s tems, respectively.

Scheme 7.4 Supported and recyclable diaryl prolinol/TBHP systems for the asymmetric epoxidation of trtzzzs-enones.

The diaryl prolinol/TBHP system has been found to be suitable for the asymmetric epoxidation of a variety of poorly investigated trans-disubstituted or trisubstituted electron-poor alkenes (Scheme 7.5). ... 

Scheme 7.5 Substrate scope of the diaryl prolinol/TBHP-catalysed asymmetric epoxidation.

Bromomalonate, selected as the pronucleophile, is proposed to undergo deprotonation by the diaryl prolinol catalysts lej to give the corresponding reactive enolate involved in the conjugate addition with different electron-poor alkenes (Scheme 7.9). The intramolecular alleviation proceeds with more nucleophilic indandione-derived enolate, under one-pot conditions, in... 

Scheme 7.9 Asymmetric Michael initiated ring closure reactions of a-bromo mal-onates and electron-poor alkenes to functionalised cyclopropanes catalysed by diaryl prolinols.

Figure 8.1 The most common diaryl prolinol silyl ether organocatalysts Cla and C2a.

Asymmetric organocatalysis mediated by a,a-l-diaryl prolinols (2009— 2012) 13CC3821. 

SCHEME 11.3. Silyl-protected diaryl prolinol (7)-catalyzed a-amination of a-unbranched aldehydes with azodicarboxylate esters via enamine catalysis. 

Chiral tetrahydrothiophenes are compounds displaying important biological activities. They were obtained also through an enantioselective domino sulfa-Michael-Michael process of a,(3-unsaturated aldehydes with ethyl 4-mercapto-2-butenoate [47]. While catalyst 17a turned out to be ineffective, the diarylprolinol silyl ether 17b afforded cyclic products with high to excellent enantio- and diastereoselectivity (Scheme 14.16a). A closely related sulfa-Michael aldol process was developed by using 3-mercapto a-carbonyl esters as reaction partners. The best stereoselectivity and yield were obtained with diaryl prolinol 17c in the presence of small amounts of H2O (Scheme 14.16b) [48]. 

Zhu and co-workers [76] reported readily available secondary amines, such as a,a-L-diaryl prolinols, catalyzed a-sulfenylation of cyclic (3-ketoesters with commercially available Af-(phenylthio) phthalimide, and other 7V-aryl phthalimides. Products were formed after short reaction times in good to high yield and enantio-selectivity (Scheme 14.27). 

The same group expanded the scope of the reaction treating cyclic p-keto phos-phonates and catalyst 17c with different A-(arylthio) phthalimides (Scheme 14.27) [77]. Fairly good results in terms of yield and enantiocontrol were achieved for the first preparation of the thiophosphonates in enantiomerically enriched form. It is interesting to note that noncovalent activation provided by diaryl prolinols expands the potential of secondary amines in promoting asymmetric reactions of carbonyl compounds other than simple aldehydes and ketones. A major limitation of all... 

The same enamine activation strategy was later applied to develop the first successful catalytic asymmetric a-selenylation of aldehydes by Melchiorre, Marini, and co-workers [79]. Aldehydes were reacted with A-(phenylseleno)phthalimide in the presence of 5 mol% loading of O-TMS diaryl prolinol 17a and / -N02C6H5C02H as co-catalyst. Selenyl alcohols were selectively recovered, after in situ reduction, in high yield and excellent enantioselectivity (Scheme 14.28). 

In 2008, the groups headed by Jprgensen and Rueping contemporaneously reported the use of 1,3-diketones reacting as bis-nucleophiles with a,p-unsaturated aldehydes under iminium catalysis with a diaryl prolinol sdyl ether catalyst (Scheme 16.13) [27, 28]. This domino reaction allowed the formation of 3,4-dihydropyrans with good yields and enantioselectivities but variable diastereoselectivities in favor of the 1,3-trans derivatives, precursors of indoloquinoUzidines [29]. 

A wide-ranging enantio- and diastereo-selective reaction of imines and aldehydes gives anP-Mannich product. For example, PhCH2CH2CH=NTs reacts in brine with both aliphatic and aromatic aldehydes. A simple diaryl prolinol TMS ether serves as chiral catalyst A-nosyl imines can also be employed. ... 

Branched enals have been aziridinated enantioselectively using a diaryl prolinol TMS ether as catalyst, giving IV-tosyl aziridines with a quaternary centre." ... 

On the other hand, diaryl prolinol silyl ethers have been applied as orga-nocatalysts for the asymmetric Mannich reaction of acetaldehyde with N-benzoyl-, iV-Boc- and iV-Ts-imines in the presence of para-aiirobtnzoic acid in THF. The generated (3-amino aldehyde products were isolated in good to high yields and excellent enantioselectivities (95-98% ee) after conversion into the corresponding alcohols by reduction with L1A1H4 (Scheme 3.10). 

Scheme 3.10 Mannich reactions of acetaldehyde catalysed by diaryl prolinol sUyl ether.

Chloro-l,2-diones (110) undergo a domino Michael/aldol with enals (111) to give highly functionalized cyclopentanones (112), using diaryl prolinol TMS ethers as organocatalysts. The best de/ee/yidd results were 90/94/97%. A fluoro-substrate gives a cyclopentenone product, that is, the dehydration equivalent of (112). 

Finally, a remarkable four-component tandem Michael-aza-Henry-hemi-aminalisation-dehydration tandem reaction was recently developed by Lin and co-workers on the basis of a dual organocatalysis involving a chiral diaryl prolinol trimethylsilyl ether and a chiral cinchona alkaloid." As shown in Scheme 2.37, the reaction began with the Michael addition of an aldehyde to a nitroalkene catalysed by the L-proline-derived catalyst, giving the corresponding intermediate aldehyde. The latter intermediate... 

Diamination was first reported in 2007 by Jprgensen and coworkers with a combination of enamine and iminium-ion activation modes catalyzed by the diaryl prolinol silyl ether 3 (10 mol%) [18]. The sequential addition of succinimide as the nucleophile and diethyl azodicarboxylate as the electrophile afforded the syn-diaminated products 32 and 33 in promising overall yield (40%) with high levels of stereoselectivities (dr up to 8/2, ee 99%) (Scheme 12.14). 

Other proline-derived catalysts promoting the selective formation of the fl/iti-diastereomer have been developed, for example, by the groups of Maruoka (axially chiral amino sulfonamides 98, symmetric chiral pyrrolidine-based amino sulfonamides 99) [66, 67] and Cdrdova (diaryl-prolinols 100) [68], among others, involving Coulombic or steric interactions (or both) as well to lock the transition state in the conformation required for stereoselective catalysis (Figure 11.3). 

Acetaldehyde 34, which is the simplest of all enolizable carbonyl compounds but highly reactive as an electrophile, is an inexpensive and versatile two-carbon nucleophile in enamine-based Mannich reactions. Mannich reactions of acetaldehyde as a donor with aryl or alkyl substituted N-Boc-imines 90 are effectively catalyzed by (S) -proline (13) in moderate yield but excellent enantioselectivity (Table 28.6, entries 1 and 2) [47]. Chemical yields are improved up to 87% when N-benzoyl (Bz)-imine is employed in the presence of diaryl prolinol silyl ether 85 with p-nitrobenzoic acid (entry 3) [48]. To suppress side reactions, such as self-aldol reactions, the moderate nucleophilicity of the axially chiral amino sulfonamide 23 is particularly useful for this type of Mannich reaction these conditions give the corresponding adducts 91 in good yield and excellent stereoselectivity (entries 4 and 5) [49]. 

Iminium catalysis is one of the most powerful methods for the introduction of a nucleophile in -position of an a,(3-unsaturated carbonyl. Various nucleophiles can be entered such as N, O, C, aryl, and heteroaryl nucleophiles in usually high levels of stereoselectivity. To obtain these high enantioselectivities, two catalysts have seemed to be more general as soon as aldehydes are involved. Diaryl-prolinol silyl ethers and MacMillan imidazolidinones have found applications in numerous processes (Scheme 11.3). These catalysts are... 

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