Prolinol catalysts

An exploration of structural modifications on the activity of prolinol catalysts has been published <06T12264>. More electron-rich aromatic rings on the prolinol scaffold improve the activity in the epoxidation of a, 3-enones. The reaction of 10 with an enone and f-BuOOH provides the epoxy-ketones with moderate levels of enantioselectivity. 

A recoverable fluorous prolinol catalyst has been developed for enantioselective reduction of ketones. 309 ... 

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... 

Heterofunctionalisation of carbonyl compounds in the a-position has become an important facet of oiganocatalytic enamine-mediated reactions. In 2005, the Jorgensen group described asymmetric a-sulfenylation of aliphatic aldehydes using TMS-protected prolinol catalysts. The best sulfenylating agent was M-benzylsulfanyl-1,2,4-triazole. Other catalysts, such as proline, prolinol, prolinamide or other secondary amide were less effective. The catalyst with bulkier aromatic groups (C2a) afforded the most enantioselective reaction (Scheme 8.39). 

Organocatalysts were also reported in the synthesis of azepines. In this way, a-ketoamides 8 were reacted with a,p unsaturated aldehydes 9 and a prolinol catalyst 11 to form oxobridged azepine derivatives 10 with good stereocontrol. 

In 2009, Nakamura and co-workers [8] developed an organocatalytic aldol reaction between acetaldehyde 4 and dibromoisatin 1 catalyzed by iV-heteroaryl-sulfonylprolinamide 5, to achieve (/ )-convolutamydine E (6) in high enantioselectivity, which was easily converted to (/ )-convolutamydine B (7) (Scheme 17.2). In the same year, the Hayashi group used the prolinol catalyst 10 for the synthesis of enantiomer of natural convolutamydine E ent-6) (Scheme 17.3) [9], and intermediate 12 could be easily transformed into CPC-1 (13), a new pyrrolidinoindoline alkaloid isolated by Takayama and co-workers [10]. In addition, 12 was easily converted to indoline fragment 14, a key intermediate for the syntheses of madindo-line A (15) and B (16), which are selective inhibitors of interleukin-6, isolated from the fermentation broth of Streptomyces nitrosporeus K93-0711 by Omura and coworkers [11]. 

As depicted in Scheme 7, the synthesis of the mosquito oviposition pheromone (-)-6-acetoxy-5-hexadecanolide (28) via an intermolecular aldol reaction represents a powerful demonstration of the high potential of asymmetric enamine catalysis (45, 46). It is noteworthy that a methodologically different successful organocatalytic approach towards 28, based on an asymmetric a-oxygenation, was reported recently (727). Reaction of aldehyde 136 with dibenzoyl peroxide (BzOOBz) and hydroqui-none (HQ) (722) in the presence of the TMS-protected prolinol catalyst (S)-138 followed by a direct allyation gave the benzoyl-protected 139 in moderate yield and good selectivity. Intermediate 139 could then be further transformed to give (—)-(57 ,65)-6-acetoxy-5-hexadecanolide (28) (Scheme 33). 

Allylic alcohols RCH=CHCH20H can get engaged in a triple-domino process, commencing with oxidation to RCH=CHCH=0, catalysed by the Fe complex (255), followed by iminium formation with the prolinol catalyst (256a), addition of a cyclic... 

A shift from 1,4- to 1,6-addition of azlactones and butyrolactones to 2,4-dienals has been achieved with prolinol catalysts (256), which can exercise full control of the newly generated stereocentre six bonds away from the stereocentre. With BocNHOTs, this concept has been applied to remote aziridination of dienals (275) ... 

Woggon et al. synthesized a-tocopherol in an enantioselective manner, demonstrating the synthetic utility of decarbonylation (Scheme 8.15) [64]. o-Hydroxybenzaldehyde 76 was reacted with a,P-unsaturated aldehyde 77 in the presence of a prolinol catalyst to afford the hemiacetal 78. Oxidation followed by hydrogenolysis gave the carboxylic acid 80, which was reduced to the aldehyde 81. Treatment with a catalytic amount of Rh(dppp)2Cl under a N2 stream... 

Hyunsoo Han of the University of Texas, San Antonio has described Tetrahedron Lett. 2007, 48,7094) an improved protocol for the enantioselective conversion of primary aUy-Uc carbonates 16 to secondary amines 17. Rene Peters of ETH Zurich has used (Angew. Chem. Int. Ed. 2007,46,7704) a related procedure for the construction of aminated cpiater-nary centers. Mukund P. Sibi of North Dakota State University has devised J. Am. Chem. Soc. 2007,129, 8064) a catalyst for the conjugate addition of the benzyloxyamine 20 to acyl pyrazoles, and Claudio Palomo of the Universidad de Pais Vasco has found (Angew. Chem. Int. Ed. 2007, 46, 8054) that a simple diphenyl prolinol catalyst will effect enantioselective a-amination of aldehydes. 

I 2 TMS-Prolinol Catalyst in Organocatalysis Formal cycloaddition reactions (as "diene") ... 

In addition to pyrrolidine-based structure, prolme-based catalysts were also investigated. Two examples of supported prolinamide-based catalysts for the Michael reaction are 86 and 87 (Figure 24.29). Prolinamide-bridged silsesquioxane 86 was prepared from a bis-sUylated prolinamide by sol-gel methodology and used in water. This catalytic material was also used in aldol reactions [108]. The prolyl-prolinol catalyst 87 was anchored to a polystyrene backbone and used in a dichloromethane/water mixture [22a]. 

Alternatively, a,a-diaryl prolinol catalysts 22 (5 mol%) in combination with /1-nitrobenzoic acid or catalyst 15a (20 mol%) could be used to promote the a-selenenylation of aldehydes using A-(phenylseleno)phtalimides as electrophile [113]. For this reaction, toluene was the solvent of choice and the in situ reduction of the obtained product to the corresponding alcohol was needed in order to preserve the achieved levels of enantioselectivities (Scheme 4.15). A wide range of aldehydes, including alkyl, alkenyl and heterosubstituted aldehydes were suitable substrates, affording the expected products 79 with excellent enantioselectivities. 

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