Enantioselective organocatalysts

Enantioselective organocatalysts were the first to be used as nonenzymatic catalysts in the early twentieth century. The literature on organocatalysts was reviewed in 2001. ... 

Protected sulfenylation reagents (Lg-S-Pg) a-sulfenylate aldehydes, using steri- cally encumbered chiral pyrrolidines as enantioselective organocatalysts.298... 

The tert-butyldiphenylsilylojqr L-serine (OTBDPS-L-Ser) was a highly efficient enantioselective organocatalyst when used at a loading of 10 mol% in... 

C. Menozzi and PI. Dalco, Chapter 5 in Enantioselective Organocatalysts, Wiley-VCH, Weinheim, 2007. 

A hypervalent silicon complex, generated from silicon tetrachloride and a chiral phosphine oxide, acts as an enantioselective organocatalyst of the MBH reaction, by asym- q. metric delivery of a chloride anion as a nucleophile. ... 

Figure 31.4 Highly enantioselective organocatalysts for the aza-MBH reaction of a,[ unsaturated aldehydes.

Pei D, Zhang Y, Wei S, Wang M, Sun J. Rationally-designed S-chiral bissulfinamides as highly enantioselective organocatalysts for reduction of ketimines. Adv. Synth. Catal. 2008 350 619-623. 

Enantioselective alcoholysis of racemic, prochiral, or meso cyclic anhydrides can be catalyzed by hydrolases, yielding the corresponding monoesters (Eigure 6.25). In most cases, the enantioselectivity was moderate ]75-77]. Organometallic catalysts or organocatalysts such as cinchona alkaloids are often more efficient than enzymes for the stereoselective ring opening of cyclic anhydrides. 

New organocatalysts prepared by the Jacobsen group showed that alkylation of the final amide bond increased the enantioselection (Scheme 38, compare R2 = Me, 98% ee to R2 = H, 91% ee). Thus, the reaction performed with N-allyl benzaldimine and with the dimethylamide-ending thiourea (Scheme 38 with Ri = R2 = Me) gave up to 99% ee. This compound is a structural analogue of the urea depicted in Scheme 36 [148,152,154]. 

Both the ureas and thioureas are highly suitable organocatalysts for the asymmetric Strecker synthesis. For example, the thiourea function was replaced by an urea function (note the opposite configurations). The organocatalysts thus obtained showed similar activity and slightly higher enantioselec-tivities with N-allyl benzaldimine (Scheme 39,74% yield with 95% ee for Ri = Bn and R2 = H). Once again, better enantioselectivity (up to 99% ee) was at-... 

An enantioselective aza-Henry reaction catalysed by the same bifimctional organocatalyst was recently reported by the same group (Scheme 47) [163]. 

In a recently published report by MacMillan s group [121] on the enantioselective synthesis of pyrroloindoline and furanoindoline natural products such as (-)-flustramine B 2-219 [122], enantiopure amines 2-215 were used as organocatalysts to promote a domino Michael addition/cyclization sequence (Scheme 2.51). As substrates, the substituted tryptamine 2-214 and a, 3-unsaturated aldehydes were used. Reaction of 2-214 and acrolein in the presence of 2-215 probably leads to the intermediate 2-216, which cyclizes to give the pyrroloindole moiety 2-217 with subsequent hydrolysis of the enamine moiety and reconstitution of the imidazolid-inone catalyst. After reduction of the aldehyde functionality in 2-217 with NaBH4 the flustramine precursor 2-218 was isolated in very good 90 % ee and 78 % yield. 

In the 1990s, short peptides,and other nucleophiles °° ° were used as organocatalysts for a number of enantioselective acyl transfer processes transformations that set the stage for the more recent research in the area of nucleophilic catalysis.One of the most appealing approaches to enantioselective acyl transfer was outlined by Fu using an azaferrocene catalyst (6) [Eq. (11.6)]. While these pyridyl systems are not organic catalysts in the strictest sense, these azaferrocene compounds function as chiral dimethylaminopyridine equivalents for a broad range of acyl transfer processes ... 

Groger has also reported a preliminary study on enantioselective acetyl migration in the Steglich rearrangement using one of Fu s commercially available catalysts and Birman s tetramisole-based organocatalyst [108]. 

This review will concentrate on metal-free Lewis acids, which incorporate a Lewis acidic cation or a hypervalent center. Lewis acids are considered to be species with a vacant orbital [6,7]. Nevertheless, there are two successful classes of organocatalysts, which may be referred to as Lewis acids and are presented in other chapter. The first type is the proton of a Brpnsted acid catalyst, which is the simplest Lewis acid. The enantioselectivities obtained are due to the formation of a chiral ion pair. The other type are hydrogen bond activating organocatalysts, which can be considered to be Lewis acids or pseudo-Lewis acids. 

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