Aldehydes organocatalytic addition

L2909>. An organocatalytic addition of 2-trimethylsilyloxyfuran to aldehydes using 10 mol% of l,3-bis(3-(trifluoromethyl)phenyl)urea provided adducts with modest threo selectivity <06TL8507>. A syn-selective, enantioselective, organocatalytic vinylogous Mukaiyama-Michael addition of 2-trimethylsilyloxyfuran to (E)-3-... 

One of the most interesting developments in recent years is the non-enzy-matic, enantioselective, organocatalytic addition of hydrogen cyanide to aldehydes. This reaction is, for example, very efficiently catalysed by optically pure diketopiperazines, such as cydo-(f )-Phe-(i )-His), which are readily accessible from the corresponding amino acids. [114-116]... 

Garcia-Ruano JL, Marcos V, Aleman J. The organocatalytic addition of bis(arylsulfonyl)methane to a, -unsaturated aldehydes and the synthesis of optically-enriched 3-methyl-alkanols. Chem. Commun. 2009 (29) 4435-4437. 

Highly enantioselective organocatalytic Mannich reactions of aldehydes and ketones have been extensively stndied with chiral secondary amine catalysts. These secondary amines employ chiral prolines, pyrrolidines, and imidazoles to generate a highly active enamine or imininm intermediate species [44], Cinchona alkaloids were previonsly shown to be active catalysts in malonate additions. The conjngate addition of malonates and other 1,3-dicarbonyls to imines, however, is relatively nnexplored. Snbseqnently, Schans et al. [45] employed the nse of Cinchona alkaloids in the conjngate addition of P-ketoesters to iV-acyl aldimines. Highly enantioselective mnltifnnctional secondary amine prodncts were obtained with 10 mol% cinchonine (Scheme 5). 

List gave the first examples of the proline-catalyzed direct asymmetric three-component Mannich reactions of ketones, aldehydes, and amines (Scheme 14) [35], This was the first organocatalytic asymmetric Mannich reaction. These reactions do not require enolate equivalents or preformed imine equivalent. Both a-substituted and a-unsubstituted aldehydes gave the corresponding p-amino ketones 40 in good to excellent yield and with enantiomeric excesses up to 91%. The aldol addition and condensation products were observed as side products in this reaction. The application of their reaction to the highly enantioselective synthesis of 1,2-amino alcohols was also presented [36]. A plausible mechanism of the proline-catalyzed three-component Mannich reaction is shown in Fig. 2. The ketone reacts with proline to give an enamine 41. In a second pre-equilib-... 

The Strecker reaction [1] starting from an aldehyde, ammonia, and a cyanide source is an efficient method for the preparation of a-amino acids. A popular version for asymmetric purposes is based on the use of preformed imines 1 and a subsequent nucleophilic addition of HCN or TMSCN in the presence of a chiral catalyst [2], Besides asymmetric cyanations catalyzed by metal-complexes [3], several methods based on the use of organocatalysts have been developed [4-14]. The general organocatalytic asymmetric hydrocyanation reaction for the synthesis of a-amino nitriles 2 is shown in Scheme 5.1. 

Asymmetric addition of ketenes to aldehydes is a highly attractive synthetic access to yfi-lactones with perfect atom economy [134, 135]. This reaction can be catalyzed efficiently by using chiral amines as organocatalysts. As early as 1967 Borr-mann et al. described an organocatalytic asymmetric ketene addition to aldehydes [136] chiral tertiary amines, in particular (—)-N,N-dimethyl-a-phenylethylamine or (—)-brucine, were used as catalysts [136]. The resulting lactones were obtained with modest enantioselectivity of up to 44% ee. 

Asymmetric sulfur-ylide-type epoxidation is an excellent tool for enantioselective and diastereoselective synthesis of epoxides. By use of Aggarwal-type methodology a broad range of aromatic, enolizable, and base-sensitive aldehydes can be converted into the desired epoxides. In addition to an excellent diastereomeric ratio, the optimized organocatalytic systems of this sulfur-ylide-type epoxidation also... 

Although dimeric Sharpless ligands as catalysts showed impressive results in related organocatalytic transformations, they provided only limited success in asymmetric MBH reactions (Scheme 5.12) [70]. These compounds are bifunctional catalysts in the presence of acid additives one of the two amine function of the dimers forms a salt and serves as an effective Bronsted acid, while another tertiary amine of the catalyst acts as a nucleophile. Whereas salts derived from (DHQD)2PYR, or (DHQD)2PHAL afforded trace amounts of products in the addition of methyl acrylate 8a and electron-deficient aromatic aldehydes such as 27, (DHQD)2AQN, 56, mediated the same transformation in ee up to 77%, albeit in low yield. It should be noted that, without acid, the reaction afforded the opposite enantiomer in a slow conversion. 

Triethoxysilyl acetylene (51) allows a new organocatalytic approach toward the introduction of the alkyne moiety via a nucleophilic addition to aromatic aldehydes, ketones, and aldimines, with EtOK as catalyst (10 mol%). Although a catalytic asymmetric version has not yet been developed, the application of a chiral auxiliary, in the case of imines 53 (Scheme 7.9), led to an impressively high dia-stereoselectivity (20 1) [54], unparalleled by other acetylenic organometallics. 

Paras NA, MacMillan DWC (2002) The enantioselective organocatalytic 1,4-addition of electron-rich benzenes to alpha,beta-unsaturated aldehydes. J Am Chem Soc 124 7894-7895... 

Peelen TJ, Chi Y, Gellman SH (2005) Enantioselective organocatalytic Michael additions of aldehydes to enones with imidazolidinones cocatalyst effects and evidence for an enamine intermediate. J Am Chem Soc 127 11598— 11599... 

Enantioselective organocatalytic conjugate addition of benzo[A] furan-2-boronic acid to ap-unsaturated aldehydes was utilized to synthesize 2-substituted benzo[Z>]furan with a chiral side chain as illustrated below <07JA15438>. Asymmetric syntheses of 2,2-disubstituted dihydrobcnzo b furans were also achieved by a palladium(II)-catalyzed cyclization of 2-allylphenols in the presence of chiral bisoxazolines <07TL4083 07TL4179>. 

A ry -selective, organocatalytic, enantioselective vinylogous Mukaiyama-Michael addition of 2-trimethylsilyloxyfuran to a,/ -unsaturated aldehydes to produce 7-butenolides was achieved by using a chiral amine catalyst... 

Besides the Michael addition of heteroatomic nucleophiles initiating cyclocondensations, acceptor substituted unsaturated systems can also be reacted with carbon nucleophiles stemming from aldehydes in the sense of an umpolung, generally referred to as the Stetter reaction [244-246]. This process is organocatalytic and furnishes in turn 1,4-dicarbonyl compounds, intermediates that are well suited for Paal-Knorr cyclocondensations giving rise to furans or pyrroles. Among numerous heterocycles furans and pyrroles have always been the most prominent ones since they constitute important classes of natural products [247-249], of synthetic... 

Direct organocatalytic asymmetric aldol reaction of a-aminoaldehydes 35 with other substituted aldehydes furnishes S-hydroxy-a-aminoaldehydes with high anti-stereoselectivity. This procedure is of importance for the synthesis of a-aminosugars and derivatives. Additionally, the oxidation of aldehydes gives rise to highly enantiomerically enriched ant/-/3-hydroxy-a-amino acids (O Scheme 28) [156]. 

The less well-studied 3-silyloxyfuran was shown to react with aldehydes in an aldol addition manner under Lewis acidic conditions. High 5yn-diastereoselectivity was obtained with bulky aldehydes <05OL387>. 4-Alkoxy-3-lithio-2-silyloxyfurans reacted with a variety of electrophiles to form 3-substituted tetronates after acidic hydrolysis <05SL2735>. Furans and 2-trimethylsilyloxyfuran are effective nucleophiles in the organocatalytic tandem... 

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