Enones enantioselective organocatalytic

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... 

Chiral N heterocyclic carbenes (NHCs), as Lewis basic organocatalysts, have been synthesized and applied to enantioselective organocatalytic reactions in recent years. Encouraged by Sheehan and Hunneman s first report of chiral thiazolium salts as NHC precursors for organocatalytic reactions [37], Leeper, Enders, Rovis, Glorius, Herrmann, and others have synthesized series of novel chiral NHCs with mono cyclic, bicyclic, or tricyclic backbones [38]. Recently, a series of bifunctional NHCs were synthesized and applied to aza BMH reaction of cyclopent 2 enone with... 

A highly enantioselective organocatalytic Michael addition of 4-hydroxycouma-rines and related compounds to a,p-unsaturated ketones has been also achieved using imidazolidine catalyst 137 [213]. The reaction, which gives high yields and enantioselectivities for a wide range of cyclic 1,3-dicarbonyl compounds and enones, has been successfully employed for the asymmetric synthesis of the anticoagulant warfarin (Scheme 2.78) and derivatives [213], With respect to the reaction mechanism, very recent studies have demonstrated that the truly active catalyst in the process was the chiral diamine 138, which is formed in catalytic amounts under the reaction conditions by reaction with the hydroxycoumarine (Schane 2.79)... 

Scheme 2.77 Enantioselective organocatalytic conjugate addition of malonates to acyclic a,p-unsaturated enones catalyzed by 106...

A bifunctional iminiumyhydrogen-bonding catalysis has been very recently employed for the first enantioselective organocatalytic conjugate addition of a phosphorous nucleophile (diarylphosphane oxides) to a,ji-unsaturated ketones [370]. The process, which allows efficient additions to cyclic and linear enones as well as the generation of quaternary stereocenters, is catalyzed by quinine-derived thiourea... 

Falck and co-workers [87] developed an enantioselective organocatalytic oxa-Michael addition of phenylboronic acid to )//S-hydroxy-a,)6-enones, catalyzed by a... 

Li DR, Murugan A, Falck JR (2008) Enantioselective, Organocatalytic 0 y-Michael Addition to y/8-hydroxy-a,P-Enones Boronate-Amine Complexes as Chiral Hydroxide Synthmis. J Am Chem Soc 130 46... 

Peelen TJ, Chi YG, Gelhnan SH (2005) Enantioselective Organocatalytic Micltae/ Additions of Aldehydes to Enones with Imidazolidinones Cocatalyst Effects and Evidence for an Enamine Intermediate. J Am Chem Soc 127 11598... 

Indole-fused pyran-4-ones are prepared in one-pot two-step synthesis. In the first there is the acylation of 1-substituted 3-acetyl-lH-indol-2-ols with acid chlorides using triethylamine as base, in dichloromethane at room temperature. The second consists in the 4ff-pyran-4-one ring formation firom the in situ-obtained 3-acetyl-2-acyloxy-lF/-indole derivatives (13S1235).A highly diastereo- and enantioselective organocatalytic formal hDA reaction of enones with isatins occurs in the presence of amine 34, acid 35, and thiourea 36 to produce spirooxindole tetrahydro-4ff-pyran-4-ones (Scheme 59) (13CEJ6213). 

Later, the first enantioselective organocatalytic transfer hydrogenation involving cyclic enones was reported by MacMillan and co-workers following an operationally simple and rapid protocol that allowed access to chiral / -substituted... 

Another important reaction by which to form C-C bonds is the nitroalkane Michael addition. The first attempt to obtain a nitroalkane enantioselective addition to enones was reported by Yamaguchi in 1994, using as a catalyst rubinate salts of proline. The first truly enantioselective organocatalytic addition of nitroalkanes to enones was developed by Hanessian using proline as catalyst in the presence of an amine additive. The reaction affords good yields and enantioselectivities when cyclic enones were used (up to 93% ee) however, the addition to chalcones renders the products in lower enantioselectivities (up to 68% ee) [90]. 

The first enantioselective organocatalytic oxo-Michael reaction to enones was reported by Falck [109]. Falck developed the intramolecular addition of boronic acids hemiesters to enones catalyzed by thiourea catalysts. Alkyl, aryl, and heteroaryl y-hydroxy enones react with phenylboronic acid to furnish the corresponding boronic hemiesters 118, which after oxidative cleavage of the resulting dioxaboro-lane renders the chiral 1,2 diols 119 in excellent yields and enantioselectivities (Scheme 33.34). 

BOTH (Enantioselective Organocatalytic Transfer Hydrogenation) The group led by MacMillan showed that the combination of an imidazolidine catalyst 3 and a Hantzsch ester 4a is a powerful and versatile reducing agent (Scheme 32.2). They were able to selectively reduce 1,4-unsaturated enals and enones with yields up to 95% and ees up to 97%. 

An efficient and highly enantioselective, organocatalytic aza-Michael addition of JV-substituted diethyl thionophosphoramidates (84) to enones... 

The organocatalytic transfer hydrogenation of cyclic enones has been also successfully achieved employing the imidazolidinone 12 [24], catalyst that also promotes enantioselective Diels-Alder reactions with cyclic enones [25]. The structure of the dihydropyridine reagent seems to have an important effect on the selectivity of the process since better enantioselectivities are observed when increasing the steric hindrance of the ester moiety 13 (Scheme 2.6). The reduction, which is performed with substoichiometric amounts of imidazolidinone 12 in ether at 0°C,... 

Scheme 2.81 Organocatalytic enantioselective conjugate additions to enones catalyzed by bifhnc-tional thiourea 109...

Few examples have been reported for the organocatalytic asymmetric conjugate addition of sulfur nucleophiles other than thiols. The reaction of thiocarboxylic acids to cyclohex-2-enones [390] and a,p-nnsatnrated esters [391] was initially studied by Wynberg et al. employing Cinchona alkaloid catalysts with limited success in terms of selectivity (up to 54% ee). Slightly better enantioselectivities have been recently obtained by Wang et al. in the 1,4-addition of thioacetic acid to P-nitrostyrenes (up to 78% ee) [392] and trani-chalcones (up to 65% ee) [393], using Takemoto s thiourea 142 as catalyst (2-10 mol%). 

J0rgensen and Juhl reported the first organocatalytic enantioselective inverse-electron-demand hetero-Diels-Alder reaction of aldehydes (e.g., 71) and enones (e.g., 72) with excellent diastereo- and enantioselectivity. Scheme 3.26 [41], The reaction utilizes a chiral enamine intermediate as an alkene in catalytic asymmetric cycloaddition reactions. 

Scheme 3.71 Organocatalytic and enantioselective 1,3-dipolar cycloaddition of cyclic enones and...

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