Enantioselective organocatalytic

Major advances in the application of NHCs in organocatalysis have been achieved, and this arena has become a focus of considerable research. The use of chiral NHCs has allowed access to highly enantioselective organocatalytic transformations and the breadth and depth of reactivity that can be accessed is ever expanding. 

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-... 

An enantioselective organocatalytic 1,3-DC reaction, based on the activation of a,fi-unsaturated aldehydes through the reversible formation of iminium ions with chiral imidazolidinones 100, was described. Good levels of asymmetric induction and diastereocontrol were achieved (up to 94% ee and 94 6 dr) <00JA9874>. 

Enantioselective organocatalytic conjugate additions such as Michael and aldol reactions have been intensely studied under new catalysts. However, only a few organocatalyzed Michael reactions have been developed. The reaction involves construction of a new C-N bond that is very attractive for syntheses of molecules with biological properties. 

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). 

Takemoto and co-workers reported the use of a similarly structured bifunctional catalyst for the first enantioselective organocatalytic Michael addition of malonitrile to... 

The first report of an enantioselective organocatalytic [3+2] cycloaddition between nitrones and a,P-nnsaturated aldehydes was reported by MacMillan and co-workers who showed that iminium ion activation was effective in this reaction (Scheme 8) [64], After a survey of seven catalysts the imidazolidinonium salt 12 HC10 emerged as the most efficient system. The reactions were conducted in a mixture of nitromethane and water at -20 °C in the presence of 20 mol% catalyst... 

Evans CG, Gestwicki JE (2009) Enantioselective organocatalytic Hantzsch synthesis of polyhydroquinolines. Org Lett 11 2957-2959... 

An enantioselective organocatalytic reductive amination has been achieved using Hantzsch ester for hydrogen transfer and compound (21) as catalyst. This mild and operationally simple fragment coupling has been accomplished with a wide range of ketones in combination with aryl and heterocyclic amines.359... 

The use of benzophenone imines of glycine derivatives [19] as substrates in enantioselective organocatalytic alkylation has been developed toward an excellent method for preparation of a wide range of optically active a-amino acids with high enantioselectivity [1, 20],... 

Enantioselective organocatalytic cyclopropanations have been performed using directed electrostatic activation conditions.164 Using a new class of iminium catalysts, cyclopropanation has been conducted with enals but not electron deficient alkenes, such as unsaturated nitrile, nitro, or alkylidene malonate systems. 

A novel method for enantioselective organocatalytic cyclopropanation has been developed, using a new class of iminium intermediates and based on the concept of directed electrostatic activation (DEA). This novel organocatalytic mechanism exploits dual activation of ylide (153) and enal (152) substrates through the formation of the iminium intermediate (155) and electrostatic activation (156). The resulting (g) trisubstituted cyclopropanes (157) were obtained with high levels of enantio- and diastereo-control.180... 

A key step in the total synthesis of the marine metabolite (—)-solanopyrone D (161) is the enantioselective organocatalytic intramolecular Diels-Alder reaction of the trienal (158) to the decalin aldehyde (160) in the presence of the imidazolidinone catalyst (159) (Scheme 45).187 Protonated 1,2-diamino-1,2-diphenylethane has been... 

The direct enantioselective organocatalytic a-fluorination can also be performed with cinchona alkaloid derivatives as catalyst under phase-transfer reaction conditions [25]. The fluorination reaction by NFSI of / -ketoesters 21, readily enolizable substrates, generated a stereogenic quaternary C-F bond in high yields and with enantioselectivities up to 69% ee for the optically active products 26 (Eq. 6). 

The nucleophilic activation of hydrosilanes as HSi(OR)3 offers an opportunity to transfer one hydride on the carbon of ketones or imines [22]. The enantioselective organocatalytic hydrosilylation of ketones was first reported in 1999 by Matsu-mura et al. [23], the catalyst employed being a proline derivative 19 (Scheme 11.7). Amide 20 was also able to catalyze the hydrosilylation of ketimines, as indicated in Scheme 11.7 [24]. Improved results were recently reported by Kocovsky and Maikov [25], who prepared from valine some acyclic analogues of prolina-... 

Enantioselective organocatalytic (with tetrahydro-4//-imidazol-4-one-based catalysts of type 102nHX) 2-alkylation of pyrroles by, -unsaturated aldehydes generates 3-(pyrrol-2-yl) aldehydes 103 (Scheme 46) <2001JA4370, 2002JA1172, 200SJA1S0S1 and references therein>. 

Ahrendt KA, Borths CJ, MacMillan DWC (2000) New strategies for organic catalysis The first highly enantioselective organocatalytic Diels-Alder reaction. J Am Chem Soc 122 4243-4244 Akiyama T (2004) Preparation of chiral Bronsted catalysts in asym. synthesis and asym. Mannich, aza-Diels-Alder reaction, hydrophosphorylation therewith. PCT Int Appl WO 200409675, 2004-11-11... 

Beeson TD, MacMillan DWC (2005) Enantioselective organocatalytic alpha-fluorination of aldehydes. J Am Chem Soc 127 8826-8828 Berkessel A, Groger H (2005) Asymmetric organocatalysis. Wiley-VCH, Weinheim... 

Brochu MP, Brown SP, MacMillan DWC (2004) Direct and enantioselective organocatalytic alpha-chlorination of aldehydes. J Am Chem Soc 126 4108-4109... 

Brown SP, Goodwin NC, MacMillan DWC (2003b) The first enantioselective organocatalytic Mukaiyama-Michael reaction a direct method for the synthesis of enantioenriched gamma-butenolide architecture. J Am Chem Soc 125 1192-1194... 

Itoh T, Nagata K, Miyazaki M, Ishikawa H, Kurihara A, Ohsawa A (2004) A selective reductive amination of aldehydes by the use of Hantzsch dihydropy-ridines as reductant. Tetrahedron 60 6649-6655 Jen WS, Wiener JJM, MacMillan DWC (2000) New strategies for organic catalysis The first enantioselective organocatalytic 1,3-dipolar cycloaddition. J Am Chem Soc 122 9874-9875... 

Kunz RK, MacMillan DWC (2005) Enantioselective organocatalytic cyclopro-panations. The identification of a new class of iminium catalyst based upon directed electrostatic activation. J Am Chem Soc 127 3240-3241 Lacour J, Hebbe-Viton V (2003) Recent developments in chiral anion mediated asymmetric chemistry. Chem Soc Rev 32 373-382 Li X, List B (2007) Catalytic asymmetric hydrogenation of aldehydes. Chem Commun 17 1739-1741... 

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... 

Development of the First Highly Enantioselective Organocatalytic Reduction of Ketimines... 

Chen XH, Xu XY, Liu H, Cun LF, Gong LZ (2006) Highly enantioselective organocatalytic Biginelli reaction. J Am Chem Soc 128 14802-14803 Cordova A (2004) The direct catalytic asymmetric mannich reaction. Acc Chem Res 37 102-112... 

MacMillan DWC, Ahrendt KA, Borths CJ (2000) New strategies for organic catalysis the first highly enantioselective organocatalytic diels-Alder reaction. J Am Chem Soc 122 4243-4244... 

Partially or fully saturated thiophene derivatives have also attracted some interest, and several new routes to such systems have been developed during the passed year. An enantioselective organocatalytic approach to substituted tetrahydrothiophenes has been... 

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>. 

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