[...]... aminations (List 2002 a; Kumaragurubaran et al 2002 ; Bøgevig et al 2002 b), hydroxylations (Brown et al 2003 a; Zhong 2003 ; Hayashi et al 2003 c, 2004 ; Bøgevig et al 2004 ; Yamamoto and Momiyama 2005 ), alkylations (Vignola and List 2004 ), chlorination (Brochu et al 2004 ; Halland et al 2004 ), fluorination (Enders and Hüttl 2005 ; Marigo et al 2005 c; Steiner et al 2005 ; Beeson and MacMillan 2005 ), bromination... (List 2002 a; Kumaragurubaran et al 2002 ; Bøgevig et al 2002 b), nitrosobenzene (O = N) (Brown et al 2003 a; Zhong 2003 ; Hayashi et al 2003 c; Hayashi et al 2004 ; Bøgevig et al 2004 ; Yamamoto and Momiyama 2005 ), and Michael acceptors (C = C) (Hechavarria Fonseca and List 2004 ; List et al 2001 ; Halland et al 2002 ; Peelen et al 2005 ; Chi and Gellman 2005 ; Betancort and Barbas 2001 ; Alexakis and Andrey 2002 ;... Sekiguchi et al 2003 ; Bøgevig et al 2003 ), Mannich reactions (List 2000 ; List et al 2002 ; Hayashi et al 2003 a; Córdova et al 2002 c; Hayashi et al 2003 b; Córdova 2003 ; Notz et al 2003 ; Enders et al 2005 ; Ibrahem et al 2004 ) and Michael additions (List et al 2001 ; Enders and Seki 2002 ) have been developed (List 2004 ; Allemann et al 2004 ) Scheme 1 Organocatalytic cycles New Concepts for Organocatalysis 5 Scheme... addition reactions with a variety of electrophiles In addition to carbonyl compounds (C = O), these include imines (C = N) in Mannich reactions (List 2000 ; List et al 2002 ; Hayashi et al 2003 a; Córdova et al 2002 c; New Concepts for Organocatalysis 9 Scheme 6 Enamine catalysis of nucleophilic addition reactions Hayashi et al 2003 b; Córdova 2003 ; Notz et al 2003 ; Enders et al 2005 ; Ibrahem et al 2004 ), azodicarboxylates... initiated with the discovery of the prolinecatalyzed direct asymmetric intermolecular aldol reaction about 30 years later (List et al 2000 ; also see Notz and List 2000 ) Since then, prolinecatalyzed enantioselective intermolecular aldol reactions (Northrup and MacMillan 2002 a; Bøgevig et al 2002 a; Chowdari et al 2002 ; Córdova et al 2002 a,b; Sekiguchi et al 2003 ; Bøgevig et al 2003 ), Mannich reactions (List 2000 ;... have been developed subsequently and include enantioselective α-chlorinations (Brochu et al 2004 ; Halland et al 2004 ), α-fluorinations (Enders and Hüttl 2005 ; Marigo et al 2005 c; Steiner et al 2005 ; Beeson and MacMillan 2005 ), α-brominations (Bertelsen et al 2005 ), α-iodinations, and α-sulfenylations (Marigo et al 2005 a; Eqs 12–16) Once again, most of these reactions have never been realized before using... extremely rare Only very recently, Akiyama et al (2004 , 2005 a); also see Akiyama 2004 ; Akiyama et al 2005 b) and Terada et al (Uraguchi and Terada 2004 ; Uraguchi Scheme 10 Proline: a bifunctional catalyst New Concepts for Organocatalysis 15 Scheme 11 Phosphoric acid catalysis pioneered by Akiyama and Terada et al 2004 ; also see Uraguchi et al 2005 ; Terada et al 2005 ) demonstrated, in pioneering studies, that... Main, Germany Zeitler, K Institut für Organische Chemie, Universität Regensburg, Universitätsstr 31, 93053 Regensburg, Germany Ernst Schering Foundation Symposium Proceedings, Vol 2, pp 1–43 DOI 10.1007/2789 _2008 _084 © Springer-Verlag Berlin Heidelberg Published Online: 30 April 2008 New Concepts for Organocatalysis S.C Pan, B List(u) Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470... (Hoang et al 2003 ; Klussmann et al 2006 ) These lessons, as well as isotope incorporation studies, provided experimental support for our previously proposed single proline enamine mechanism and for Houk’s similar density functional theory (DFT)-model of the transition state of the intramolecular aldol reaction (List et al 2004 ; Bahmanyar and Houk 2001 a,b; Clemente and Houk 2004 ; Cheong and Houk 2004 ; Allemann... compounds In the year 2000 , we discovered a proline-catalyzed version of this powerful reaction (List 2000 ) Originally, ketones, aldehydes, and an aniline as the amine component were used in a catalytic asymmetric three-component reaction (Scheme 8; Eq 17) After our report, proline-catalyzed Mannich reactions with aldehydes as the donor were also developed (Córdova et al 2002 c; Hayashi et al 2003 b; Eqs 18,19) .