TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 12 (2001) 1929–1937 Pergamon New bidentate chiral phosphoramidites in copper-catalyzed asymmetric 1,4-addition of diethylzinc to cyclic ,-enones: enantioselective tandem 1,4-addition-aldol reactions with 2-cyclopentenone Alessandro Mandoli, a,b Leggy A. Arnold, a Andre H. M. de Vries, a Piero Salvadori b and Ben L. Feringa a, * a Department of Organic and Molecular Inorganic Chemistry, Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands b Dipartimento di Chimica e Chimica Industriale, University of Pisa, V. Risorgimento 35, 56126 Pisa, Italy Received 10 July 2001; accepted 3 August 2001 Abstract—New bidentate phosphoramidites were prepared starting from ,,,-tetraphenyl-2,2-dimethyl-1,3-dioxolane-4,5- dimethanol (TADDOL) or 1,1-bi-2-naphthol (BINOL) and either 1,2-ethylene- or 1,3-propylenediamine N,N-disubstituted with achiral or chiral groups. The use of these ligands in the copper-catalyzed enantioselective conjugate addition of diethylzinc to 2-cyclohexenone and 2-cyclopentenone afforded products with e.e.s of up to 89 and 83%, respectively. © 2001 Elsevier Science Ltd. All rights reserved. 1. Introduction In recent years considerable progress has been achieved in the development of catalytic versions of the syntheti- cally important 1 enantioselective 1,4-addition of organometallic reagents to ,-unsaturated com- pounds, 2–4 especially in the case of the copper-mediated conjugate addition of organozinc reagents to enones. Among the different chiral ligands proposed for this purpose the phosphoramidites 1a, 1b and 1c, intro- duced by us, 5,6 have proven highly effective, with ligand 1a (Fig. 1) allowing virtually complete stereocontrol in the reaction of (functionalized) dialkylzinc R 2 Zn com- pounds with six-, seven- and eight-membered 2- cycloalkenones, 7 hence, opening a direct route to homochiral products containing cyclohexane and larger rings in their structure. 8 The addition of organozinc reagents to 2-cyclopentenone was more difficult to achieve. Surprisingly, the use of the BINOL derived phosphoramidite 1a resulted in very low diastereoselec- tivity (10% e.e.) 6,8a with this enone. On the other hand, cyclopenten-3,5-dione monoacetals, highly functional- ized 2-cyclopentenone derivatives, were successfully used (e.e.s of up to 97%) in the conjugate addition– aldol reaction with dialkylzincs in the presence of alde- hydes using ligand 1a. 9 Employing TADDOL-derived 10 ligands such as 2, we achieved e.e.s of up to 62%, in the presence of molecular sieves (MS), using 2-cyclopen- tenone as substrate. 11 Chan 12 obtained 89% e.e. in the 1,4-addition of diethylzinc to 2-cyclopentenone using the BINOL-based diphosphite 3, whereas Pfaltz 13 enhanced the enantioselectivity further to 94% using phosphite 4a containing a chiral oxazoline group. Recently Hoveyda 14 reported e.e. values of up to 97% using a chiral peptide-based phosphine ligand 4b in the catalytic 1,4-addition with diethylzinc to 2- cyclopentenone. In the continuing pursuit to develop effective ligands for the asymmetric conjugate addition to enones in particular 2-cyclopentenones and realizing that most of the phosphanes successfully employed in asymmetric catalysis are of the bidentate type, 15 we focussed on the screening of new bidentate phosphoramidites. In this respect, it is worth noting that early observations from our group demonstrated that Cu(I) can accommodate up to three monodentate ligands 1b 5 and further exper- imental evidence actually points to the presence of more than one ligand bound to the copper ion during the reaction. 16 In view of the present lack of detailed * Corresponding author. E-mail: feringa@chem.rug.nl 0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII:S0957-4166(01)00348-2