TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 13 (2002) 891–898 Pergamon Stereoselective oxazaborolidine–borane reduction of biphenyl alkyl ketones Giovanna Delogu, a, * Davide Fabbri, a Cristina de Candia, a Angela Patti b, * and Sonia Pedotti b a Istituto di Chimica Biomolecolare del CNR, Sez. di Sassari, Traversa la Crucca 3, regione Baldinca, Li Punti, 07040 Sassari, Italy b Istituto di Chimica Biomolecolare del CNR, Sez. di Catania, Via del Santuario 110, I -95028 Valverde CT, Italy Received 18 April 2002; accepted 29 April 2002 Abstract—Asymmetric reduction of three different biphenyl alkyl ketones with (R )-oxazaborolidine 1 as catalyst was successfully carried out and the corresponding biphenyl alcohols were obtained in high yield and e.e. High diastereoselectivity was achieved with the C 2 -symmetric, configurationally stable biphenyl 6 and more detailed investigations evidenced a cooperative effect between stereoaxis and stereocentre. © 2002 Elsevier Science Ltd. All rights reserved. 1. Introduction Enantiopure alkylaryl carbinols have received consider- able interest as building blocks for the preparation of chiral drugs and ligands by virtue of the hydroxyl group which can be further functionalised to afford amino, sulphur and phosphorus derivatives. 1 Asymmet- ric reduction of a carbonyl group is a direct route to chiral alcohols and in this context efficient reductive methods have been developed. 2–4 However, the effec- tiveness of the reduction process is dictated by the nature of the ketone and the choice of chiral ligand, thus, a reagent system with general applicability is not yet available. As part of an ongoing program on the preparation of hydroxylated biphenyls, 5 we focused our attention on the asymmetric reduction of functionalised prochiral biphenyl ketones catalysed by CBS–oxazaborolidine. The CBS method, developed by the groups of Itsuno 2a and Corey, 2c offers simplicity of procedure, high yields, high enantioselectivities and a wide range of applicabil- ity particularly with alkylaryl ketones. 6 Although ratio- nal modifications of the CBS catalyst structure allowed optimal enantioselectivity to be achieved for specific substrates, 7 the boron methyl derivative of oxazaboro- lidine of ,-diphenyl prolinol (CBS-Me) 1, is often the catalyst of choice due to its stability and commercial availability in both enantiomeric forms. To our knowledge, very little attention has been paid to the asymmetric reduction of biphenyl alkyl ketones via chemical 8 as well as enzymatic 9 methods and, in all examples, only configurationally flexible biphenyls have been reported. If the biphenyl ketone is configura- tionally stable, the stereogenic axis could be involved in the formation of the alcohol and different configura- tions at the biphenyl moiety can be envisaged for each prostereogenic centre. Enantiopure C 2 -symmetric biphenyl carbinols are valu- able intermediates in the preparation of new ligands 8b,10 and are also useful models for understanding the biosynthesis and stereochemistry of naturally occurring compounds which possess the biphenyl structure. 11 In the synthesis of lignin, the presence of dimeric neolig- nans e.g. 2 plays an important role in understanding the factors which govern the coupling and cross-coupling of the phenol units. 12 * Corresponding authors. E-mail: g.delogu@iatcapa.ss.cnr.it; patti@i ssn.ct.cnr.it 0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0957-4166(02)00210-0