Synthesis of Diversely Functionalised Dibenzylbutyrolactones and Aryltetralins from Silylated Cyanohydrin Anions Robert S. Ward,*a Andrew Pelter,a Antonella Brizzi,b Alessandro Segab and Paola Paolic aChemistry Department, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK bIstituto di Chimica Organica dell' Universita di Siena, Pian del Mantellini 44, 53100 Siena, Italy cDipartimento di Energetica, Universita degli Studi di Firenze, Via Santa Marta 3, 50139 Firenze, Italy The aryltetralins 7a and 7b and the keto-lactone 8 are synthesised by cyclisation and deprotection of the conjugate addition products 4a and 4b; the structure of 7b was unambiguously confirmed by an X-ray structural analysis.Following the methodology developed by Iwasaki et al.1�}3 we have shown that tandem conjugate addition by anions derived from tert-butyldimethylsilylcyanohydrins 1 to butenolides proceeds stereoselectively to give dibenzyl- butrolactones 2, which in turn a€ord access to aryltetralin lignans 3 (Scheme 1).4 In order to synthesise di€erentially protected lignans belonging to the dibenzylbutyrolactone and aryltetralin series we have now prepared the tandem conjugate addition product 4 and have examined its reactions with tri�Puoroacetic acid (TFA) and tetrabutyl- ammonium �Puoride (TBAF).The compounds produced are potential precursors for the biotechnological production of clinically important podophyllotoxin derivatives, and for investigation of the stereochemistry of the biosynthetic pathway.5�}7 The tert-butyldimethylsilylcyanohydrin 5 was synthesised in 3 steps from 3,4-dihydroxybenzaldehyde.Treatment of 5 with LDA followed by butenolide gave the adduct 6 in 80% yield as a 4:1 mixture of two diastereoisomers (Scheme 2). Treatment of the mixture with LDA followed by 4-tert- butyldimethylsilyloxy-3,5-dimethoxybenzaldehyde gave two products 4a (30%) and 4b (59%) which could be separated by column chromatography. Both 4a and 4b consisted of a mixture of two epimers which di€ered in their conRguration of the benzylic OH group.Cyclisation of 4a with TFA at 0 8C a€orded a single product 7a in 61% yield while cyclisation of 4b under the same conditions gave the C-4 epimer 7b in 58% yield, the structure of which was conRrmed by X-ray crystallography (Fig. 1). J. Chem. Research (S), 1998, 226�}227 J. Chem. Research (M), 1998, 1056�}1081 Scheme 1 Scheme 2 Fig. 1 X-Ray crystal structure of 7b (Ar a 4-tert-butyldimethylsilyloxy-3,5-dimethoxphenyl) *To receive any correspondence (e-mail: r.s.ward@swan.ac.uk). 226 J. CHEM. RESEARCH (S), 1998In a second series of experiments the tandem conjugate addition products 4a and 4b were treated with TBAF at 0 8C, with a view to regenerating the carbonyl group at C-6.In the event 4a or 4b gave the same fully desilylated compound 8 in 80¡À99% yield as a mixture of the two epimeric alcohols. In contrast, treatment of 4b with TBAF at ¡¦78 8C gave a mixture of two partially deprotected com- pounds 9 and 10, each as a mixture of epimeric alcohols.Further treatment of 9 with TBAF at 0 8C converted it into 8 (Scheme 3). Crystal data for 7b.DC42H67NO8Si3, Mr=798, F(000)= 864, triclinic, a= 7.183(4), b= 17.383(3), c =19.708(3) A �º , V=2409(2) A �º 3, = 81.52(1), = 83.34(4), = 84.21(4)8, space group P1, Z =2, Dx=1.101mg m¡¦3, l(Cu-K) = 1.54178 A �º . The X-ray data were collected using an Enraf- Nonius CAD-4 X-ray di€ractometer.Techniques used: 1H and 13C NMR, MS, IR, X-ray crystallography References: 13 Tables: 10 (1H and 13C NMR spectra of 4a, 4b, 6, 7a and 7b and X-ray data for 7b) Received, 23rd June 1997; Accepted, 20th January 1998 Paper E/7/04399F References cited in this synopsis 1 T. Ogiku, S. Yoshida, M. Takahashi, T. Kuroda, H. Ohmizu and T. Iwasaki, Tetrahedron Lett., 1992, 33, 4473, 4477. 2 T. Ogiku, S. Yoshida, T. Kuroda, M. Takahashi, H. Ohmizu and T. Iwasaki, Bull. Chem. Soc. Jpn, 1992, 65, 3495. 3 Y. Moritani, C. Fukushima, T. Ogiku, T. Ukita, T. Miyagishima and T. Iwasaki, Tetrahedron Lett., 1993, 34, 2787. 4 A. Pelter, R. S. Ward and N. P. Storer, Tetrahedron, 1994, 50, 10829. 5 J. P. Kutney, M. Arimoto, G. M. Hewitt, T. C. Jarvis and K. Sakata, Heterocycles, 1991, 32, 2305. 6 J. P. Kutney, Y. P. Chen, S. Gao, G. M. Hewitt, F. Furi-Brena, R. K. Milanova and N. M. Stoynov, Heterocycles, 1993, 36, 13. 7 J. P. Kutney, X. Du, R. Naidu, N. M. Stoynov and M. Takemoto, Heterocycles, 1996, 42, 479. Scheme 7a and 7b Scheme 3 J. CHEM. RESE