Cascade Macrocyclisation - Transannulation Reactions. - In some of our first investigations, we examined the radical macrocyclisation - transannulation sequence involving the iodotrienone 5, with a view to a 'one-pot' synthesis of 1-decalone. Earlier work, based on the precedent set by the studies of Porter et al, had demonstrated the need for an electron deficient alkene electrophore, e.g. a conjugated enone, to promote macrocyclisations with nucleophilic radical centres. Thus, when a solution of 5 in benzene was heated in the presence of 1.1 equivs of Bu3SnH and a catalytic amount of AIBN for 0.5 h, workup and chromatography gave a 2:3 mixture of the cis-isomer 6 and trans-isomer 7 of 1-decalone, in a combined yield of 72%; treatment of this mixture with DBU (25°C, 24 hr) allowed the isolation of trans-1-decalone in essentially quantitative yield (Scheme 2).
In further investigations of the scope for sequential radical macrocylisation - transannulations in bicycle constructions we showed that whereas the iodo-dienone 11 underwent tandem 9-endo-5-exo cyclisation producing the cis-tetralone 12 in reasonable yields (~50%), the corresponding E-octadienone 13 led only to the Z-cyclooctenone 14, and the iododienone 16 led to the 4-cyclopentyl substituted cyclohexanone (17; 95%), ie not to the anticipated 7,6-bicyclic ketone 15, on treatment with Bu3SnH-AIBN.
Sequential 6-Endo Trigonal Cyclisations. - It is now thirty years since Breslow et al, and later Julia et al first examined the possibility of a free-radical mechanism for the oxidative cyclisation of squalene, and more recently this hypothesis has been re-visited by Snider et al and by Zoretic et al amongst others. The construction of fused polycycles by way of sequential radical mediated cyclisation reactions from alkyl centred radicals is well documented. Furthermore, with few exceptions 5-exo trig cyclisations are generally preferred over 6-endo trig closures from hex-5-en-1-yl radical intermediates, and attempts to use consecutive 6-endo trig cyclisations from (5-, 9-, 13-) polyolefinic alkyl radical precursors in the formation of linear and angular 6-ring fused constructions have met with failure. The unusual tendency of hex-5-en-oyl, i.e. acyl, radicals to cyclise via the 6-endo trig mode, leading to six-ring carbocycles, has prompted us to evaluate the consecutive cyclisations of a range of (5-, 9-, 13-, 17-) polyolefinic acyl radical intermediates with a view to the synthesis of linear and angular fused 6-ring systems include steroid constructions. We chose phenylselenyl esters as the most practical and convenient source of acyl radical intermediates.
We first examined the cyclisations of the acyl radical intermediates produced from the Z- and E-isomers of the diene selenyl ester 34. When solutions of the pure Z- and E-isomers of 34 were treated separately with Bu3SnH-AIBN (reflux 8 h), each was found to undergo two consecutive 6-endo trig cyclisations leading to the trans-decalone 37 in 70-80% yield. The formation of a single diastereoisomer of a single regioisomer of 37 from either the Z- or E-isomer of 34 is significant, and is best rationalised on the basis of: i, rapid inversion of the stereochemistry of the beta-keto radical intermediate (35 to 36) prior to the second ring forming reaction, and ii, preference for formation of the most stable radical product in the second 6-endo cyclisation leading to 37 from 36. The importance of substitution on the 5- and the 9- double bonds in 34 in determining the regiochemical outcome of the bi-cyclisation leading to 37, was demonstrated by cyclisations of the related phenyl selenyl esters 38, 39 and 40, to 41, 42 and 43 respectively.
 For recent reviews see: J.K. Sutherland "Polyene Cyclisations", in Comprehensive Organic Synthesis, Vol 3, 341, Ed. B.W. Trost, Pergamon Press, 1991; S.K. Taylor, Org. Prep. Proc. Int., 1992, 24, 247.
 e.g. N.E. Carpenter, D.J. Kucera and L.E. Overman, J. Org. Chem., 1989, 54, 5846; A. de Meijere, F.E. Meyer and P.J. Parsons, J. Org. Chem., 1991, 56, 6487; M.J. Dorrity, R. Grigg, J.F. Malone, V. Sridharan and S. Sukirthalingham, Tetrahedron Lett., 1990, 31, 1343; Y. Shi and B.M. Trost, J. Am. Chem. Soc., 1992, 114, 791.
 e.g. P. Deslonghcamps, Aldrichim Acta, 1991, 24, 43.
 For bibliography see: W.B. Motherwell and D. Crich, Free Radical Chain Reactions in Organic Synthesis, Academic Press, London, 1991; C.P. Jasperse, D.P. Curran and T.L. Fevig, Chem. Rev., 1991, 91, 1237.
 N.J.G. Cox, G. Pattenden and S.D. Mills, Tetrahedron Lett., 1989, 30, 621; N.J.G. Cox, S.D. Mills and G. Pattenden, J. Chem. Soc., Perkin Trans. 1, 1992, 1313; S.A. Hitchcock and G. Pattenden, Tetrahedron Lett., 1990, 31, 3641; S.A. Hitchcock and G. Pattenden, J. Chem. Soc., Perkin Trans. 1, 1992, 1323.
 See for example: A.Ali, D.C. Harrowven and G. Pattenden, Tetrahedron Lett., 1992, 33, 2851; G. Pattenden and S.J. Reynolds, J. Chem. Soc., Perkin Trans. 1, 1994, 379.
 G. Pattenden, A.J. Smithies and D. S. Walter, Tetrahedron Lett, 1994, 35, 2413.
 G.J. Hollingworth, G. Pattenden and D. J. Schulz, Aust. J. Chem., 1995, 48, 381.
 For recent reference and bibliography see: P.V. Fish, A.R. Sudhakar and W.S. Johnson, Tetrahedron Lett., 1993, 34, 7849.
 G. Pattenden and S.J. Teague, Tetrahedron Lett., 1984, 25, 3021; Tetrahedron, 1987, 43, 5637.
 For some preliminary results see reference 7.
 For some summary of earlier work see: G. Pattenden, 'Polycycle Constructions by Transition Metal Catalysed and Radical Mediated Processes' in Organometallic Reagents in Organic Synthesis, Academic Press, eds. J.H. Bateson and M.B. Mitchell, 1993.
 See: N.A. Porter, D.R. Magnin and B.T. Wright, J. Am. Chem. Soc., 1986, 108, 2787; N.A. Porter, V.H.-T. Chang, D.R. Magnin and B.T. Wright, J. Am. Chem. Soc., 1988, 110, 3554; N.A. Porter, B. Lacher, V.H.-T. Chang and D.R. Magnin, J. Am. Chem. Soc., 1989, 111, 8309.
 S.A. Hitchcock and G. Pattenden, Tetrahedron Lett., 1992, 33, 4843 (corrigendum Tetrahedron Lett., 1992, 33, 7448).
 D.W. Pryde, Unpublished work; Nottingham University.
 For some preliminary results see: M.J Begley, G. Pattenden, A.J. Smithies and D.S. Walter, Tetrahedron Lett., 1994, 35, 2417.
 For an example of a radical-mediated transannular strategy towards diterpenoid ring systems see: A.G. Myers, K.R. Condronski, J. Am. Chem. Soc., 1993, 115, 7926; idem, ibid, 1995, 117, 3057.
 A.L.J. Beckwith and C.H. Schiesser, Tetrahedron, 1985, 41, 3925; K.N. Houk and D.C. Spellmeyer, J. Org. Chem., 1987, 52, 959; K.N. Houk and J.L. Broeker, J. Org. Chem., 1991, 56, 3651.
 R. Breslow, E. Barrett and E. Mohacsi, Tetrahedron Lett., 1962, 1207; R. Breslow, S.S. Olin and J.T. Groves, Tetrahedron Lett., 1968, 1837.
 M. Julia, Tetrahedron Lett., 1973, 4464.
 M.A. Dombroski, S.A. Kates and B.B. Snider, J. Am. Chem. Soc., 1990, 112, 2759.
 P.A, Zoretic, X. Wang and M.L. Caspar, Tetrahedron Lett., 1991, 32, 4819; P.A. Zoretic, Z. Shen, M. Wang and A.A. Ribeiro, Tetrahedron Lett., 1995, 36, 2925; P.A. Zoretic, Y. Zhang, and A.A. Ribeiro, Tetrahedron Lett., 1995, 36, 2929.
 e.g. M. Hoffman, Y. Gao, B. Pandey, S. Klinge, K.D. Warzecha, C. Kruger, H.D. Roth and M. Demuth, J. Am. Chem. Soc., 1993, 115, 10358.
 D.C. Spellmeyer and K.N. Houk, J. Org. Chem., 1987, 52, 959; A.L.J. Beckwith, Tetrahedron, 1981, 37, 3073; A.L.J. Beckwith and C.H. Schiesser, Tetrahedron, 1985, 41, 3925; D.P. Curran, Synthesis, 1988, 417; D.P. Curran, Synthesis, 1988, 489; M. Julia, Acc. Chem. Res., 1971, 4, 386.
 cf. E.R. Lee, I. Lakomy, P. Bigler and R. Scheffold, Helv. Chim. Acta., 1991, 74, 146.
 D.J. Coveney, V.F. Patel, G. Pattenden and D.M. Thompson, J. Chem. Soc., Perkin Trans. 1, 1990, 2721; T.M. Patrick, Jr., J. Org. Chem., 1952, 17, 1009, 1269; R. Dulou, Y. Chretien-Bessiere and H. Desalbres, C.R. Acad. Sci., Ser. C, 1964, 258, 603; J-P. Montheard, ibid., 1965, 260, 577; M. Chatzopoulos and J-P. Montheard, ibid., 1975, 280, 29; J.A. Kampmeier, S.H. Harris and D.K. Wedegaertner, J. Org. Chem., 1980, 45, 315; M. Julia and M. Maumy, Bull. Soc. Chim. Fr., 1969, 2415; Z. Cekovic, Tetrahedron Lett., 1972, 749; E.J. Walsh, Jr., J.M. Messinger II, D.A. Grudoski and C.A. Allchin, Tetrahedron Lett., 1980, 21, 4409; P. Delduc, C. Tailham and S.Z. Zard, J. Chem. Soc., Chem. Comm., 1988, 308; D.L. Boger and R.J. Mathvink, J. Org. Chem., 1988, 53, 3377; D.L. Boger and R.J. Mathvink, J. Org. Chem., 1989, 54, 1779; D.L. Boger and R.J. Mathvink, J. Am. Chem. Soc., 1990, 112, 4003; D.L. Boger and R.J. Mathvink, J. Am. Chem. Soc., 1990, 112, 4008; D.L. Boger and R.J. Mathvink, J. Org. Chem., 1990, 55, 5442; D.L. Boger and R.J. Mathvink, J. Org. Chem., 1992, 57, 1429; D. Crich and S.M. Fortt, Tetrahedron Lett., 1987, 28, 2895; D.Crich and S.M. Fortt, Tetrahedron Lett., 1988, 29, 2585; D. Crich and S.M. Fortt, Tetrahedron, 1989, 45, 6581; D. Crich, K.A. Eustace and T.J. Ritchie, Heterocycles, 1989, 28, 67; D. Batty, D. Crich and S.M. Fortt, J. Chem. Soc., Chem. Commun., 1989, 1366; f) D. Batty, D. Crich and S.M. Fortt, J. Chem. Soc., Perkin Trans., 1, 1990, 2875; D. Crich, K.A. Eustace, S.M. Fortt and T.J. Ritchie, Tetrahedron, 1990, 46, 2135; D. Batty, D. Crich, Tetrahedron Lett., 1992, 33, 875.
 Both Boger et al and Crich et al have also examined aspects of tandem cyclisations of acyl radicals produced from certain unsaturated selenyl esters. See under reference 26.
 For preliminary results see: a) L. Chen, G.B. Gill and G. Pattenden, Tetrahedron Lett., 1994, 35, 2593. b) H. Simonian, Unpublished work; Nottingham University.