J. CHEM. SOC. PERKINTRANS. 1 1992 1081 Highly Regioselective 2 + 21 Photocycloaddition of Aromatic Aldehydes to Acetylf urans Howard A. J. Carless" and A. Frank E. Halfhide Department of Chemistry, Birkbeck College, Gorden House, 29 Gordon Square, London WCIH OPP, UK Stereospecific and highly regioselective oxetane formation occurs on irradiation of substituted aromatic aldehydes in the presence of 2-acetylfurans. The 2 + 2) cycloaddition of carbonyl compounds to furan to yield bicyclic oxetanes (e.g. 1 in Scheme 1)' is an efficient photochemical process. This PaternbBuchi reaction has been 1 R1=R2=Ph 2 R1= H, R2 = Ph scheme 1 exploited in synthetic with success particularly by Schreiber and his group.4 The bicyclic oxetanes which result from photocycloaddition can be transformed by ring opening at the strained acetal carbon.' Alternatively, the dihydrofuran ring can be selectively manipulated, as in the recent photo- chemical synthesis of oxetanocin, 3,6 a nucleoside with anti- viral activity against HIV.The recent discovery of other oxetanes with significant anti-viral properties' makes 2 + 2) photocycloaddition a route of potential importance. CH,OH 3 The photocycloaddition of aldehydes to furans shows excellent stereoselectivity (95) in forming the em-adduct (e.g.2),' but does suffer from one disadvantage: in the attack on an unsymmetrically substituted furan, the reaction shows little regioselectivity. Attack of photoexcited benzaldehyde on 2-methylfuran, for example, gives the two adducts 4a and 5a in a 1.3:1 ratio4e (Table 1).Although the adducts are difficult to separate, the greater reactivity of the bridgehead-substituted isomer 4a can lead to its selective destruction on silica gel as a means of separation.6 Schreiber has attempted to overcome this problem by the use of a bulky trialkylsilyl or trialkylstannyl group at the 2-position of the furan ring, when improved regioselectivitiesof up to 20: 1 can be obtained for attack at the unsubstituted double bond of the furan (Table 1, entries 2, 3),4e yielding dominantly 5. We now report that aromatic aldehydes undergo a remarkably selective photocycloaddition to 2-acetylfurans, with bicyclic oxetane formation occurring at the more substituted furan double bond, to give 4.Our initial investigations showed that the regioselectivity of photocycloaddition of aromatic aldehydes to alkylfurans and furfuryl alcohols or their derivatives was indeed low (Table 1, entries 4-7). For 3-substituted furans or unsymmetrical 2,5- 6 7 Ac 8 9 Fig. 1 Relative amounts of cycloaddition products formed by attack of photoexcited aromatic aldehydes on substituted furans: 6 and 7, benzaldehyde; 8,2-chloro- or 4-cyano-benzaldehyde; 9, 3-flUOrO- (ratio 5.3), 4-methoxycarbonyl-(ratio3.3) or Qcyano-benzaldehyde (ratio 2.3) disubstituted furans, this lack of selectivity was also evident. Fig. 1 shows the relative amounts of cycloaddition products which resulted from attack of benzaldehyde at each double bond of the substituted furans 6 and 7.However, photolysis of a benzene solution of 4-cyanobenzaldehyde and 2-acetylfuran led to a single major adduct, 4b, isolated by column chrom- atography in 70 yield. Proton NMR spectroscopy of the crude photolysate showed that the regioselectivity of the reaction was at least 20:l in favour of attack at the acetyl- bearing double bond; we were unable to detect the alternative regioisomer 5b.A similar selectivity of attack was found using 4-methoxycarbonylbenzaldehydeor terephthaldehyde as the carbonyl components, which gave 4cand 4d in good yield (65-80)(Table 1, entries 8-10). High regioselectivity ( 10: 1) was also observed for photocycloaddition of 2-chlorobenzaldehyde or 4-cyanobenz- aldehyde to 2-acetyl-Smethylfuran 8 (Fig.1). Interestingly, 3-acetylfurans such as 9 also underwent photocycloaddition to aromatic aldehydes (3-flUOrO-, 4-methoxycarbonyl- or 4-cyano- benzaldehyde), but with the reduced selectivity shown in Fig. 1. In these last mentioned examples, adducts corresponding to cycloaddition at the 2,3- and 4,S-double bonds of the furan were easily separated and identified by 'H and 13C NMR spectroscopy. The notable regioselectivity for attack by excited aldehyde on the more substituted double bond of these furans having electron-withdrawing groups was also found for attack 1082 J. CHEM. SOC. PERKIN TRANS. I 1992 Table 1 Regioisomeric oxetanes produced by photocycloaddition of 2-substituted furans to aromatic aldehydes Entry 2-Substituted furan Aldehyde ArCHO Ratio 4:5 Ref.1 R = Me Ar = Ph 1.3: 1 a 2 R = SiMe, Ar = Ph 1:2.5 a 3 R = SiPrlsquo;, Ar = Ph 1:20 a 4 5 R = CH,OH R = CH,OSiBulsquo;Me, Ar = Ph Ar = Ph 1.5: 1 1:1.1 b b 6 7 R = Me R = Me Ar = 2-Fury1 Ar = 4-CNCGH4 1:l 1:2 b b 8 R = AC Ar = 4-CNC,H4 20: 1 b 9 R = AC Ar = 4-MeO,CC,H4 20: 1 b 10 R = AC Ar = 4-CHOC6H4 20: 1 b 11 R = CN Ar = 3-FC6H4 10:1 b a Ref. 4e. This work. on 2-cyanofuran (Table 1, entry ll), but competitive References polymerisation of the furan reduced the yield of oxetane 4e to 1 G. 0.Schenck, W. Hartmann and R. Steinmetz, Chem. Ber., 1963,, ca.10 in this case. 498. Curiously, although the photocycloadditions were successful 2 G.Jones, 11, Org. Photochem., 1981,5, 1. with electron-withdrawing substituted aromatic aldehydes or 3 H. A. J. Carless, in Synthetic Organic Photochemistry, ed. W. M. Horspool, Plenum Press, New York, 1984, p. 425. even 2-furaldehyde, they were very slow or not observed for 4 (a) S. L. Schreiber, Science, 1985, 227, 857; (b) threo aldols: S. L. electron-donating substituted examples (e.g. 4-methoxybenz- Schreiber, A. H. Hoveyda and H.-J. Wu, J.Am. Chem. Soc., 1983,105, aldehyde) or benzaldehyde itself. This may possibly be a 660; (c) (+)-asteltoxin: S. L. Schreiber and K. Satake, J. Am. Chem. consequence of triplet energy transfer from the latter (higher Soc., 1984,106,4186; (d)(+)-avenaciolide: S. L. Schreiber and A.H. Hoveyda, J. Am. Chem. SOC., 1984, 106, 7200, (e) kadsurenone-energy) triplet donors to the acetylfuran acceptor^.^ However, a ginkgolide hybrid: S. L. Schreiber, D. Desmaele and J. A. Porco, Jr.,newly found method for metallation of the bicyclic oxetanesrdquo; Tetrahedron Lett., 1988,29,6689.could extend the synthetic usefulness of these adducts. 5 A. Zamojski and T. Koiluk, J. Org. Chem., 1977,42, 1089; S. Jarosz and A. Zamojski, J. Org. Chem., 1979,44,3720. 6 R. Hambalek and G. Just, TerrahedronLett., 1990,31,5445; for other examples of dihydrofuran functionalisation, see R. Hambalek and G.Experimental Just, Tetrahedron Lett., 1990,31,4693.Synthesis of exo- 1 -Acetyl-6-(4rsquo;-cyanophenyl)-2,7-dioxabi-7 Y. Wang, G. W. J. Fleet, R. Storer, P.L.Myers, C. J. Wallis, 0.cyclo3.2.0Jhept-3-ene 4b.-A solution of 4-cyanobenzaldehyde Doherty, D. J. Watkin, K. Vogt, D. R. Witty, F. X.Wilson and J. M. (1.0 g, 7.6 mmol) and 2-acetylfuran (2.66 g, 24 mmol) in benzene Peach, Tetrahedron: Asymmetry, 1990, 1, 527; C. 0-Yang, W. Kurz, (85 cm3) in the presence of sodium carbonate (0.1 g) under E. M. Eugui, M. J. McRoberts, J. P. H. Verheyden, L. J. Kurz and nitrogen was irradiated for 4 h, using a 450 W Hanovia K. A. M. Walker, Tetrahedron Lett., 1992,33,41. medium-pressure mercury arc and Pyrex glassware. Evapor- 8 A. G. Griesbeck and S. Stadtmiiller, Chem. Ber., 1990,123,357; A. G. ation and chromatography of the residue on silica gel, eluting Griesbeck, H. Mauder, K. Peters, E.-M. Peters and H. G. von Schnering, Chem. Ber., 1991,124,407.with 10 acetone-90 light petroleum (b.p. 40-60 OC-0.03 9 D. R. Arnold, Adv. Photochem., 1968,6,301.triethylamine, gave the adduct 4b (70); 6,(270 MHz; 10 S. L. Schreiber and J. A. Porco, Jr., J. Org. Chem., 1989,54,4721. CDCl,) 7.68 (2 H, d, J 8.6,3rsquo;-H and 5rsquo;-H), 7.47 (2 H, d, J 8.6,2rsquo;-Hand6rsquo;-H),6.72(1 H,dd,J2.7and1.2,3-H),5.64(lH,d,J3.5, 6-H),5.53(1H,t,Jca.3,4-H),3.92(1H,dt,J1.2,ca.3andca.3, 5-H) and 2.33 (3 H, s, CH,CO); 6,(67.9 MHz; CDC1,) 198.5 (CO), 149.0 (C-3), 144.4 (C-1rsquo;), 132.6 (C-2rsquo; and C-6rsquo;), 126.1 Paper 2/01 148D (C-3rsquo; and C-57, 118.5 (CN), 113.7 (C-l), 112.3 (C-47, 104.6 Received 3rd March 1992 (C-4), 89.8 (C-6), 51.4 (C-5) and 23.7 (CH,). Accepted 3rd March 1992
展开▼
