Intramolecular hydrogen bond-promoted Cndash;C bond formation: reaction rate enhancement and regioselective allylation of carbonyl compounds

摘要

R1 X O H R1 X OH SnR2 3 R3 R3 1 3 2 Solvent 3c A O O2N O H H O O2N O H SnBu3 SnBu3 OH O2N OH SnBu3 1c (2) Hydrolysis (1) ndash; SnBu3 (2) Hydrolysis (1) Intramolecular hydrogen bond-promoted Cndash;C bond formation: reaction rate enhancement and regioselective allylation of carbonyl compounds Hajime Ito, Yasuaki Ujita, Jun-ichi Tateiwa, Motohiro Sonoda and Akira Hosomi* Department of Chemistry and Graduate School of Chemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan. E-mail: hosomi@staff.chem.tsukuba.ac.jp Received (in Cambridge, UK) 15th September 1998, Accepted 6th October 1998 An intramolecular hydrogen bond promotes rate enhancement in both the allylation and the reduction of carbonyl compounds and also regioselective allylation.For the design of synthetic reactions, external catalysts or mediators are usually utilized for improving selectivity and mildness of reaction conditions.1 In the allylation reaction of carbonyl compounds with an allylmetal reagent such as an allylsilane or allyltin, Lewis and Broslash;nsted acid catalysts are often employed for this purpose.2ndash;4 Usually, the strong acidity of the Lewis or Broslash;nsted acid is needed to complete the reaction.However, the strong acid sometimes causes decomposition of both the allylmetal reagent and the substrate. In order to overcome this drawback, we have introduced an intramolecular hydrogen bond into the substrate to activate the substrate and to stabilize the transition state of the reaction.Although active arguments for the contribution of hydrogen bonds in the transition state of an enzymatic system have been presented, there are fewer reports on the utilization of the stabilization effect of the hydrogen bond in the transition state in Cndash;C bond formation between carbonyl compounds and organometallic reagents.5,6 To explore the synthetic utility of the hydrogen bond, we focused our attention on the features of the intramolecular hydrogen bond.Its moderate acidity and localization in a specific position in the substrate serve synthetic utility. Here we describe rate enhancement in the allylation and the reduction of a carbonyl group and the regioselective allylation promoted by an intramolecular hydrogen bond. There are numerous reports on the condensation reaction of an aldehyde with trialkylallyltin promoted by a Lewis or Broslash;nsted acid catalyst.3ndash;5 The thermal reactions of trialkylallyltin with carbonyl compounds at high temperature or high pressure have also been reported.In our first series of experiments, the activation effect of an intramolecular hydrogen bond in the nucleophilic reaction of organotin compounds was measured at low temperature without the addition of an acid catalyst (Table 1). Under THF reflux conditions without the addition of a Lewis acid, no adducts were observed for a mixture of tributylallyltin and benzaldehyde, which has no intramolecular hydrogen bond.Although salicylaldehyde 1a reveals a relatively strong intramolecular hydrogen bond between the hydroxy group and the oxygen atom in the carbonyl group, attempts to afford an allylation product were unsuccessful under the same conditions (entry 1). Introduction of an electron-withdrawing substituent para to the hydroxy group provided allylation product 3b in moderate yield (entry 2). A nitro group para to the hydroxy group was most efficient and gave products 3c,d in good yields even at room temperature (entries 3ndash;5).In entry 4, unreacted allyltin was recovered almost quantitatively. Next, in order to clarify the role of the hydroxy group in this reaction, we carried out experiments using carbonyl compounds 1d,e which have no hydrogen bond, and found that such substrates gave no adduct under the same conditions described above (entries 6 and 7). Addition of p-nitrophenol was not effective for the allylation Table 1 ortho Substituent effect in allylation reaction of carbonyl compoundsa Entry 1 X R1 R2 R3 T/deg;C 3 Yield () 1 1a H OH Bu H reflux 3a 0 2 1b Cl OH Bu H reflux 3b 49 3 1c NO2 OH Me H room temp. 3c 96 4 1c NO2 OH Bu H room temp. 3c 97 5b 1c NO2 OH Bu Me room temp. 3d quant. 6 1d NO2 H Bu Me room temp. 3e 0 7 1e NO2 OMe Bu Me room temp. 3f 0 8c 1d NO2 H Bu Me room temp. 3g 8 a A mixture of an aldehyde (0.5 mmol) and a trialkylallyltin (1.0 mmol) was stirred in THF (1.0 ml) for 48 h. b 1 equiv. of trialkylallyltin was used.c 4-Nitrophenol (1.0 equiv.) was added to the reaction. Scheme 1 Chem. Commun., 1998, 2443ndash;2444 2443R1 O2N O H R1 O2N HSnBu3 OH H H THF, room temp. 18ndash;24 h 1c R1 = OH d R1 = H e R1 = OMe 4a 92 b 18 c 12 R1 O H O H SnR2 3 R3 R1 OH O H R1 O H OH R3 R3 + 5 6 7 THF, 50 deg;C 48 h 2 (entry 8). These results clearly show that the hydroxy group of the substrate enhanced the reaction rate of the allylation. In view of the reaction mechanism, two paths are proposed for this rate enhancement (Scheme 1).The first one is that the intramolecular hydrogen bond directly promotes the allylation involving the stabilization of the transition state. In the second path, metalation of the hydroxy group first occurrs to give intermediate A. Another nucleophile attacks the carbonyl group of A activated by coordination to the internal stannyl group to give the product. The second path is not acceptable on the basis of the experimental result, namely, that 1 equiv.of tributylallyltin is sufficient to complete the reaction. The low reactivity of intermediate A, generated in situ by the reaction of 1c with tributyltin methoxide, also suggests the second path can be ruled out.7,8 These results indicate that the intramolecular hydrogen bond directly promoted the allylation reaction. The intramolecular hydrogen bond also mediates reduction of carbonyl compounds with tributyltin hydride (Scheme 2). Similar reactivity tendency was also observed in this case.The substrate having an intramolecular hydrogen bond gave reduced product 4a in good yield. The immobility of the proton in the hydrogen bond made possible regioselective reaction of a multi-functional compound. 9 An aldehyde which has two carbonyl groups was prepared to examine the selectivity of the allylation.10 The carbonyl group which is activated by the hydrogen bond was selectively allylated with tributylallyltin (Table 2). The selectivity was very high and minor product 7 was scarcely observed in these cases (entries 1 and 2).Substrates that have no hydrogen bond gave allylated products in poor yield (entries 3 and 4). These results show that an intramolecular hydrogen bond activates a particular functional group in the substrate selectively and stabilizes the transition state to enhance the reaction rate. In conclusion, a low-acidic intramolecular hydrogen bonding promotes nucleophilic reaction to a carbonyl group.Although the precise mechanism of these reactions involving a lowbarrier hydrogen bond (LBHB) is still unclear, this method offers a new tool in organic synthesis.6 Financial support for this work is partly provided by Grantsin- Aid for Scientific Research on Priority Areas from the Ministry of Education, Japan, and Pfizer Pharmaceuticals Inc. We thank Dow Corning Toray Silicone Co. Ltd., Chisso Co. Ltd. and Shin-Etsu Chemical Co. Ltd. for a gift of organosilicon compounds.Notes and references 1 S. Shambayati and S. L. Schreiber, in Comprehensive Organic Synthesis, ed. B. M. Trost, Pergamon, Oxford, 1991, vol. 1, pp. 283ndash;353. 2 A. Hosomi and H. Sakurai, Tetrahedron Lett., 1976, 1295. 3 S, Castellino and D. E. Volk, in Encyclopedia of Reagents for Organic Synthesis, ed. L. A. Paquette, Wiley, 1995, vol. 1, pp. 125ndash;128; Y. Yamamoto and N. Asao, Chem. Rev., 1993, 2207. 4 V. Gevorgyan, I. Kadota and Y. Yamamoto, Tetrahedron Lett., 1993, 34, 1313; S.E. Denmark, E. J. Weber, T. M. Wilson and T. M. Willson, Tetrahedron Lett., 1989, 45, 1053; A. Yanagisawa, M. Morodome, H. Nakashima and H. Yamamoto, Synlett, 1997, 1309: G. Kaur, K. Manju and S. Trehan, Chem. Commun., 1996, 581. 5 T. M. Cokley, P. J. Harvey, R. L. Marshall, A. McCluskey and D. J. Young, J. Org. Chem., 1997, 62, 1961; T. M. Cokley, R. L. Marshall, A. McCluskey and D. J. Young, Tetrahedron Lett. 1996, 37, 1905; N. Asao, A. Noriko, Z. Tan and K. Maruoka, Synlett, 1998, 377.After the submission of our paper, condensation reactions between more reactive tetraallyltin species and salicylaldehyde were reported. M. Yasuda, T. Fujibayashi and A. Baba, J. Org. Chem., 1998, 63, 6401. 6 W. W. Cleland and M. M. Kreevoy, Science, 1994, 264, 1887; G. A. Kumar and M. A. McAllister, J. Am. Chem. Soc., 1998, 120, 3159; E. L. Ash, J. L. Sudmeier, E. C. D. Fabo and W. W. Bachovchin, Science, 1997, 278, 1128. 7 After the addition of tributyltin methoxide and the removal of MeOH, the disappearance of 1c and the appearance of a new set of signals attributed to the quantitative formation of A was observed by NMR analysis: dH(270 MHz, CDCl3) 0.86 (t, J 7.3, 9H), 1.20ndash;1.65 (m, 18H), 8.18 (d, J 9.2, 1H), 8.20 (d, J 9.2, 3.0, 1H), 8.54 (d, J 3.0, 1H), 10.28 (s, 1H). 8 A reaction between A and allyltributyltin (1.3 equiv.) in THF for 48 h gave 3c (11) and 1c (82) at room temperature. 9 S. J. Angyal, P. J. Morris, J. R. Tetaz and J. G. Wilson, J. Chem. Soc., 1950, 2141. 10 Similar selectivity was achieved using a Lewis acid catalyst. T. Ooi, D. Uraguchi, N. Kagoshima and M. Maruoka, J. Am. Chem. Soc., 1998, 120, 5327. Communication 8/07172A Scheme 2 Table 2 Site selective allylation of carbonyl compounds using an intramolucular hydrogen bonda Entry 5 R1 R2 R3 Yield () Ratio 6:7 1 5a OH Bu H 95 50: 1 2b 5a OH Bu Me 99 50: 1 3 5b H Bu H 12 mdash; 4 5c OMe Bu H not found mdash; a A mixture of an aldehyde (0.5 mmol) and a trialkylallyltin (1.0 mmol) was stirred in dry THF (2.0 ml) at 50 deg;C for 48 h. b 5.0 ml of THF was used. 2444 Chem Commun., 1998, 2443ndash;2444