摘要:

PhCHO + PhNH2 + SnBu3 Ph NHPh Sc(OTf)3 SDS H2O room temp. R1CHO + R2NH2 + SnBu3 R1 NHR2 Sc(OTf)3 (0.2 equiv.) SDS (0.2 equiv.) H2O room temp. 20 h Sc(OTf)3-Catalyzed three-component reactions of aldehydes amines and allyltributylstannane in micellar systems. Facile synthesis of homoallylic amines in water Sh�u Kobayashi,* Tsuyoshi Busujima and Satoshi Nagayama Department of Applied Chemistry Faculty of Science Science University of Tokyo (SUT) and CREST Japan Science and Technology Corporation (JST) Kagurazaka Shinjuku-ku Tokyo 162 Japan Three-component reactions of aldehydes amines and allyltributylstannane proceeded smoothly in water without using any organic solvents in the presence of a small amount of scandium trifluoromethanesulfonate [Sc(OTf)3] and sodium dodecylsulfate (SDS) to afford the corresponding homoallylic amines in high yields.The reaction of imines with allyltributylstannane provides a useful route for the synthesis of homoallylic amines.1 The reaction is generally carried out in the presence of a Lewis acid in organic solvents under strict anhydrous conditions,2 because most imines Lewis acids and organotin reagents used are hygroscopic and easily decompose in the presence of even a small amount of water.3 On the other hand the utility of aqueous reactions is now generally recognized,4 and development of carbon–carbon bond-forming reactions that can be carried out in aqueous media is one of the most challenging tasks in organic synthesis. It was believed however that the above reaction would remain difficult to perform in water because of the use of water-sensitive imines Lewis acids and organotin reagents.Recently we have found that scandium trifluoromethanesulfonate [Sc(OTf)3]-catalyzed aldol reactions5 and allylations of aldehydes6 proceed smoothly in the presence of a small amount of a surfactant in water. It was indicated that micelles formed in these reactions and that the excellent hydrophobic reaction fields created realized the aqueous reactions. In the course of our investigations to develop new synthetic reactions in micellar systems we have found that three-component reactions of aldehydes amines and allyltributylstannane proceed smoothly in micellar systems using Sc(OTf)3 as a Lewis acid catalyst.† The reaction of benzaldehyde aniline and allyltributylstannane was chosen as a model and several sets of reaction conditions were examined.While the reaction proceeded sluggishly in the presence of Sc(OTf)3 without sodium dodecylsulfate (SDS) or in the presence of SDS without Sc(OTf)3 a 77% yield of the desired homoallylic amine was obtained in the presence of both Sc(OTf)3 and SDS. It was suggested that an imine formed from the aldehyde and the amine rapidly reacted with allyltributylstannane to afford the desired adduct. We also examined the effect of the amount of Sc(OTf)3 and SDS used and the results are summarized in Table 1. When a 70 mm SDS solution (0.4 equiv.) was used the desired homoallylic amine was obtained in a 79% yield and the yield remained unchanged with increasing amounts of SDS.‡ On the other hand it was found that reduction of the amount of Sc(OTf)3 decreased the yield and that a prolonged reaction time increased the yield.Finally a satisfactory yield was obtained when 0.2 equiv. Sc(OTf)3 and 35 mm (0.2 equiv.) SDS were used and the reaction was carried out at room temp. for 20 h. No homoallylic alcohol (an adduct between the aldehyde and allyltributylstannane) was produced under these conditions. Several examples of the present three-component reactions of aldehydes amines and allyltributylstannane are shown in Table 2. The reactions proceeded smoothly in water without using any organic solvents in the presence of a small amount of Sc(OTf)3 and SDS to afford the corresponding homoallylic amines in high yields. Not only aromatic aldehydes but also aliphatic unsaturated and heterocyclic aldehydes worked well. It is known that severe side reactions occur to decrease yields in the reactions of imines having a-protons with allyltributylstannane.1 It should be noted that aliphatic aldehydes especially non-branched aliphatic aldehydes reacted smoothly under these conditions to afford the homoallylic amines in high yields. In all cases no aldehyde adducts (homoallylic alcohols) were ob- Table 1 Effect of the amounts of Sc(OTf)3 and SDSa Sc(OTf)3/ mol% SDS/mm t/h Yield (%) 20 — 4 trace — 105b 4 trace 20 105 4 77 20 18 4 60 20 35 4 68 20 70 4 79 20 140 4 76 10 35 4 52 5 35 4 37 20 35 10 80 20 35 20 83 a PhCHO (1.3 equiv.) PhNH2 (1.0 equiv.) and allyltributylstannane (1.5 equiv.). b 0.6 equiv. Table 2 Three-component reactions of aldehydes amines and allyltributylstannane R1 R2 Yield (%) Ph Ph 83 Ph p-ClPh 90 Ph p-MeOPh 81 p-ClPh p-ClPh 70 2-Furyl p-ClPh 67 (71,a 82c) 2-Thienyl p-ClPh 67a (78c) Ph(CH2)2 p-ClPh 78 Me(CH2)7 p-ClPh 66 c-C6H11 Ph 80 (83b) c-C6H11 p-MeOPh 74 PhCO p-ClPh 71 (83c) (E)-PhCHNCH p-ClPh 80 (82a) a SDS 0.4 equiv.b 0.6 equiv. c 1.0 equiv. Chem. Commun. 1998 19 tained. It was suggested that the imine formation from aldehydes and amines was very fast in the presence of both Sc(OTf)3 and SDS,8 and that the selective activation of imines rather than aldehydes was achieved using Sc(OTf)3 as a catalyst.9 It is also noteworthy that using a small amount of a surfactant created efficient hydrophobic reaction fields10 and achieved the dehydration and addition reactions in water. A typical experimental procedure is as follows. To a 35 mm water solution of SDS (3 ml) and Sc(OTf)3 (0.1 mmol) were added the amine (0.5 mmol) allyltributylstannane (0.75 mmol) and the aldehyde (0.65 mmol) successively and the mixture was stirred at room temp.After 20 h the mixture was diluted with water and ethyl acetate and Amberlite IRA96SB was added. After being stirred for 10 min the resin was filtered and the filtrate was extracted with ethyl acetate. The combined organic layers were dried filtered and concentrated. The crude adduct was purified by column chromatography on silica gel to afford the pure desired homoallylic amine. In summary we have developed Sc(OTf)3-catalyzed threecomponent reactions between aldehydes amines and allyltributylstannane in micellar systems. The reactions proceed smoothly in water without using any organic solvents to afford the corresponding homoallylic amines in high yields.In addition to the synthetic utility of these reactions it should be noted that reactions using water-sensitive substrates have been successfully carried out in water under the present reaction conditions. Further progress is expected in this field and investigations on these micellar systems including mechanistic aspects are now underway in our laboratories. This work was partially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education Science Sports and Culture Japan and a SUT Special Grant for Research Promotion. S. N. thanks the JSPS fellowship for Japanese Junior Scientists. Footnotes and References * E-mail skobayas@ch.kagu.sut.ac.jp † We found that Sc(OTf)3 Y(OTf)3 and Ln(OTf)3 (Ln = La Ce Pr Nd Sm Eu Gd Tb Dy Ho Er Tm Yb Lu) are stable Lewis acids in water (ref.7). ‡ In some other substrates yields were improved a little with increasing amounts of SDS (see Table 2). 1 Review Y. Yamamoto and N. Asao Chem. Rev. 1992 93 2207. 2 G. E. Keck and E. J. Enholm J. Org. Chem. 1985 50 147; Y. Yamamoto T. Komatsu and K. Maruyama J. Org. Chem. 1985 50 3115; M. A. Ciufolini and G. O. Spencer J. Org. Chem. 1989 54 4739; C. Bellucci P. G. Cozzi and A. Umani-Ronchi Tetrahedron Lett. 1995 36 7289; M. Yasuda Y. Sugawa A. Yamamoto I. Shibata and A. Baba Tetrahedron Lett. 1996 37 5951. 3 Cf. P. A. Grieco and A. Bahsas J. Org. Chem. 1987 52 1378; H. Nakamura H. Iwama and Y. Yamomoto J. Am. Chem. Soc. 1996 118 6641. 4 C.-J. Li Chem. Rev. 1993 93 2023; A. Lubineau J. Ange and Y. Queneau Synthesis 1994 741; Structure and Reactivity in Aqueous Solution ed.C. J. Cramer and D. G. Truhlar ACS Washington DC 1994. 5 S. Kobayashi T. Wakabayashi S. Nagayama and H. Oyamada Tetrahedron Lett. 1997 38 4559. 6 S. Kobayashi T. Wakabayashi and H. Oyamada Chem. Lt. 1997 831. 7 S. Kobayashi Synlett 1994 689. 8 S. Kobayashi and H. Ishitani J. Chem. Soc. Chem. Commun. 1995 1379. 9 S. Kobayashi and S. Nagayama J. Org. Chem. 1997 62 232. 10 Cf. J. H. Fendler and E. J. Fendler Catalysis in Micellar and Macromolecular Systems Academic Press London 1975; Mixed Surfactant Systems ed. by P. M. Holland and D. N. Rubingh ACS Washington DC 1994; Surfactant-Enhanced Subsurface Remediation ed. by D. A. Sabatini R. C. Knox and J. H. Harwell ACS Washington DC 1995. Received in Cambridge UK 5th September 1997; 7/06489E 20 Chem. Commun. 1998

ISSN:1359-7345    

DOI:10.1039/a706498e

出版商:RSC    

年代:1998

数据来源: RSC