HETEROCYCLES

Communication | Special issue | Vol. 82, No. 2, 2011, pp. 1181-1187
Received, 6th September, 2010, Accepted, 4th October, 2010, Published online, 6th October, 2010.
DOI: 10.3987/COM-10-S(E)122

■ Asymmetric Synthesis of γ-Siloxyenamides via Chiral Auxiliary-Mediated Diastereoselective Coupling of Ynamides, Aldehydes, and Silane by Nickel Catalyst

Nozomi Saito, Tomoyuki Katayama, and Yoshihiro Sato*

Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

A nickel-catalyzed diastereoselective three-component coupling of optically active oxazolidinone-derived ynamides, aldehydes, and silane is described. The reaction proceeded via stereoselective formation of oxanickelacycle to give γ-siloxyenamide derivatives in a highly diastereoselective manner.

This paper is dedicated to Professor Albert Eschenmoser on the occasion of his 85th birthday.

Ynamides, electron-rich alkynes, show unique reactivity and have been recognized as versatile synthetic units in recent organic chemistry.1 Among the various reactions of ynamides, transformation of ynamides using transition metal catalysts has attracted much attention recently, and various excellent examples have been reported.1,2 In this context, we demonstrated nickel-catalyzed multicomponent coupling of oxazolidinone-derived ynamides 1, aldehydes 2, and silane 3 (Scheme 1).3 This reaction proceeded through oxanickelacycle I formed by oxidative addition of 1 and 2 to a zero-valent nickel complex to give γ-siloxyenamide derivative 4 in a highly regioselective manner.4 Herein we report asymmetric synthesis of γ-siloxyenamide derivatives via diastereoselective three-component coupling of ynamides having a chiral auxiliary, aldehydes and silane.5

First, the coupling reaction of phenylalanine-derived ynamide 5aa, aldehyde 2a and Et3SiH (3) was carried out in the presence of a Ni(0)-SIMes catalyst generated from Ni(cod)2, SIMes·HBF4 and KOtBu in situ in THF overnight (Table 1, run 1). As a result, the γ-siloxyenamide derivative 6aaa was obtained in 79% yield and with 66% de. Encouraged by these results, the effects of substituents on the oxazolidinone ring on the diastereoselectivity were examined (runs 2-6). The reaction of ynamide 5ba prepared from phenylglycine with 2a and Et3SiH (3) gave 6baa in 85% yield, 70% de (run 2). When ynamide 5ca having an isobutyl group on the oxazolidinone was reacted with 2a and 3, the diastereoselectivity was increased to 84% (run 3). Surprisingly, the reaction of alanine-derived ynamide 5da having the smallest methyl group on the oxazolidinone ring showed excellent diastereoselectivity, and the corresponding coupling product 6daa was obtained in 98% yield, 91% de (run 4). On the other hand, the reaction of ynamide derived from valine 5ea did not proceed probably due to the steric bulkiness of the isopropyl group (run 5). Moreover, when ynamide 5fa prepared from aminoindanol was employed, γ-siloxyenamide 6faa was obtained in 93% yield, 92% de (run 6).

All absolute configurations of the methyne carbon in the predominant diastereomer of the coupling products 6 were determined through derivation of 6daa, as shown in Scheme 2. Thus, treatment of the coupling product 6daa (91% de) with O3 gave α-hydroxyketone (+)-7, which was reduced by Zn(BH4)2 to give diol 8 as an inseparable mixture of diastereomers. The diol 8 was treated with 2,2-dimethoxypropane to give the corresponding acetonides cis-9 and trans-9 in 74% and 5% yields, respectively. After confirmation of the stereochemistry of cis-9 by NOE experiments, cis-9 was transformed into dibenzoate of 1-arylhexane-1,2-diol 10, whose absolute configurations were determined to be 1S and 2R-configurations by the CD exciton chirality method.6 Therefore, it was found that the major diastereomer in 6daa has an S-configuration at the methyne carbon. Furthermore, all other coupling products 6aaa-6caa and 6faa could be also converted into (+)-7 in a manner similar to that for 6daa. These result indicate that the predominant diastereomer of 6aaa-6caa and 6faa also has an S configuration at the methyne carbon.

Coupling reactions of various alanine-derived ynamides and aldehydes were investigated and the results are summarized in Table 2. The reaction of 5da and aromatic aldehydes 2b-d with Et3SiH (3) in the presence of a Ni(0)-SIMes catalyst afforded the coupling products 6dab-6dad in high yields and in high diastereoselectivity (runs 1-3). An aliphatic aldehyde 2e was also applicable to the coupling with 5da and 3, giving 6dae in 75% yield as a single diastereomer (run 4). On the other hand, ynamides 5db-5de having various substituents on the alkyne part were reacted with 2a and Et3SiH (3) by Ni(0)-SIMes to give the corresponding γ-siloxyenamides 6dba-6dea, respectively in good yields and in a highly diastereoselective manner (runs 5-8).7

It is well known that nickel-catalyzed reductive coupling of alkyne and aldehyde proceeds via the formation of oxanickelacycle generated by oxidative cycloaddition of alkyne and aldehyde to a zero-valent nickel complex.8,9 Moreover, Jamison and Houk recently reported that the oxidative cycloaddition is the rate-determining step of the alkyne-aldehyde coupling and controls the regioselectivity of formation of the oxanickelacycle.10 Therefore, the most significant step for the diasteroselection of this coupling of chiral ynamides and aldehydes was also thought to be the oxidative cycloaddition stage (Scheme 3). First, both the π-orbital of the triple bond and lone-pair electrons of the carbonyl group in ynamide 5, aldehyde 2 and ligand (SIMes) would coordinate to the nickel center, and two possible tetracoordinate complexes 11 and 12, in which the R1 group on the oxazolidinone ring should be oriented to avoid steric interaction with the bulky SIMes ligand, could be formed. Then oxidative cycloaddition from each tetracoordinate complex would occur to afford oxanickelacycle 13 or 14. However, the formation of 14 from 12 seems to be less favorable than the formation of 13 because of steric repulsion between the R3 group in the aldehyde and the bulky SIMes ligand. Thus, nickelacycle 13 would be formed preferably as compared with 14. Therefore, the coupling reaction would predominantly proceed via oxanickelacycle 13, and (S)-6 was obtained as a major diastereomer through σ-bond metathesis of 13 with Et3SiH (3) followed by reductive elimination. On the other hand, diastereoselectivity of the reaction of ynamides having a bulkier R1 group such as 5aa-5ca decreased in contrast to that of 5da having a methyl group as described above. It is thought that formation of 13 from 5aa-5ca might be less favorable than the reaction of 5da due to steric interaction between the hindered R1 group and the R3 group. Therefore, it is thought that contribution of the reaction pathway via 14 increased and the diastereoselectivity of the coupling diminished.

In summary, nickel-catalyzed three-component coupling of chiral oxazolidinone-derived ynamides, aldehydes and silane was developed. The reaction proceeds through the formation of oxanickelacycle to afford γ-siloxyenamide derivatives in a highly regio- and stereoselective manner.

ACKNOWLEDGEMENTS
This work was partly supported by a Grant-in-Aid for Science Research on Priority Areas (No. 19027005 and 20036005, Synergy of Elements) from MEXT, Japan and a Grant-in-Aid for Scientific Research (B) (No. 19390001) from JSPS. N.S. acknowledges the Akiyama Foundation and the Research Foundation for Pharmaceutical Sciences for financial support.

References

1. For recent reviews on chemistry of ynamides, see: (a) C. A. Zificsak, J. A. Mulder, R. P. Hsung, C. Rameshkumar, and L.-L. Wei, Tetrahedron, 2001, 57, 7575; CrossRef b) J. A. Mulder, K. C. M. Kurtz, and R. P. Hsung, Synlett, 2003, 1379; CrossRef (c) ‘Tetrahedron Symposia-in-Print No. 118’ ed. by R. P. Hsung, Tetrahedron, 2006, 62, 3781; CrossRef (d) G. Evano, A. Coste, and K. Jouvin, Angew. Chem. Int. Ed., 2010, 49, 2840; CrossRef (e) K. A. DeKorver, H. Li, A. G. Lohse, R. Hayashi, Z. Lu, Y. Zhang, and R. P. Hsung, Chem. Rev., 2010, 110, 5064. CrossRef
2. For our reports on transition metal catalysis based on ynamide as a platform, see: (a) N. Saito, Y. Sato, and M. Mori, Org. Lett., 2002, 4, 803; CrossRef (b) M. Mori, H. Wakamatsu, N. Saito, Y. Sato, R. Narita, Y. Sato, and R. Fujita, Tetrahedron, 2006, 62, 3872. CrossRef
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4. For recent examples of the preparation of γ-alkoxyenamide derivatives and their synthetic application, see: (a) H. McAlonan, J. P. Murphy, M. Nieuwenhuyzen, K. Reynolds, P. K. S. Sarma, P. J. Stevenson, and N. Thompson, J. Chem. Soc., Perkin Trans. 1, 2002, 69; CrossRef (b) P. M. Ylioja, A. D. Mosley, C. E. Charlot, and D. R. Carbery, Tetrahedron Lett., 2008, 49, 1111. CrossRef
5. For related works on reductive coupling reactions of ynamides and aldehydes using stoichiometric amounts of Ti complex, see: (a) R. Tanaka, S. Hirano, H. Urabe, and F. Sato, Org. Lett., 2003, 5, 67; CrossRef (b) S. Hirano, R. Tanaka, H. Urabe, and F. Sato, Org. Lett., 2004, 6, 727; CrossRef (c) S. Hirano, Y. Fukudome, R. Tanaka, F. Sato, and H. Urabe, Tetrahedron, 2006, 62, 3896. CrossRef
6. W. T. Wiesler and K. Nakanishi, J. Am. Chem. Soc., 1989, 111, 9205. CrossRef
7. Typical Procedure for the Nickel-Catalyzed Coupling of Ynamide, Aldehyde, and Et3SiH (Table 2, run 4). To a solution of Ni(cod)2 (14 mg, 0.050 mol), SIMes·HBF4 (20 mg, 0.050 mmol), and KOtBu (6.8 mg, 0.061 mmol) in THF (3.0 mL) were added 2e (0.16 mL, 1.5 mmol) and 3 (0.16 mL, 1.1 mmol) at 0 °C, and the mixture was stirred at the same temperature for 10 min. To the mixture was added a solution of 5da (91 mg, 0.50 mmol) in THF (2.0 mL) over a period of 7 h by a syringe pump at room temperature. After the slow addition was finished, the reaction mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was purified by flash column chromatography on silica gel (hexane/AcOEt = 8/1) to give 6dae (144 mg, 75%) as a colorless oil. [α]D26 -37.8° (c 0.22, CHCl3); IR (neat) 1761, 1236 cm-1; 1H NMR (500 MHz, CDCl3) δ 0.58-062 (m, 6H), 0.89 (d, J = 4.0 Hz, 3 H), 0.91 (d, J = 4.6 Hz, 3 H), 0.91 (d, J = 3.4 Hz, 3 H), 0.95 (t, J = 8.0 Hz, 9 H), 1.25 (d, J = 6.3 Hz, 3H), 1.29-1.45 (m, 6H), 1.69 (m, 1H), 1.99-2.9 (m, 2H), 3.94 (dd, J = 8.0, 5.2 Hz, 1H), 4.07 (m, 1H), 4.17 (dd, J = 8.0, 4.6 Hz, 1H), 4.44 (t, J = 8.3 Hz, 1H), 5.97 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 4.7, (3C), 6.8 (3C), 13.8, 18.5, 22.2, 23.0, 23.3, 24.1, 26.7, 30.4, 46.5, 52.4, 68.8, 73.2, 117.9, 139.2, 156.0; EI-LRMS m/z 354 [(M-Et)+], 326, 298, 251; EI-HRMS calcd for C19H36NO3Si [(M-Et)+] 354.2464, found 354.2458.
8. For nickel-catalyzed coupling of normal alkyne, aldehyde and silane via oxanickelacycle intermediate, see: (a) G. M. Mahandru, G. Liu, and J. Montgomery, J. Am. Chem. Soc., 2004, 126, 3698; CrossRef (b) K. Sa-ei and J. Montgomery, Org. Lett., 2006, 8, 4441; CrossRef (c) M. R. Chaulagain, G. J. Sormunen, and J. Montgomery, J. Am. Chem. Soc., 2007, 129, 9568; CrossRef For related nickel-catalyzed reductive coupling of alkyne and aldehyde in the presence of Et2Zn or Et3B as a reducing reagent, see: (d) E. Oblinger and J. Montgomery, J. Am. Chem. Soc., 1997, 119, 9065; CrossRef (e) W.-S. Huang, J. Chan, and T. F. Jamison, Org. Lett., 2000, 2, 4221. CrossRef
9. Recently, oxanickelacyclopentene from zero-valent nickel, aldehyde, and alkyne was isolated and its structure was elucidated by X-ray analysis. See: S. Ogoshi, T. Arai, M. Ohashi, and H. Kurosawa, Chem. Commun., 2008, 1347. CrossRef
10. P. R. McCarren, P. Liu, P. H.-Y. Cheong, T. F. Jamison, and K. N. Houk, J. Am. Chem. Soc., 2009, 131, 6654. CrossRef