J. Org. Chem. 1995,60,2322-2323
2322
Intramolecular Michael Additions: CopperU) Chloride-Mediated Conjugate Addition of Vinyltrimethylstannane Functions to a#-Unsaturated Ketones Edward Piers,* Ernest J. McEachern, and Patricia A. Burns Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, Canada V6T 1Z1 Received January 6, 1995
The intramolecular conjugate addition of stabilized carbanionic centers to Michael acceptor functions is a well established process that exhibits a good deal of synthetic utility.lI2 In contrast, reports of methods that entail intramolecular Michael additions of nonstabilized carbanionic functions (e.g., organometallic species)to carboncarbon double bonds activated by an electron-withdrawing group are relatively rare. In this regard, the work of Wender,3C ~ o k eCurran: ,~ Kocovsky,G and Danheiser' should be cited. Collectively, a large majority of the reactions reported by these research groups have involved the organometallic-mediated conjugate addition of primary alkyl functions to a variety of Michael acceptors. Only the publications of Wender and Cooke describe conjugate addition of unsaturated (alken~l,3~9~" aryl3b) moieties. Clearly, an effective process for the intramolecular, organometallic-mediated Michael addition of substituted alkenyl groups to enone functions would be a valuable addition to the arsenal of methods that effect the synthesis of usefully functionalized carbocycles. A recent reportSafrom this laboratory disclosed that efficient stereospecific intramolecular cross couplings of vinyltrimethylstannane and alkenyl halide functions can be effected by treatment of the requisite substrates with copper(I) chloride. Separate control experiments8bhave
a
0
shown that this coupling process is initiated by interaction of the copper(1) salt with the vinylstannane function, and it is reasonable to conclude that a vinylcopper(1) species is formed as an inte~mediate.~ Consequently, we decided to investigate the possibility of carrying out intramolecular conjugate additions of alkenyl functions to a$-unsaturated ketones via a protocol portrayed in general terms by the conversion of 1 into 2 (eq 1). We report herein that this new (proposed)process can indeed be put into practice.1° (1)Jung, M. E. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, U.K., 1991; Vol. 4, Semmelhack, M. E., Ed., pp 24-30. (2) Permutter, P. Conjugate Addition Reactions in Organic Synthesis; Pergamon Press: Oxford, U.K., 1992. (3) (a) Wender, P. A,; Eck, S. L. Tetrahedron Lett. 1977, 1245. (b) Wender, P. A.; White, A. W. J . Am. Chem. Soc. 1988, 110, 2218. (4) (a) Cooke, M. P., Jr.; Widener, R. K. J . Org. Chem. 1987, 52, 1381. (b) Cooke, M. P., Jr. J . Org. Chem. 1993,58,6833and references cited therein. (5) Curran, D. P.; Wolin, R. L. Synlett 1991, 317.
The substituted 2-cyclohexen-1-ones 7-12employed in a part of this study were prepared as shown in Scheme 1. Alkylation of the enone 311 with (Zbl-bromo-3(trimethylstannyl)-2-butene(19)12provided the keto stannane 413in excellent yield. Subjection of 4 to further alkylation (MeI) or to methoxy~arbonylation~~ gave the intermediates 5 and 6 , respectively. Reaction of the ketone 4 with each of the reagents diisobutylaluminum hydride, MeMgBr, and EtMgBr, followed by acid-catalyzed hydrolysis of each of the resultant products under carefully defined conditions, produced the required substrates 7-9. In similar fashion, compound 5 was readily transformed into the enones 10 and 11, while the keto ester 6 was converted into the corresponding enone 12. Using reactions similar to those summarized in Scheme 1, the ketone 2015was employed as a precursor to the substituted 2-cyclopenten-1-onesubstrates 23 and 24 (see Scheme 2). Although alkylation of 20 with the allylic bromide 19 gave 21 in rather poor yield (40%, unoptimized), subsequent methylation of 21 to afford 22 was efficient (79% yield). Reduction of 21 and 22 and subsequent acid-promoted hydrolysis-dehydration of the resultant crude products provided the corresponding enones 23 and 24 (79 and 83% yield, respectively). Treatment of compound 7 with 2.5 equiv of copper(1) chloride16 in dry DMF at room temperature resulted in the facile, highly efficient formation of the cis-fused bicyclo[4.3.0lnonenone 1317(96%yield, Scheme 1,Table 1, entry 1). When 1 equiv of CuCl was employed, the reaction proceeded at a reasonable rate until approximately 50% conversion and then became very sluggish. On the other hand, use of 2 equiv of CuCl gave a result very similar to that recorded in Table 1, entry 1. For the sake of convenience and consistency, we have routinely carried out our experiments with 2.5 equiv of the copper(1) source. Subjection of the cyclohexenone substrates 8-12 to CuC1-mediated cyclization reactions produced the corresponding bicyclic products 14-18(Scheme 1).The results of these experiments are summarized in Table 1(entries 2-8). Most of these transformations were found to be very efficient. However, the conversion of substrate 9 into 15 (entry 3) was low-yielding, and the expected (6) Kocovsky, P.; Srogl, J . J . Org. Chem. 1992, 57, 4565. (7) Bronk, B. S.; Lippard, S. J.; Danheiser, R. L. Organometallics 1993,12, 3340. (8) (a) Piers, E.; Wong, T. J . Org. Chem. 1993, 58, 3609. (b) Piers,
E.; Wong, T. Unpublished work. (9) For a recent interesting study on the effect of copper(1) iodide on Pd(O)-catalyzed cross coupling of vinylstannanes with alkenyl halides or triflates, see: Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind, L. S. J . Org. Chem. 1994, 59, 5905. (10) For a report describing the intermolecular CuC1-promoted addition of vinyltributylstannanes to substituted allenecarboxylates, see: Tanaka, H.; Kameyama, Y.; Sumida, S.; Torii, S. TetrahedronLett. 1992, 33, 7029. (11) Panouse, J.; SaniB, C. Bull. Soc. Chim. Fr. 1956, 1272. (12)This reagent was prepared in 68% yield from ethyl (22-3-
(trimethylstannyl)-2-butenoate (Piers, E.; Chong, J. M.; Morton, H. E. Tetrahedron 1989,45,363) via a two-step sequence: reduction (i-BuzAlH, CHZC12,O "C) and reaction of the resultant alcohol with PhaP*Brz in CHZC12 (0 "C) in the presence of imidazole. (13) New compounds reported herein were spectrally characterized and gave satisfactory elemental (C, H) analyses and molecular mass determinations (high-resolution mass spectrometry). (14) Mander, L. N.; Sethi, S. P. Tetrahedron Lett. 1983, 24, 5425. (15)Koreeda, M.; Liang, Y.; Akagi, H. J. Chem. Soc., Chem. Commun. 1979,449. (16) The results of experiments using commercial CuCl or recrystallized CuCl were essentially the same. (17)Marinovic, N. N.; Ramanathan, H. Tetrahedron Lett. 1983,24, 1871.
0022-326319511960-2322$09.00/0 0 1995 American Chemical Society
Communications
J. Org. Chem., Vol. 60, No. 8, 1995 2323
Scheme 1
Table 1. Copper(1)-MediatedConjugate Additionsa
3. LDA, THF, -78 OC u o 4. Me1 or NC-CRMe 3
LSnMe,
1 MeMgBr or EtMgBr Me CH2C12 Or E120 THF 4 R H (SPA.) 12. pTsOH, Et20-H20 r 5 R = Me (94%) I 6 R = C09'Me (77%) 1. DIBAH or MeMgBr Et20 1. DIBAH
2,F:
1
Et,O-H20
2. pTsOH, Et20 H20
entry
substrate
time (h)
product
yieldb (%)
1 2 3 4d 5' 6 7 8 9 10
7 8 9 9 9 10 11 12 23 24
0.5
13 14 15 15 15 16 17 18 25 26
96 82
1.0 1.0 1.0 3.0 0.5
1.0 0.5 3.0 1.5
48C
74 91 92 85 90 76 77
a Unless otherwise noted, all reactions were carried out with 2.5 equiv of CuCl in dry N,N-dimethylformamide at room temperature. Isolated yield of purified product. The major side products from this reaction were uncyclized substances in which the MejSn function of 9 had been replaced by H or C1. This reaction was carried out at 0 "C. e This reaction was performed employing 2.5 equiv of CuCN in dry dimethyl sulfoxide a t 60 "C.
interestingly and more importantly, use of coppeifl) cyanide in dry dimethyl sulfoxide a t 60 "C (entry 5) produced a highly satisfactory result.I8 8 R = Me (97%) 9 R = Et (92%) Table I
13R=H 14RrMe 15RsEt a
11 R IMe (89%)
Table I
16R=H 17R=Me
See Table I
18
LDA = i-F'rzNLi; DIBAH = i-Bu2AlH; p-TsOH = p-MeC6-
H4S03H.
Scheme 2
FSnMe, Me 21 R = H 22R=Me
Substituted bicyclo[3.3.0loct-6-en-3-onescan also be prepared by use of the new method. For example, treatment of the substrates 23 and 24 with CuCl in DMF at room temperature afforded the corresponding bicyclic products 25 and 26 in very good yields (Scheme 2, Table 1, entries 9 and 10). The relative configuration of each of the products 1318,25, and 26 was assigned on the basis of the assumption that the transition state producing the cis-fused product should, in each case, be less strained and, consequently, of lower energy than that leading to the corresponding trans-fused isomer. In this connection, it should be pointed out that substances 13 and 16 have been reported previously17 and that the lH NMR data reportedlg for the trans-fused epimer of 14 are distinctly different from those of the product derived from cyclization of 8. In conclusion, the studies summarized above have resulted in the development of a new five-membered ring annulation method in which the key step involves a previously unprecedented CuC1-mediated intramolecular conjugate addition of a vinyltrimethylstannyl function to an enone system.20 Obviously, many extensions to this work can be envisaged, and we are actively pursuing a number of possibilities.
Acknowledgment. We thank NSERC of Canada for financial assistance, a Postgraduate Scholarship (to E.J.M.) and a Postdoctoral Fellowship (to P.A.B.). 26 5 R ==M He
)-SnMe3 Me 23R=H 24R-Me
bicyclic product was accompanied by a number of monocyclic byproducts. Substrate 9 contains a ,8 ethyl group on the enone function, and apparently, the resultant (increased) steric encumberance at this center is deleterious to the facility of the intramolecular conjugate addition. Lowering of the reaction temperature to 0 "C resulted in a significant improvement (entry 41, but
Supplementary Material Available: Typical experimental procedures describing t h e preparation of (2)-3-(trimethylstannyl)-2-buten-l-ol a n d compounds 19,4,5, 11, a n d 17;'H NMR spectral d a t a for compounds 4-19a n d 21-26(6 pages). J0950062L
(18)The use of CuCN to promote intramolecularconjugate additions of vinyltrimethylstannyl functions to Michael acceptors is currently being investigated in more detail in our laboratories. (19)Narula, A. S.; Sethi, S. P. Tetrahedron Lett. 1984,25, 685. (20) A discussion of the mechanism of this process will be presented elsewhere.
