J. Org. Chem. 1992,57,1495-1503
1495
Stereochemistry of Metal-Halogen Exchange-Initiated Intramolecular Conjugate Addition Reactions in the Construction of 5-Membered Carbocycles Manning P. Cooke, Jr. Department of Chemistry, Washington State University, Pullman, Washington 99164 Received November 28, 1990
The stereochemistryof some lithium-iodine exchange-initiated cyclization reactions of model o-iodo, y-substituted activated olefins has been studied. The stereoselectivitiesof these anionic cyclization reactions have been found to be a function of the olefii activator employed, reaction conditions, Michael acceptor olefin geometry, the nature of the y-substituent, and, in some cases, the presence of additives. Cyclization reactions of iodides possessing E olefin geometry give a moderate preference for trans cyclopentane formation while 2 olefin geometry leads to extremely high (>300:1)trans product selectivity. Cyclization reactions of E olefins under radical conditions were found to be slightly more trans-selective than those observed under anionic conditions although 2 olefin geometry again promotes very high trans product selectivity. The presence of the allylic methoxyl group in (E)-7d leads to cis selectivity under both anionic and radical conditions. Intramolecular complexation involving the reactive carbon center and the methoxyl group is suggested in both modes as a possible explanation for this cis product selectivity.
Introduction Intramolecular reactions of reactive carbon centers with carbon-carbon multiple bonds are of considerable importance in the construction of cyclic systems.' Cyclization reactions of carbocations2and radicals3 have received greater attention than those involving electron-rich (carbanionic) centers. Studies of anionic cyclizations have centered largely on the intramolecular classical Michael reactions of enolates4and intramolecular carbometallation reactions of which the cyclization reactions of akenyL5and alkynyllithiuma derivatives are prominent. We have shown that metal-halogen exchange reactions may be used to introduce internal nucleophilic centers which may then undergo intramolecular conjugate addition reactions leading to 3-, 4-, 5-, and 6-membered rings as shown in Scheme L7 Initial efforts7*centered on the use ~
~
~~~~
(1) Thebtaranonth, C.; Thebtaranonth, Y. Tetrahedron 1990,43,1385. (2) (a) Johnson, W. S. Bioorg. Chem. 1976,5, 51. (b) Sutherland, J. K. Chem. SOC.Rev. 1980,265. (c) van Tamelen, E. E. Acc. Chem. Res. 1975,8,152. (d) Speckamp, N. Recl. J. R. Neth. Chem. SOC.1981,100, 345. (3) (a) Julia, M. Rec. Chem. Progr. 1964,25,3. (b) Nonhebel, D. C.;
Walton, J. Free Radical Chemistry; Cambridge University Press: Cambridge, 1974; Chapter 14. (c) Hart, D. J. Science 1984, 223, 883. (d) Giese, B. Radicals in Organic Synthesis; Pergamon: New York, 1986. (e) Neumann, W. P. Synthesis 1987, 665. (0Ramaiah, M. Tetrahedron 1987,43,3541. (9) Curran, D.P. Synthesis 1988,417,489. (4) (a) General review: Hudlicky, T.; Price, J. D. Chem. Rev. 1989,89, 1467. Recent samples intramolecular Michael reactions: (b) Stork, G.; Winkler, J. D.; Shiner, C. J.Am. Chem. SOC.1982,104,3767. (c) Stork, G.; Winkler, S. D.; Saccomano, N. A. Tetrahedron Lett. 1983,24,465. (d) Berthiaume, G.; Lsvallee, J.-F.; DesLongchamps,P. Ibid. 1986,27,5451. (e) Marion, J. P.; Long,J. K.J. Am. Chem. SOC.1988,110,7916. (fJSaito, S.; Hirohara, Y.; Narahara, 0.;Moriwake, T. Ibid. 1989, 111, 4533. (g) Uyehara, T.; Shida, N.; Yamamoto, Y. J. Chem. Soc., Chem. Commun. 1989, 113. (5) (a) Drozd, V. N.; Ustynyuk, Y. A.; Tseleva, M. A,; Dmitrievi, L. B. J.Cen. Chem. U.S.S.R. 1969,39, 1951. (b) Smith, M. J.; Wilson, S. E. Tetrahedron Lett. 1981,22,4615. (c)Bailey, W. F.; Patricia, J. J.; Nurmi, T. T.; Wang, W. Tetrahedron Lett. 1986,27,1861,1865. (d) Bailey, W. F.; Nurmi, T. T.; Patricia, J. J.; Wang, W. J. Am. Chem. SOC.1987,109, 2442. (e) Chamberlin, A. R.; Bloom, S. H.; Ceruini, L. A.; Fotsch, C. H. Ibid. 1988,110,4788. (0Broka, C. A.; Shen, T. Ibid. 1989,111,2981. (9) Paquette, L. A.; Gilday, J. P.; Maynard, G. D. J. Org. Chem. 1989,54, 5044. (h) Bailey, W. F.; Rossi, K.J. Am. Chem. SOC.1989,111,765. (i)
Row, G. A.: KOPPW, M. D.: Bartak, D. E.: Woolsev,N. F. J. Am. Chem. SOC.1985,107,-674% (6) (a) Bailey, W. F.; Ovaska, T. V.; Leipert, T. K. Tetrahedron Lett. 1989.30.3901. (b) Bailey, W. F.: Ovaska, T. V. Tetrahedron Lett. 1990.
31, 627. (7) (a) Cooke,M. P.! Jr.; Widener, R. K.J. Org. Chem. 1987,52,1381. (b) Cooke,M. P., Jr. Ibid. 1984,49,1144. (c) Organolithium intermediates
are depicted throughout aa monomersalthough they are likely aggregates: Wakerfield, B. J. The Chemistry of Organolithium Compounds; Pergamon: New York, 1974.
LEIJL LE Scheme I
Ii
1
2
3
Scheme I1
Q. 4a, X=I b, X=Li
5
6
of charge-protected olefin-activating groups such as acyl ylides (1, E = C(O)C(PPh,)COOR) whose carbonyl groups, by virtue of proximal negative charge, are highly resistant to nucleophilic attack by either the metdating agent (RLi) or the internally generated lithiated carbon center. It became apparent that lithium-iodine exchange reactions of primary iodides are in many cases so rapid8 that extraordinary protection of the Michael acceptor moiety often is not required and the use of simple unsaturated tert-butyl esters (1, E = COOBut) gives excellent results.% The intramolecular Michael addition approach offers a number of advantages over cyclization reactions of unactivated olefins. Lithium-iodine exchange-initiated cyclization reactions of substrates containing unactivated olefins are relatively slow, often requiring the presence of base-enhancing accelerating agents (e.g., TMEDA), leading to problems of adventitious quenching of highly basic intermediates and products5 and are, in general, restricted to monosubstituted olefins. On the other hand, cyclizations involving activated olefins (Michael acceptors) are usually rapid, even at low temperatures (-100 "C), tolerate olefin substitution, and lead to relatively stable anionic products such as enolates which are useful in subsequent reactions. We desired to extend the scope of these exchange-initiated conjugate addition reactions to systems involving sequential Michael reactions, thereby giving functionalized bicyclic ring systems as shown in Scheme 11. Of crucial (8) Cooke, M. P., Jr.; Houpis, I. N. Tetrahedron Lett. 1985,26,4987.
0022-3263/92/1957-1495$03.00/00 1992 American Chemical Society
1496 J. Org. Chem., Vol. 57,No. 5, 1992
Cooke Scheme V"
Scheme 111"
9
-a
11
10 0
0
-a
-1
12
-1
E-'la
-a 15
14
16
-1
E-'le
"(A) LDA, -78 O C then Et1 (94%); (B) DIBAL, -78 "C (88%); (C) (EtO)zP(0)C(PP~)COOEt,NaH, THF (94%); (D) NaI, acetone (93%).
"(A) CBr,, Ph3P, Zn (92%); (B) n-BuLi, THF, -78 OC then MeOH (100%); (C) NaI, acetone (80%); (D) Mes,BH, THF (100%).
Scheme IV"
Table I. Lithium-Iodine Exchange-Initiated Cyclization Reactions of Unsaturated Iodides 7 yield entry substrate RLi T ("C) additive t/c-8 (W)" 1 (E)-7a n-BuLi -78 3.3b 888 2 n-BuLi -100 3.3b w 3 t-BuLi -78 4.76 938 4 n-BuLi -78 LiIc 7.6 5 n-BuLi -78 LiId 6.3 6 n-BuLi -78 BF3-EhOe 4.4 7 (E)-7b n-BuLi -78 3.0 88 8 t-BuLi -78 3.9 88 9 n-BuLi -100 LiIc 3.2 82 10 n-BuLi -78 LiId 3.2 91 11 n-BuLi -78 BF3-EhOe 3.4 82 12 n-BuLi -78 TMEDA' 2.6 87 13 (E)-% t-BuLi -100 6.2h W 14 (Z)-7b n-BuLi -100 >300 15 (E)-7c n-BuLi -100 5.8 80s 16 (E)-7d n-BuLi -100 0.6 46 17 n-BuLi -100 LiI' 0.6 18 n-BuLi -100 TMEDAj 1.0 19 t-BuLi -100 1.0
-a
-1
13
E-'lb
" (A) (EtO)zP(0)CH2COOBut,NaH, THF (90%); (B) NaI, ace-
tone (94%).
-
importance to this scheme is the stereochemistry of the ring junction-forming first addition step (4b 5). The analogous cyclization of (4-methyl-5-hexeny1)lithium to [(2-methylcyclopentyl)methyl]lithiumoccurs with encouragingly high stereoselective (t/c = 13.5)5dwhich led us to undertake a model study of exchange-initiated intramolecular conjugate addition reactions leading to 1,2disubstituted cyclopentane derivatives (eq 1). We report
7a
b C
d e
E = C(O)C(PPh$OOEt, E = COOBu', R = Et E = COOBu', R = t-Bu E = COOBu', R = OMe E=BMcb,R=Et
R = Et
8
herein the results of this study which examined the stereochemistry of this cyclization reaction as a function of the nature of the olefin activating group, E, reaction conditions, the stereochemistry of the acceptor olefin, and the nature of allylic substituents. The cyclization reactions of the same substrates under radical conditions (Bu,SnH) also have been examined, and the results compared with those obtained under anionic cyclization conditions. Results and Discussion Acceptor Structure. The effect of acceptor structure on the stereochemical outcome of the reaction in eq 1was examined using three olefin activators previously found by us to be effective in exchange-initiated cyclization reactions: a change-protected acyl phosphoraneP9 (E)-7a, a tert-butoxycarbonyl (E)-7b,and a sterically encumbered boryl group,l0 (E)-7e. In each case a y-ethyl group (7, R = Et) was employed as a reasonable model for (9) (a) Cooke, M. P., Jr.; Goswami, R. J.Am. Chem. SOC.1977,99,642. (b) Cooke, M. P., Jr. Tetrahedron Lett. 1979,2199. (c) Cooke, M. P., Jr.; Burman, D. L. J. Org. Chem. 1982,47,4955. (d) Cooke, M. P., Jr. Ibid. 1982, 47, 4963. (e) Cooke, M. P., Jr.; Jaw, J.-Y. Ibid. 1986, 51, 758. (10) Cooke, M. P., Jr.; Widener, R. K. J. Am. Chem. SOC.1987, 109,
931.
a Yields determined by gas chromatography unless noted. bDetermined on the corresponding esters 8 (E = COOEt). BuLi-LiI (5.7 equiv) solution added to 7. dn-BuLi added to 7 containing 19 equiv of LiI. eBF3-Eh0(2.4 equiv) added to 7 prior to the addition of RLi. ITMEDA (4 equiv) present with 7. 8 Isolated yield. Determined on the corresponding alcohols, 8 (E = OH). n-BuLi solution containing 3 equiv of LiI was added to 7. jTMEDA (2.8 equiv) was present with 7.
the pendant side chain necessary to execute the sequential cyclization reactions in Scheme 11. The syntheses of these substrates are outlined in Schemes 111-V, respectively. Chloro aldehyde 11, the intermediate common to the synthesis of all three E substrates, was prepared (Scheme 111) by the low-temperature alkylation of the enolate of ester 9 with Et1 followed by partial reduction of the ester moiety in 10 with diisobutylaluminum hydride (DIBAL). It is noteworthy that the lithium enolate of 9 is well behaved at low temperatures (
