J. Org. Chem. 1994,59,6671-6682
6671
Xanthate Transfer Cyclization of Glycolic Acid-Derived Radicals. Synthesis of Five- to Eight-Membered Ring Ethers J a n H. Udding, J. P. M. Giesselink, Henk Hiemstra,* and W. Nico Speckamp* Department of Organic Chemistry, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands Received May 27, 1994@
A novel method for the preparation of functionalized five- to eight-membered ring ethers is described. This method involves the xanthate transfer radical cyclization of 2-(alken-l-oxy)-2-[(ethoxythiocarbonyl)sulfanyl]acetic acid methyl esters 6 to give good yields of xanthate-substituted five- to eight-membered ethers 7 and/or 8, depending on the length of the carbon chain. These cyclic ethers are usually obtained as mixtures of diastereomers. The cyclizations are performed a t 150-160 "C in tert-butylbenzene with di-tert-butyl peroxide as the initiator. This group-transfer radical cyclization was successfully applied in a total synthesis of lauthisan (44). The use of benzoyl xanthate (56) as a catalyst allows a visible light-induced xanthate transfer cyclization to a tetrahydrofuran in high yield.
Introduction The prevalence of the tetrahydropyran subunit in polyether natural products has stimulated the development of synthetic methods for this heterocycle. The preparation of oxygen heterocycles by cyclization reactions, involving free radical chain processes, is currently a topic of great R e ~ e n t l y ,we ~ reported a novel Cu(bpy)Cl-catalyzed process for the preparation of 2-carbomethoxy-3-(l-chloroalky1)tetrahydrofurans 2 via chlorine transfer radical cyclization reactions of methyl 2-(3-alken-1-oxy)9-chloroacetates (la,Scheme 1). This new method was developed as a modification of the reductive BusSnH-mediated radical cyclizations of the corresponding phenyl sulfides6z7 lb to tetrahydrofurans 3,since the atom transfer method Abstract published in Advance ACS Abstracts, October 1, 1994. (1)Beckwith, A. L. J.; Glover, S. A. Aust. J . Chem. 1987, 40, 157. (2) Surzur, J.-M.; Bertrand, M. P. Pure Appl. Chem. 1988,60,1659. (3) (a)Ueno, Y.; Chino, K.; Watanabe, M.; Moriya, 0.;Okawara, M. J . Am. Chem. SOC.1982,104,5564. (b) Stork, G.; Mook, R., Jr. J. Am. Chem. SOC.1983, 105, 3720. Stork, G . ; Mook, R., Jr.; Biller, S. A.; Rychnovsky, S. D. Ibid. 3741. Stork, G.; Sher, P. M. Ibid. 6766. Stork, G.; Sher, P. M. J . Am. Chem. SOC.1986, 108, 303. Stork, G.; Sher, P. M.; Chen, H.-L. Ibid. 6384. ( c ) Yadav, J. S.; Gadgil, V. R. J. Chem. SOC.,Chem. Commun. 1989, 1824. (d) Ichinose, Y.; Matsunaga, S.; Fugami, K.; Oshima, K.; Utimoto, K. TetrahedronLett. 1989,30,3155. (e) Nicolaou, K. C.; McGany, D. G.; Somers, P. K.; Veale, C. A.; Furst, G. T. J. Am. Chem. SOC.1987, 109, 2504; Nicolaou, K. C.; McGarry, D. G.; Somers, P. K.; Kim, B. H.; Ogilvie, W. W.; Yiannikouros, G.; Prasad, C. V. C.; Veale, C. A.; Hark, R. R. J. Am. Chem. SOC.1990, 112, 6263. (0 De Mesmaeker, A,; Hoffinann, P.; Ernst, B.; Hug, P.; Winkler, T. Tetrahedron Lett. 1989, 30, 6307, 6311. De Mesmaeker, A.; Waldner, A.; Hoffmann, P.; Mindt, T.; Hug, P.; Winkler, T. Synlett 1990, 687. (g) Rawal, V. H.; Singh, S. P.; Dufour, C.; Michoud, C. J. Org. Chem. 1991,56,5245. (h)Lubbers, T.; Schafer, H. J. Synlett 1990, 44. (4) (a) Belletire, J. L.; Mahmoodi, N. 0. Tetrahedron Lett. 1989,30, 4363. (b) Clough, J. M.; Pattenden, G.; Wight, P. G. Tetrahedron Lett. 1989, 30, 7469. ( c ) Nagashima, H.; Seki, K.; Ozaki, N.; Wakamatsu, H.; Itoh, K; Tomo, Y.; Tsuji, J . J . Org. Chem. 1990, 55, 985. (d) Hanessian, S.; Di Fabio, R.; Marcoux, J.-F.; Prud'homme, M. J . Org. Chem. 1990, 55, 3436. (e) Pirrung, F. 0. H.; Steeman, W. J. M.; Hiemstra, H.; Speckamp, W. N.; Kaptein, B.; Boesten, W. H. J.; Schoemaker, H. E.; Kamphuis, J. Tetrahedron Lett. 1992, 33, 5141. (5) (a) Udding, J. H.; Hiemstra, H.; Van Zanden, M. N. A,; Speckamp, W. N. Tetrahedron Lett. 1991, 32, 3123. (b) Udding, J . H.; Hiemstra, H.; Speckamp, W. N. J. Chem. Soc., Perkin Trans. 2 1992, 1529. ( c ) Udding, J . H.; Fraanje, J.; Goubitz, K.; Hiemstra, H.; Speckamp, W. N.; Kaptein, B.; Schoemaker, H. E.; Kamphuis, J. Tetrahedron: Asymmetry 1993, 4, 425. (d) Udding, J. H.; Tuijp, C. J . M.; Van Zanden, M. N. A.; Hiemstra, H.; Speckamp, W. N. J. Org. Chem. 1994,59, 1993. (6) Lolkema, L. D. M.; Hiemstra, H.; Al Ghouch, A. A.; Speckamp, W. N. Tetrahedron Lett. 1991, 32, 1491. @
results in a cyclization product containing a halogen functionality. While the copper catalyst is highly effective for radical cyclizations to tetrahydrofurans, it failed to promote 6-0 radical cyclization of higher homologues of la to provide functionalized t e t r a h y d r o p y r a n ~ . Similarly, ~ the BUSSnH-method failed to bring about 6-exo radical cyclization of the nonactivated alkene 4 (Scheme 21, and only quenching of the incipient radical by BusSnH, leading to 5, was observed.6 Apparently, 6-exo cyclization for 4 is too slow to be of use for this radical cyclization method, even under the high dilution (0.07 M) conditions employed for this reaction. In order to extend the scope of the cyclization reaction of a-alkoxy a-ester radicals, we searched for effective methods to promote 642x0 radical cyclization to tetrahydropyrans or to prepare even larger ring systems. Attention was focussed on atom- or group-transfer cyclization reactions other than the metal-promoted chlorine transfer ring closures studied thus far.8 A method which might be advantageous in this respect is the xanthate transfer radical cyclization technique. Zard and cow o r k e r ~ ~employed -'~ dithiocarbonates in group-transfer additions of alkyl and acyl radicals to olefins. Recently, we reported successful xanthate transfer radical additions of a glycine radical equivalent to alkenes, leading to various novel a-amino acid derivative^.'^ In this paper, we wish to report on the successful use of the xanthate transfer radical cyclization method in the synthesis of five- to eight-membered ring ethers. Thus, (7)Burke, S. D.; Rancourt, J. J . Am. Chem. SOC.1991,113, 2335. (8) For reviews of radical cyclizations including atom and group transfer methods, see: (a) Giese, B. Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds; Pergamon: Oxford, 1986. (b) Curran, D. P. Synthesis 1988,489. ( c ) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91, 1237. (d) Curran, D. P. In Comprehensiue Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 4, pp 715-832. (9)Delduc, P.; Tailhan, C.; Zard, S. Z. J . Chem. SOC., Chem. Commun. 1988,308. (10)Mestre, F.; Tailhan, C.; Zard, S. Z. Heterocycles 1989,28, 171. (11) Forbes, J. E.; Zard, S. Z. Tetrahedron Lett. 1989, 30, 4367. (12) Forbes, J. E.; Zard, S. Z. J . Am. Chem. SOC.1990, 112, 2034. (13) Forbes, J. E.; Tailhan, C.; Zard, S. Z. Tetrahedron Lett. 1990, 31, 2565. (14)Boivin, J.;Camara, J.; Zard, S. Z. J. Am. Chem. SOC.1992,114, 7909. ..
(15) Udding, J. H.; Hiemstra, H.; Speckamp, W. N. J . Org. Chem. 1994,59, 3721.
0022-326319411959-6671$04.50/0 0 1994 American Chemical Society
6672 J. Org. Chem., VoE. 59, No. 22, 1994
Udding et al. Scheme 1
3
1
Scheme 2 SPh
Bu3SnH
reflux
5 64%
Scheme 3
yJfR
-
Xanthate Transfer Cyclizations. The results of the radical cyclization reactions are summarized in Table 1. As the radical initiator, di-tert-butylperoxide (DTBP) was applied. When heated at temperatures above 130 "C, this peroxide generates two molecules of acetone and two methyl radicals, with a half-life time of 1 h.8a It was expected that these methyl radicals would initiate a radical chain reaction through addition to the thiocarbony1 g r o u ~ . ~All - ~reactions ~ were run at 150-160 "C and were monitored by thin layer chromatography. The solvent tert-butylbenzene was used, which is inert and permits high reaction temperatures at normal pressure (bp 169 "C). First, the radical cyclization of xanthate 9 was investigated (Table 1, entry 1). In the presence of 0.3 equiv of DTBP, a 0.5 M solution of xanthate 9 in tert-butylbenzene was heated a t 150-160 "C in an oil bath. TLC showed that virtually all of the starting material 9 was consumed in 20 min. Flash chromatography afforded the desired cyclization products 15 and 16 in 71% yield, with the 5-exo product 15 prevailing over the 6-endo product 16 (exolendo = 95:5). Both the Bu3SnH-mediated cyclization6 and the Cu(bpy)Cl-catalyzedcyclization5of the 2-oxa-5-hexenyl radical derived from 9 have been reported to give similar regio- and stereochemistries. Similar conditions were applied for the xanthate transfer cyclization of the 2-oxa-6-heptenyl radical precursors 10- 12,although slightly longer reaction times were necessary (0.5 h). Thus, xanthates 10-12 gave the cyclized products 17-20 in' 71-91% yield. In the case of the disubstituted alkenes 11 and 12,only the 6-exo cyclization products 19 and 20 were formed as inseparable mixtures. The cyclization of the monosubstituted alkene 10 shows that 'I-endo radical cyclization can compete with 6-exo radical cyclization, similar to the allcarbon system.sa Thus, a mixture of 6-exo cyclization product 17 and 7-endo cyclization product 18 was obtained. The stereochemistry of the cyclization products of 10 was further determined after treatment of the mixture of 17 and 18 with BuaSnH (Scheme 61, assuming that the reductive removal of the xanthate group is equally eficient for all isomers. In this way, an inseparable 50:50 mixture of 26 and the seven-membered ring ether 27 was obtained, with 26 present as a 25:75 mixture of cis and trans tetrahydropyrans. The Bu3SnHmediated analogous cyclization of the 2-oxa-6-heptenyl radical derived from 10 has been reported by Burke and Rancourt7 and gave comparable regio- and stereoselectivity, although in that case more of the seven-membered ring ether was produced. Similarly, Bu3SnH-mediated reduction of the crude mixture of four diastereomers of 19 (Scheme 7) gave a 35:65 mixture of tetrahydropyrans 28a and 28b in 81% yield, with the trans isomer predominating. The structural assignment of the cyclization products 15 and 17-20 was straightforward. The coupling constants for the OCH methine hydrogen atom in cis and trans tetrahydrofuran 15 (Table 1)compared well t o the
- CTonCozEt
r o * c o 2 E t benzene (0.07 M) 4
2
SCSOEt ( 2 S C S O E t
0+SCSoEr C02Me
0
6
7
CO,Me
and/or
(&R
0
C02Me
N
it will be shown that xanthates 6 (Scheme 3) are not only suitable for 5-exo radical cyclization (n = 11, but also for six-, seven-, and eight-membered ring formation (n = 2 and n = 31, leading to the xanthate transfer cyclization products 7 andor 8. Results and Discussion Synthesis of the Precursors. The precursors 9-14 (Table 1)for the radical cyclizations were prepared from the corresponding alcohols as outlined in Scheme 4. Treatment of the appropriate alcohol with methyl glyoxylate16 in CHZC12, followed by acetylation of the unstable hemiacetal with AczO in pyridine, gave a stable acetate, which was treated with AcCl and HCl(g)17to give the corresponding chloride in high yield as a sensitive oil. Substitution of the chlorine substituent with a xanthate group was achieved by treatment of the chloride with commercially available potassium 0-ethyl dithiocarbonate in CHzClz for 20 min. In this way the xanthates 9-14 were prepared in yields ranging between 74 and 91%. The synthesis of the chlorides used for the preparation of xanthates 9,11,and 13 has already been published.5d The alcohols used for the preparation of 10 and 14 were commercially available, while alcohol 25 used for the preparation of xanthate 13 was obtained from (2)-3hexenol as outlined in Scheme 5. Reaction of commercially available (Z1-3-hexenolwith methanesulfonyl chloride, followed by a reaction with NaCN impregnated on alumina,18 gave cyanide 24 in 97% yield. Hydrolysis of the cyanide with NaOH in methanol,19 followed by reduction with LiAlH4,20s21gave the desired alcohol 25 in 50% yield. (16) Generated from the commercially available methyl hemiacetal of methyl glyoxylate through distillation from phosphorus pentoxide (cf. Hook, J. M. Synth. Commun. 1984,14,83). (17) For a recent application of this procedure, see: Myrvold, S.; Reimer, L. M.; Pompliano, D. L.; Frost, J. W. J.Am. Chem SOC. 1989, 111, 1861. (18)Regen, S. L.; Quici, S.; Liaw, S.-J. J. Org. Chem. 1979,44,2029. (19)Aristoff, P. A.; Johnson, P. D.; Harrison, A. W. J. Am. Chem SOC.1985,107,7967. (20)Cimino, G.; Gavagnin, M.; Sodano, G.; Spinella, A.;Strazzullo, G. J . Org. Chem. 1987,52,2301. (21)Amundsen, L. H.; Nelson, L. S. J.Am Chem SOC.1961,73,242.
J . Org. Chem., Vol. 59, No. 22, 1994 6673
Xanthate Transfer Cyclization of Glycolic Acid-Derived Radicals
Table 1. Xanthate Transfer Radical Cyclizationof Precursors 9-14 ~
entry
substrate
time / initiator
yield
products (isomerratio)' SCSOEI
6 C 0 2 M e
1
0.3 h 0.3 equiv
9
95 : 5 cislfrans= 56:44
15a,b
71%
16a,b (5050) ,SCSOEI
y s c s o E t
0.5h 0.3 equiv
04C02Me
10
84% H
U
H
0.5h
0.3 equiv
91%
19a
19b
4 El
SCSOEI
0.5h 0.3 equiv
12
71 %
20a
20b
25:75
SCSOEI
2h
~s,so,t
ao%
0.2 equiv
21 (4 diastereomers)
SCSOEt SCSOEt
G W E t
6b
+ HhCO$de
'--
