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J. Am. Chem. Soc. 1996, 118, 4276-4283
Cyclization of N-Butyl-4-pentenylaminyl: Implications for the Cyclization of Alkenylaminyl Radicals Brendan J. Maxwell and John Tsanaktsidis*,† Contribution from the School of Chemistry, The UniVersity of Melbourne, ParkVille, Victoria 3052, Australia ReceiVed NoVember 6, 1995X
Abstract: The utility of arenesulfenamides as aminyl radical precursors has been clearly demonstrated. The cyclization of N-butyl-4-pentenylaminyl is shown to be a slow and irreversible process that is accelerated significantly by small amounts of bis(tributyltin) oxide.
Introduction
Scheme 1
The practice of chemical synthesis has benefited enormously, in recent times, from the maturation of the discipline of free radical chemistry.1 In particular, the development of several reliable, highly chemoselective, techniques for generating carbon-centered radicals, along with the deeper understanding of the factors that govern the regio- and diasteroselectivity of their inter- and intramolecular addition reactions to carboncarbon and carbon-heteroatom (N, O, S) multiple bonds, has been critical.2 The analogous reactions of heteroatom-centered radicals, however, have not found similar favor in modern chemical synthesis despite their potential for the construction of heterocyclic ring systems of various sizes. Indeed, recent contributions from the laboratories of Newcomb,3 Suginome,4 Kim,5 and Bowman6 on the cyclization reactions of alkenylaminyl radicals have served to focus considerable attention on the mechanistic features of these processes. † Current address: Division of Chemicals and Polymers, CSIRO, Private Bag 10, Rosebank MDC, Clayton, Victoria 3169, Australia. E-mail:
[email protected]. X Abstract published in AdVance ACS Abstracts, April 15, 1996. (1) (a) Motherwell, W. B.; Crich, D. Free-Radical Reactions in Organic Synthesis; Academic Press: London, 1992. (b) Curran, D. P. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 4, pp 715-831. (c) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. ReV. 1991, 91, 1237. (d) Thebtaranonth, C.; Thebtaranonth, Y. Tetrahedron, 1990, 46, 1385. (e) Ghosez, A.; Giese, B.; Mehl, W.; Metzger, J. O.; Zipse, H. In Methoden der Organischen Chemie, C-Radikale; Regitz, M., Giese, B., Eds. Georg Thieme: Stuttgart 1989; Vol. E 19a, Part 2. (2) (a) Rajanbabu, T. V. Acc. Chem. ReV. 1991, 24, 139. (b) Giese, B. Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds; Pergamon: Oxford, 1986. (c) Beckwith, A. L. J. Tetrahedron 1981, 3073 and references therein. (3) (a) Esker, J. L.; Newcomb, M. AdV. Heterocycl. Chem. 1993, 58, 1. (b) Newcomb, M.; Horner, J. H.; Shahin, H. Tetrahedron Lett. 1993, 34, 5523. (c) Newcomb, M.; Ha, C. Tetrahedron Lett. 1991, 32, 6493. (d) Newcomb, M.; Deeb, T. M.; Marquardt, D. J. Tetrahedron 1990, 46, 2317. (e) Newcomb, M.; Burchill, M. T.; Deeb, T. M. J. Am. Chem. Soc. 1988, 110, 6528. (f) Newcomb, M.; Deeb, T. M. J. Am. Chem. Soc. 1987, 109, 3163. (g) Newcomb, M.; Park, S.-U.; Kaplan, J.; Marquardt, D. J. Tetrahedron Lett. 1985, 26, 5651. (h) Newcomb, M.; Marquardt, D. J.; Deeb, T. M. Tetrahedron 1990, 46, 2329. (4) (a) Tokuda, M.; Fujita, H.; Suginome, H. J. Chem. Soc., Perkin Trans. 1 1994, 777. (b) Tokuda, M.; Miyamoto, T.; Fujita, H.; Suginome, H. Tetrahedron 1991, 47, 747. (c) Tokuda, M.; Yamada, Y.; Takagi, T.; Suginome, H. Tetrahedron 1987, 43, 281. (5) (a) Kim, S.; Yoon, K. S.; Kim, S. S.; Seo, H. S. Tetrahedron 1995, 51, 8437. (b) Kim, S.; Joe, G. H.; Do, J. Y. J. Am. Chem. Soc. 1994, 116, 5521. (c) Kim, S.; Joe, G. H.; Do, J. Y. J. Am. Chem. Soc. 1993, 115, 3328. (6) (a) Bowman, W. R.; Clark, D. N.; Marmon, R. J. Tetrahedron 1994, 50, 1275. (b) Bowman, W. R.; Clark, D. N.; Marmon, R. J. Tetrahedron 1994, 50, 1295. (c) Bowman, W. R.; Clark, D. N.; Marmon, R. J. Tetrahedron Lett. 1991, 32, 6441.
S0002-7863(95)03720-6 CCC: $12.00
Careful scrutiny of the available literature on the cyclization reactions of aminyl radicals reveals an uncertain situation. Pioneering studies by Michejda and co-workers7 on the cyclization reactions of N-propyl-4-pentenylaminyl (1), generated by photolysis of the corresponding symmetric tetrazene in cyclohexane at room temperature, indicate formation of N-propyl-2-methylpyrrolidine and N-propylpiperidine8 in 19% and 34% yields, respectively, whereas thermolysis (143 °C) of the tetrazene precursor in the same solvent produced the same products in 41% and 19% yields, respectively (Scheme 1). Subsequent efforts by Maeda and Ingold to measure the rate of cyclization of 1 and other representative alkenylaminyl radicals using kinetic EPR spectroscopy, however, were unsuccessful and led to the conclusion that cyclization of 1 at 25 °C is immeasurably slow (kc e 5 s-1).9,10 More recently, Newcomb and co-workers3d-f studied the cyclization of the alkenylaminyl 9, generated by photolysis of 2, in the presence of tributyltin hydride (Bu3SnH) and concluded that 9 undergoes reVersible cyclization (kc ) 3.5 × 103 s-1, k-c ) 1.0 × 104 s-1; K ) 0.35 at 50 °C)11 (Scheme 2), whereas Bowman and co-workers failed to observe cyclization of 9 in the presence of low concentrations of Bu3SnH in boiling cyclohexane.6 Against this uncertain background of conflicting reports we describe herein our results on this topic. Specifically, we demonstrate the utility of arenesulfenamides as aminyl radical precursors and we show that the cyclization of 9 is an irreversible process (i.e., kc . k-c) and that the rate of cyclization in benzene is enhanced (7) Michejda, C. J.; Campbell, D. H.; Sieh, D. H.; Koepke, S. R. In, Organic Free Radicals; Pryor, W. A., Ed.; ACS Symposium Series 69; American Chemical Society: Washington, DC, 1978; p 292. (8) This result is belived to be in error; see ref 3d. (9) Maeda, Y.; Ingold, K. U. J. Am. Chem. Soc. 1980, 102, 328. (10) This value is believed to be underestimated by about a factor of 5; see: Nazran, A. S.; Griller, D. J. Am. Chem. Soc. 1983, 105, 1970. (11) This value has been recently revised to 1; see ref 3b.
© 1996 American Chemical Society
Cyclization of N-Butyl-4-pentenylaminyl Scheme 2
significantly by the presence of small quantities of bis(tributyltin) oxide ((Bu3Sn)2O).12 Results and Discussion Studies in these12b and other6 laboratories have shown that benzenesulfenamides, PhSNR1R2, derived from dialkylamines undergo smooth homolytic substitution at sulfur by tributyltin radicals (Bu3Sn•), under standard reaction conditions (benzene, catatytic AIBN, 80 °C), thus producing the corresponding dialkylaminyl radical, R1R2N•. In our hands, however, purification of the benzenesulfenamide 3 by chromatography on either silica or neutral alumina was complicated by competitive hydrolysis.13 A search for more robust precursor substrates led to the investigation of several other arenesulfenamides, 4-8 (Scheme 2). The sulfenamides 3-8 were prepared from 11 upon treatment with the appropriate arenesulfenyl chloride (1318) in dry diethyl ether under nitrogen in the presence of triethylamine.14 The sulfenyl chlorides 13-18 were prepared from the corresponding disulfides 19-24, respectively, upon treatment with sulfuryl chloride in dichloromethane. 20, 21, and 23 were synthesized from p-aminobenzoic acid, 2-amino5-methoxybenzoic acid (25), and 2-amino-5-methylbenzoic acid,
(12) Part of this work has appeared in preliminary form: (a) Maxwell, B. J.; Tsanaktsidis, J. J. Chem. Soc., Chem. Commun. 1994, 533. (b) Beckwith, A. L. J.; Maxwell, B. J.; Tsanaktsidis, J. Aust. J. Chem. 1991, 44, 1809. (13) Cf. ref 6c. (14) (a) Craine, L.; Rabin, M. Chem. ReV. 1989, 89, 589. (b) Davis, F. A. Int. J. Sulfur Chem. 1973, 8, 71.
J. Am. Chem. Soc., Vol. 118, No. 18, 1996 4277 respectively, using standard literature methodology.15 Sulfenamides 4 and 5, like 3, were prone to hydrolysis upon exposure to silica, whereas 6, 7, and 8 could be chromatographed without incident on both silica gel and alumina. Exploratory experiments of 4, 6, 7, and 8 with 1 equiv of Bu3SnH in boiling benzene, in the presence of catalytic AIBN, resulted in the formation of 11 and 12, thus implicating the intermediacy of the aminyl 9 in these reactions, and at the same time demonstrated the superior reactivity of 8 (t1/2 ) ∼15 min at 80 °C) relative to 6 and 7 (t1/2 ) ∼5 h at 80 °C) toward Bu3Sn•. A disturbing feature of these experiments, however, was the lack of consistency in the observed ratio of 11 to 12 (i.e., ∼2 to >200), irrespective of the sulfenamide precursor used (Vide infra). In order to assess properly the effectiveness of arenesulfenamides as precursors for dialkylaminyl radicals, the radical chain reactions of the sulfenamide 8 and Bu3SnH16 in benzene (80 °C, catalytic AIBN) were performed under pseudo-firstorder conditions at several Bu3SnH concentrations. The resultant solutions were analyzed by gas chromatography and products identified by comparison with authentic materials. Response factors for 11 and 12, relative to an internal standard (nonane), were determined independently using authentic samples. The free radical nature of these reactions was demonstrated by a series of control experiments. For example, in the absence of Bu3SnH and AIBN, 8 was recovered unchanged; however, upon addition of Bu3SnH a slow reaction ensued, leading to a mixture of the amines 11 and 12. This process was interrupted completely upon addition of a radical inhibitor (2,4,6-tri-tertbutylphenol).17 Application of the steady state assumption to the kinetic analysis consistent with the mechanism depicted in Scheme 2 leads to the approximate rate equation (eq 1) where [Bu3SnH]m represents the mean Bu3SnH concentration during the reaction.3d,18 The results from these experiments are depicted graphically in
11/12 ) (kNHk-c)/(kCHkc) + (kNH/kc)[Bu3SnH]m
(1)
Figure 1. Consideration of the data revealed a variation in the ratio 11/12 which is inconsistent with eq 1. These observations prompted a thorough examination of our experimental technique, and ultimately led to the realization that small amounts of (Bu3Sn)2O,19,20 present in the Bu3SnH employed, may have been responsible for the observed variation in the ratio 11/12. The importance of (Bu3Sn)2O in these reactions was demonstrated beyond doubt through reaction of 8 with 1 equiv of Bu3SnH (0.05 M) in benzene (catalytic AIBN) in the presence of differing amounts of (Bu3Sn)2O. As illustrated by Figure 2, the presence of (Bu3Sn)2O, eVen at Very low concentrations, leads to significantly more cyclization. This previously unrecognized influence of (Bu3Sn)2O is suggestive of a Lewis acidtype interaction with the aminyl 921,22 and is reminiscent of the (15) Allen, C. F. H.; MacKay, D. D. Organic Syntheses; Wiley: New York, 1943; Collective Vol. 2, p 580. (16) Bu3SnH was prepared by NaBH4 reduction of (Bu3Sn)2O; see: Szammer, J.; O ¨ tvo¨s, L. Chem. Ind. 1988, 754. (17) A reviewer pointed out that 2,4,6-tri-tert-butylphenol does not trap carbon- or tin-centered radicals at significant rates and suggested that our observations may imply the generation of nitrogen-centered radicals in the control experiments. (18) Newcomb, M. Tetrahedron 1993, 49, 1151. (19) (Bu3Sn)2O is only one of several possible oxides of tin resulting from the aerobic oxidation of Bu3SnH20 potentially capable of influencing these reactions; every effort was made to minimize such impurities in these reactions. (20) Omae, I. Journal of Organometallic Chemistry Library; Organotin Chemistry. Elsevier: Amsterdam, 1989; Vol. 21, p 66. (21) 119Sn NMR experiments failed to identify a significant interaction between (Bu3Sn)2O and 8.
4278 J. Am. Chem. Soc., Vol. 118, No. 18, 1996
Figure 1. Results from the reactions of 8 with Bu3SnH (10 equiv) in benzene at 75 (*) and 80 (**) °C.
Maxwell and Tsanaktsidis
Figure 3. Results from the reactions of 2 with Bu3SnH (10 equiv) in benzene at 80 °C in the absence (data set 1) and the presence (data set 2) of (Bu3Sn)2O (1 equiv). Table 1. Reaction of 8 with Bu3SnH (1 equiv, 0.05 M) in Benzene (80 °C, AIBN) in the Presence of a Lewis Acid entry
additive
[additive] (mol %)
11/12
1 2 3 4 5 6 7
none (Bu3Sn)2O (Ph3Sn)2O Sn laddera Bu2Sn(Cl)OSn(Cl)tBu2 Bu3SnCl Bu2SnCl2
7 6 5 18 20 23
>200 2.6 4.7 17.4 21.4 >200 >200
a
Figure 2. Results from the reactions of 8 with Bu3SnH (10 equiv) in benzene at 75 °C in the presence of (Bu3Sn)2O.
acceleration afforded to alkenylaminyl radical cyclizations by protonation or complexation with a metal center.3c,23 The generality of this influence was investigated through the reactions of carbamate 2 with freshly distilled Bu3SnH (10 equiv) under pseudo-first-order conditions in boiling benzene both in the absence (data set 1) and in the presence (data set 2) of added (Bu3Sn)2O (1 equiv) (Figure 3). The significantly higher levels of cyclization of 9 in the latter case (data set 2) are suggestive of a specific interaction between 9 and (Bu3Sn)2O and not the precursor substrate. In order to shed more light on this influence, the reaction of 8 with 1 equiv of Bu3SnH (0.05 M) in benzene (catalytic AIBN) in the presence of several tin-containing Lewis acids was investigated (Table 1). Although consideration of these data provides little insight as to the nature of the putative interaction between 9 and the more active tin-based additives (entries 2-5), two points can be made. Firstly, there does not appear to be (22) For other Lewis acid influenced radical reactions, see: (a) Nishida, M.; Hayashi, H.; Yamaura, Y.; Nishida, A.; Kawahara, N. Tetrahedron Lett. 1995, 36, 269. (b) Renaud, P.; Moufid, N.; Kuo, L. H.; Curran, D. P. J. Org. Chem. 1994, 59, 3547. (c) Renaud, P.; Bourquard, T.; Gerster, M.; Moufid, N. Angew. Chem. Int. Ed. Engl. 1994, 33, 1601. (d) Yamamoto, Y.; Onuki, S.; Yumoto, M.; Asao, N. J. Am. Chem. Soc. 1994, 116, 421. (e) Nagano, H.; Kuno, Y. J. Chem. Soc., Chem. Commun. 1994, 987. (f) Feldman, K. S.; Romanelli, A. L.; Ruckle, R. E.; Miller, R. F. J. Am. Chem. Soc. 1988, 110, 3300. (g) Clark, T. J. Chem. Soc. Chem. Commun. 1986, 1774. (23) Stella, L. Angew. Chem., Int. Ed. Engl. 1983, 22, 337.
1-Hydroxy-3-(isothiocyanato)tetrabutyldistannoxane.
an obvious correlation between Lewis acid strength and activity, and secondly, the presence of the Sn-O-Sn linkage seems to be significant.24 Indeed, these observations led to the speculation that the interaction between (Bu3Sn)2O and 9 may be chelative in nature.25 These observations made it clear that a meaningful kinetic investigation of the cyclization of 9 using the Bu3SnH method was likely to be problematic. Accordingly, a full kinetic analysis of the cyclization of 9 in the presence of added (Bu3Sn)2O was undertaken. Treatment of 8 with excess Bu3SnH (benzene, catalytic AIBN) in the presence of 1 equiv of (Bu3Sn)2O, under pseudo-first-order conditions, produced the data represented graphically in Figure 4. The excellent fit of these data to eq 1 along with the effectively zero intercept vindicated this approach. This result is consistent with an irreversible cyclization of the (Bu3Sn)2O-complexed aminyl 9. In the light of these findings and the clear incompatability of the kinetic data depicted in Figure 1 with eq 1, the proposed equilibrium3d between 9 and 10 in the absence of (Bu3Sn)2O was questioned. Accordingly, the reaction of the selenide 26 and Bu3SnH was reinvestigated (Scheme 3). 26 was prepared according to the procedure of Newcomb and co-workers26 and treated with freshly distilled (0.01 and 0.005 M) Bu3SnH (10 equiv) in benzene (catalytic AIBN) at both 50 and 80 °C. GC analysis of the reaction mixtures failed to reveal the presence (99% conversion), after which they were opened, diluted with diethyl ether, and analyzed by gas chromatography. The results from four such reaction sets with sulfenamide 8 are displayed in Figure 1. For reactions conducted in the presence of (Bu3Sn)2O, 1 equiv of this material was added to the initial standard solution. Figure 4 shows the combined results for three data sets for reactions of sulfenamide 8, and Figure 6 contains the results from one reaction set for each of the sulfenamides 29-31. Reaction of Sulfenamide 8 with Bu3SnH in the Presence of Varying Amounts of (Bu3Sn)2O. Sulfenamide 8 (296 mg), AIBN (3 mg), and nonane (136 mg) were weighed into a 10 mL volumetric flask and sealed with a rubber septum. The flask was flushed with nitrogen and then freshly distilled Bu3SnH (282 mg, 1 equiv) added
J. Am. Chem. Soc., Vol. 118, No. 18, 1996 4283 by syringe. Addition of benzene diluted the sample up to 10 mL. A 1 mL portion of this solution was added to each of seven pyrex tubes under nitrogen and diluted with 0, 0.1, or 0.5 mL of a 0.0055 M solution of (Bu3Sn)2O in benzene or 0.01, 0.025, 0.05, or 0.1 mL neat (Bu3Sn)2O. Additional benzene was added to make up the samples to 2 mL. Degassing (freeze-pump-thaw) and sealing provide seven samples containing sulfenamide (0.05 M), Bu3SnH (0.05 M), and 0, 0.5, 2.8, 20, 51, 101, or 203 mol % (Bu3Sn)2O. These reaction vessels were then heated in a thermostated oil bath at 75 °C for 3 h, after which they were opened and analyzed by gas chromatography. The measured ratio 11/12 is shown graphically in Figure 2. Reaction of Selenide 26 with Bu3SnH. Selenide 26 (9.4 mg), AIBN (∼1 mg) and nonane were weighed into a 25 mL volumetric flask and sealed with a rubber septum. After purging with nitrogen, Bu3SnH (73 mg, 10 equiv) was added and benzene added to the mark. Two 2 mL samples (0.01 M Bu3SnH) were prepared in sealed tubes by the method described above and heated at either 50 or 80°C. Two samples containing 0.005 M Bu3SnH were also prepared as above by diluting 1 mL of the standard solution with 1 mL of benzene and heated at either 50 or 80 °C. After ∼3 h (at 80 °C) or ∼7 h (at 50 °C), analysis by GC indicated the presence of only cyclic amine 12 and no evidence of the acyclic amine 11. Reaction of Sulfenamide 8 with Bu3SnH in the Presence of Various Tin-Containing Lewis Acid Additives. A standard solution (A) containing sulfenamide 8 (0.3 g), Bu3SnH (0.27 mL; 1 equiv), nonane (151 mg), and benzene was prepared in a 10 mL volumetric flask. Three additional standard solutions were prepared containing Bu2SnCl2 (34 mg) (B), tBu2SnClOSnClnBu2 (48 mg) (C), or Bu3SnCl (32 mg) (D), in 5 mL of benzene. Three samples were then prepared in glass ampules under scrupulously oxygen free conditions containing 1 mL mL of A plus 1 mL of B, C, or D, and sealed under vacuum. Two control samples were prepared, both before and after preparing the other samples, containing A plus 1 mL of benzene. After heating for 2 h at 80 °C, the ampules were opened and analyzed by GC. The above procedure was repeated for addition of (Bu3Sn)2O (21 mg), (Ph3Sn)2O (21 mg) and 1-hydroxy-3-(isothiocyanato)tetrabutyldistannoxane34 (25 mg) in 5 mL of benzene. All four of the control reactions showed no cyclized amine 12. The measured ratio 11/12 is displayed in Table 1.
Acknowledgment. Financial support from the Univerisity of Melbourne (SIG) and the Australian Research Council is acknowledged. B.J.M. gratefully acknowledges the receipt of an Australian Post-Graduate Research Award. We thank Dr. Carl H. Schiesser for valuable discussions. JA953720S (34) Otera, J.; Dan-oh, N.; Nozaki, H. J. Org. Chem. 1991, 56, 5307.
