Cyclization of N-butyl-4-pentenylaminyl: Implications for the cyclization of alkenylaminyl radicals

Article abstract of DOI:10.1021/ja953720s

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.

Full text of DOI:10.1021/ja953720s

4276
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 carbon-
carbon 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 alkeny-
laminyl radicals have served to focus considerable attention on
the mechanistic features of these processes.
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 cy-
clization reactions of N-propyl-4-pentenylaminyl (1), generated
by photolysis of the corresponding symmetric tetrazene in
cyclohexane at room temperature, indicate formation of N-pro-
pyl-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
† Current address: Division of Chemicals and Polymers, CSIRO, Private
Bag 10, Rosebank MDC, Clayton, Victoria 3169, Australia. E-mail:
j.tsanaktsidis@chem.csiro.au.
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 Compre-
hensiVe 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.
(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.
S0002-7863(95)03720-6 CCC: $12.00 © 1996 American Chemical Society

Cyclization of N-Butyl-4-pentenylaminyl
J. Am. Chem. Soc., Vol. 118, No. 18, 1996 4277
Scheme 2
respectively, using standard literature methodology.15 Sulfe-
namides 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 experi-
ments 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 demon-
strated 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 arenesulfe-
namides 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-first-
order conditions at several Bu3SnH concentrations. The result-
ant 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
significantly by the presence of small quantities of bis(tributyltin)
oxide ((Bu3Sn)2O).12
Results and Discussion
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-tert-
butylphenol).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
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, purifica-
tion 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 (13-
18) 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-amino-
5-methoxybenzoic acid (25), and 2-amino-5-methylbenzoic acid,
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 (Bu3-
Sn)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 unrec-
ognized influence of (Bu3Sn)2O is suggestive of a Lewis acid-
type 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.
(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.

4278 J. Am. Chem. Soc., Vol. 118, No. 18, 1996
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).
Figure 1. Results from the reactions of 8 with Bu3SnH (10 equiv) in
benzene at 75 (*) and 80 (**) °C.
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
>200
1
2
3
4
5
6
7
none
(Bu3Sn)2O
7
6
5
18
20
23
2.6
(Ph3Sn)2O
4.7
17.4
21.4
Sn laddera
Bu2Sn(Cl)OSn(Cl)tBu2
Bu3SnCl
>200
>200
Bu2SnCl2
a 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 specula-
tion 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 ap-
proach. 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 (<0.5%)
of the acyclic amine 11. If this process were reversible, ∼5-
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 (Bu3-
Sn)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.
(24) The coproduct 2-benzothiazolyltributyltin sulfide, produced in situ
from the reaction of 8 with Bu3SnH, is unlikely to be important in these
reactions due to the absence of cyclization under “(Bu3Sn)2O-free”
conditions (see Table 1, entry 1).
(25) This assertion assumes that the key interaction between alkeny-
laminyls of the type 9 and (Bu3Sn)2O is with the nitrogen center. Although
this is reasonable, a discrete interaction between (Bu3Sn)2O and the olefinic
center bond cannot be excluded; see ref 22g.
(26) Newcomb, M.; Marquardt, D. J.; Kumar, M. U. Tetrahedron 1990,
46, 2345.
(23) Stella, L. Angew. Chem., Int. Ed. Engl. 1983, 22, 337.

Cyclization of N-Butyl-4-pentenylaminyl
J. Am. Chem. Soc., Vol. 118, No. 18, 1996 4279
Scheme 4
Figure 4. Results from the reactions of 8 with Bu3SnH (1 equiv) in
benzene at 80 °C in the presence of (Bu3Sn)2O (1 equiv).
findings, along with the experimental results of this study, are
consistent with a slow,9 irreVersible cyclization of 9 Via the
exo mode.
Figure 5. Ab initio calculated energy profile for the 5-exo-trig ring
closure of 27.
Scheme 3
The influence of substituents on the cyclization of 9 was then
investigated through the reactions of the sulfenamides 29, 30,
and 31 with Bu3SnH in the presence of added (Bu3Sn)2O. 29,
30, and 31 were prepared from the corresponding amines 32,
33, and 34 and 2-benzothiazolesulfenyl chloride (18) as
described above. The amines 32 and 34 were prepared from
35 and 36, respectively, which in turn were sysnthesized from
5-chloro-1-pentyne and 5-phenyl-4-pentenoic acid, respectively,
whereas 33 was available from (E)-4-hexen-1-ol by an adapta-
tion of a literature procedure.3e Authentic samples of the
pyrrolidines 43, 44, and 45 were prepared from the correspond-
ing phenyl selenides 40, 41, and 42,26 which were in turn
obtained from the carbamates 37, 38, and 393h (Scheme 4).
Treatment of 29, 30, and 31 with Bu3SnH in benzene at 80
°C in the presence of 1 equiv of (Bu3Sn)2O under pseudo-first-
order conditions as described above produced the results
displayed graphically in Figure 6. These data display a modest
acceleration in the rate of conversion of 29 and 30 to 43 and
44, respectively, relative to the parent cyclization (8 f 12),
whereas 31 was converted to 45 at a rate significantly greater
than that of the parent process (8 f 12). Although the
interpretation of these results is open to discussion, useful insight
is gained if they are related to the well-defined pattern of
6% of 11 would be expected under these reaction conditions.3d
It should be stressed at this point that the potential of (Bu3-
Sn)2O to alter the ring opening process (10 f 9) was fully
appreciated, and therefore, every effort was made to exclude
its presence.
As further Bu3SnH-mediated experimental investigations were
likely to be ambiguous in view of the difficulty of consistently
excluding the presence of (Bu3Sn)2O from such reactions, high-
level ab initio molecular orbital calculations on the cyclization
of N-methyl-N-4-pentenylaminyl (27) through both the exo and
endo modes of ring closure were performed.27 Three important
findings stemmed from this study: (i) the exo mode of
cyclization is preferred at the MP2/6-31G*//UHF/6-31G* level
of theory by 6.6 kcal/mol, (ii) there is a significant barrier to
cyclization Via the exo mode (14.1 kcal/mol), and (iii) conver-
sion of 27 to the corresponding pyrrolidinomethyl radical 28 is
significantly exothermic (14.8 kcal/mol) (Figure 5). These
(27) Maxwell, B. J.; Schiesser, C. H.; Smart, B. A.; Tsanaktsidis, J. J.
Chem. Soc., Perkin Trans. 2 1994, 2385.

4280 J. Am. Chem. Soc., Vol. 118, No. 18, 1996
Maxwell and Tsanaktsidis
with concentrated sulfuric acid for 15 h followed by desiccation
(MgSO4) and distillation from CaH2 under nitrogen.30 Bu3SnH was
prepared by reduction of (Bu3Sn)2O with sodium borohydride,16 distilled
at reduced pressure and stored under nitrogen at 4 °C. N-Butyl-4-
pentenylamine (11)3d, N-butyl-2-methylpyrrolidine (12),3d and N-butyl-
2-[(phenylseleno)methyl]pyrrolidine (26)26 were prepared using litera-
ture procedures, whereas p-aminobenzoic acid, 2-amino-5-methylbenzoic
acid, 5-methoxy-2-nitrobenzoic acid, and the disulfides 19, 22, and 24
were purchased from the Aldrich Chemical Co.
Dimethyl 4,4′-Dithiobisbenzoate (20). 4,4′-Dithiobisbenzoic acid,
prepared from para-aminobenzoic acid (31.5 g),15 was heated under
reflux in methanol (400 mL) containing concentrated sulfuric acid (10
mL) for 24 h. Removal of the methanol afforded a residue which was
dissolved in dichloromethane and washed with aqueous NaHCO3 and
water. Desiccation (MgSO4) followed by concentration (in Vacuo)
afforded a brown solid which after sublimation and recrystallization
(methanol) delivered the title disulfide 20 as a colorless solid (5.9 g,
43%), mp 127-8 °C (lit.31 mp 124 °C).
Figure 6. Results from the reactions of 8 (X ) H), 29 (X ) SiEt3),
30 (X ) CH3) and 31 (X ) Ph) with Bu3SnH (10 equiv) in benzene at
80 °C in the presence of (Bu3Sn)2O (1 equiv).
Dimethyl 2,2′-Dithiobis(5-methoxybenzoate) (21). 21 was pre-
pared from 2-amino-5-methoxybenzoic acid (25), in 44% crude yield
using literature methodology:15 1H NMR δ 3.81 (s, 3H), 3.98 (s, 3H),
6.99 (dd, J ) 8.9, 2.8 Hz, 1H), 7.56 (d, J ) 2.8 Hz, 1H), 7.65 (d, J )
8.9 Hz, 1H); 13C NMR δ 52.39, 55.56, 115.75, 119.86, 127.47, 128.05,
131.18, 157.63, 166.63; MS m/z 394 (M•+, 46), 362 (23), 197 (100),
167 (31); HRMS for C18H18O6S2, m/z calcd 394.0545, found 394.0551.
2-Amino-5-methoxybenzoic Acid (25). 5-Methoxy-2-nitrobenzoic
acid (2.0 g, 0.01 mol) was dissolved in absolute ethanol (50 mL) and
hydrogenated over Pd on C at atmospheric pressure. Filtration,
concentration (in Vacuo), and recrystallization (water) gave the title
acid 25 (1.26 g, 74%), mp 150-152 °C (lit.32 mp 149-151 °C).
Dimethyl 2,2′-Dithiobis(5-methylbenzoate) (23). Application of
literature methodology15 to 2-amino-5-methylbenzoic acid gave a 6:1
mixture of disulfide 23 and the corresponding trisulfide [dimethyl 2,2′-
trithiobis(5-methylbenzoate)], in 53% yield after esterification. Puri-
fication through a combination of radial chromatography and recrys-
tallization (methanol) delivered the disulfide 23 as a pale yellow solid
in 40% yield: mp 126-128 °C; 1H NMR δ 2.33 (s, 3H), 3.98 (s, 3H),
7.21 (dd, J ) 8.2, 1.8 Hz, 1H), 7.62 (d, J ) 8.2 Hz, 1H), 7.86 (d, J )
1.8 Hz, 1H); 13C NMR δ 20.46, 52.23, 125.81, 126.92, 131.82, 133.91,
135.28, 136.94, 166.90; MS m/z 362 (M•+, 22), 181 (100), 166 (20),
151 (18), 121 (21); HRMS for C18H18O4S2, m/z calcd 362.0646, found
362.0643. Dimethyl 2,2′-trithiobis(5-methylbenzoate) was isolated as
behavior encountered in the addition of carbon-centered
radicals to alkenes.28 For example, the modest acceleration
afforded by the electron-releasing triethylsilyl and methyl
substituents is notionally consistent with resonance stabilization
of a “product-like” (i.e., late) transition state, whereas the
electron-withdrawing phenyl substituent is found to have the
greatest influence presumably through a combination of coop-
erative electronic and resonance effects.28 Indeed, these results
are consistent with the view that alkenylaminyl radical cycliza-
tions in the presence of (Bu3Sn)2O are slow, irreversible
reactions which are accelerated by both electron-donating and
electron-withdrawing olefinic substituents through resonance
stabilization of the product-like transition state. This description
is in qualitative agreement with our theoretical calculations
which predict a considerable barrier to cyclization (14.1 kcal/
mol) and a significantly exothermic process (14.8 kcal/mol) for
the conversion of 27 to 28 in the absence of Lewis acid catalysis
and lead to the suggestion that the (Bu3Sn)2O-modified aminyls
are more akin to nucleophilic29 aminyl radicals, rather than
electrophilic23 aminium cation radicals, in their cyclization
reactions.
1
a colorless solid in 5% yield: mp 168-170 °C; H NMR δ 2.38 (s,
3H), 3.88 (s, 3H), 7.39 (d, J ) 8.2 Hz, 1H), 7.79 (s, 1H), 8.09 (d, J )
8.2 Hz, 1H); 13C NMR δ 20.63, 52.23, 127.50, 127.62, 131.64, 133.82,
136.09, 136.33, 166.78; MS m/z 394 (M•+, 6), 362 (8), 181 (100), 166
(16), 151 (15), 121 (18); HRMS for C18H18O4S3, m/z calcd 394.0367,
found 394.0382.
Experimental Section
General Procedures. Where necessary, reactions were conducted
in flame-dried glassware under an atmosphere of nitrogen, purified by
passage over activated 4Å molecular sieves and BASF R3-11 copper
catalyst. Melting points were determined using a Gallenkamp melting
point apparatus and are uncorrected. Boiling points are uncorrected
and correspond to the oven temperature of a GKR-51 Kugelrohr
apparatus. 1H and 13C NMR spectra were recorded as CDCl3 solutions
on a Varian Unity 300 spectrometer at 300 and 75 MHz, respectively.
Unless otherwise stated low- and high-resolution mass spectra were
recorded on a Joel JMS-AX505H spectrometer and a V.G. Micromass
7070F spectrometer, respectively, in electron impact mode at 70 eV.
Microanalyses were performed by either the Australian Microanalytical
Service, Melbourne, or Chemical and Micro Analytical Services Pty.
Ltd., Melbourne. Gas chromatography was conducted using either a
15 m DB-1301 or AT-1301 capillary column (i.d. 0.25 mm) on a
Hewlett-Packard 5890 gas chromatograph equipped with a flame
ionization detector. Peak areas were determined using a HP3394A
intergrator, and identification of products was made by comparison of
retention times with authentic samples. Product yields were determined
with correction for detector response by reference to an internal standard
(nonane). The lowest limit of detection of amine products was
conservatively estimated to be ∼0.5%. Benzene was purified by stirring
5-Chloro-1-(triethylsilyl)-1-pentene (35). 5-Chloropentyne (10.0
g, 0.1 mol), triethylsilane (11.3g, 0.1 mol), and chloroplatinic acid (∼10
mg) were stirred under nitrogen at ca. -5 to 0°C for 12 days. The
mixture was then filtered through silica gel, aided by a small portion
of diethyl ether, concentrated, and distilled (Kugelrohr, 92-94 °C, 2
mmHg) to give a clear liquid (17.7 g, 83%) which was shown to be a
85:15 mixture of 35 and the regioisomer 5-chloro-2-(triethylsilyl)-
1-pentene: 1H NMR (major isomer) δ 0.55 (q, J ) 7.9 Hz, 6H), 0.93
(t, J ) 7.9 Hz, 9H), 1.88 (qn, J ) 6.9 Hz, 2H), 2.20-2.32 (m, 2H),
3.53 (t, J ) 6.7 Hz, 2H), 5.62 (d, 18.8 Hz, 1H), 5.99 (dt, J ) 18.8, 6.4
Hz, 1H); 13C NMR (major isomer) δ 3.47, 7.33, 31.62, 33.95, 44.35,
127.64, 146.13; MS m/z 189 (M•+ - C2H5, 7), 123 (33), 121 (100), 95
(22), 93 (61), 58 (37). Anal. Calcd for C11H23ClSi: C, 60.37; H, 10.59.
Found: C, 60.39; H, 10.77.
(E)-N-Butyl-5-(triethylsilyl)-4-pentenamine (32). The silane 35
(3.9 g, 0.018 mol) (85:15 mixture of terminal and internal isomers) in
butylamine (20 mL) was heated under reflux for ∼18 h, under nitrogen,
then cooled to room temperature (RT), and concentrated under reduced
(30) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon Press: New York, 1992.
(31) Nair, M. G.; Campbell, P. T.; Baugh, C. M. J. Org. Chem. 1975,
40, 1745.
(28) Giese, B. Angew. Chem. Int Ed. Engl. 1983, 22, 753.
(29) Michejda, C. J.; Campbell, D. H. Tetrahedron Lett. 1977, 577.
(32) Bennett, O. F.; Johnson, J.; Tramondozzi, J. Org. Prep. Proc. Int.
1974, 6, 287.

Cyclization of N-Butyl-4-pentenylaminyl
J. Am. Chem. Soc., Vol. 118, No. 18, 1996 4281
pressure. The residue was taken up into diethyl ether (50 mL) and
washed with water (50 mL × 3) and brine (50 mL). Desiccation
(MgSO4) followed by removal of solvent (in Vacuo) furnished a yellow
oil which upon distillation (Kugelrohr, 120 °C, 0.3 mmHg) yielded 32
as a colorless oil (4.1 g, 90%) as a 85:15 mixture of regioisomers: 1H
NMR (major isomer) δ 0.54 (q, J ) 8.1 Hz, 6H), 0.86-1.00 (m, 12
H), 1.25-1.39 (m, 2H), 1.39-1.53 (m, 2H), 1.54-1.67 (m, 2H), 2.03-
2.21 (m, 2H), 2.52-2.66 (m, 4H), 5.56 (dt, J ) 18.2, 1.4 Hz, 1H),
6.03 (dt, J ) 18.2, 6.3 Hz, 1H); 13C NMR (major isomer) δ 3.49, 7.35,
14.01, 20.52, 29.19, 32.35, 34.78, 49.50, 49.76, 126.10, 147.95; MS
m/z 255 (M•+, 1), 115 (21), 87 (30), 86 (100), 70 (29), 58 (27); HRMS
for C15H33NSi, m/z calcd 255.2382, found 255.2384.
in dichloromethane (15 mL) (at reflux for 2,2′-dithiobis(benzothiazole))
containing a drop of pyridine was treated with sulfuryl chloride (6.4
mmol) and allowed to stir for ca. 10 min. The resultant sulfenyl
chloride solution was added dropwise by syringe to the corresponding
secondary amine (12.9 mmol) and triethylamine (∼5 equiv) in diethyl
ether (40 mL) maintained at 0 °C. The mixture was allowed to warm
to room temperature and left to stir for an additional 1-2 h, at which
time the mixture was diluted with diethyl ether (50 mL) and the layers
were separated. The aqueous layer was extracted with additional diethyl
ether, and the organics were combined and washed with brine (50 mL).
Desiccation (MgSO4) and concentration (in Vacuo) gave oils which
could be purified by either flash33 or radial chromatography or
distillation.
(E)-N-Butyl-4-hexenamine (33). p-Toluenesulfonyl chloride (36.0
g, 0.19mol) was added to a solution of (E)-4-hexenol (16.0 g, 0.16
mol) in pyridine (120 mL) at 0 °C, and then allowed to stir at room
temperature for 1.5 h. The mixture was poured onto crushed ice (300
g) and extracted with diethyl ether (3 × 200 mL). The ether portions
were combined and washed with 10% HCl solution (2 × 100 mL) and
brine (1 × 100 mL). Desiccation (MgSO4), followed by concentration
(in Vacuo), gave the corresponding tosylate, which was treated with
butylamine (200 mL) and heated to reflux for ca. 2 days. The excess
butylamine was removed by rotary evaporation and the residue diluted
with 10% NaOH (400 mL) and extracted with diethyl ether (3 × 200
mL). The combined ethereal portions were then washed with brine (2
× 200 mL), dried (MgSO4), and concentrated (in Vacuo) to yield a
yellow oil. Distillation (Kugelrohr, 81-84°C, 10 mmHg) afforded 33
as a colorless liquid (19.0 g, 77%): 1H NMR δ 0.70-1.0 (br s, 1H),
0.92 (t, J ) 7.4 Hz, 3H), 1.26-1.61 (m, 6H), 1.64 (d, J ) 4.0 Hz,
3H), 1.96-2.06 (m, 2H), 2.59 (t, J ) 7.4 Hz, 4H) 5.30-5.55 (m, 2H);
13C NMR δ 14.03, 17.89, 20.53, 30.01, 30.44, 32.39, 49.65, 49.79,
124.97, 131.01; MS m/z 155 (M•+, 2%), 112 (43), 86 (100), 70 (28),
56 (22), 54 (50); HRMS for C10H21N, m/z calcd 155.1674, found
155.1675.
N-Butyl-N-4-pentenyl-4-carbomethoxybenzenesulfenamide (4)
was obtained as a pale yellow oil in 57% yield after flash chromatog-
raphy on neutral alumina (1.5% EtOAc/hexanes): 1H NMR (400 MHz)
δ 0.90 (t, J ) 7.3 Hz, 3H), 1.20-1.40 (m, 2H), 1.52-1.64 (m, 2H),
1.64-1.76 (m, 2H), 2.00-2.10 (m, 2H), 3.00-3.04 (m, 4H), 3.89 (s,
3H), 4.90-5.05 (m, 2H), 5.72-5.84 (m, 1H), 7.28 (d, J ) 8.8 Hz,
2H), 7.93 (d, J ) 8.8 Hz, 2H); 13C NMR (100 MHz) δ 13.95, 20.15,
27.67, 30.65, 31.10, 51.91, 57.97, 58.52, 114.84, 121.88, 126.23, 129.75,
138.14, 150.18, 166.95; MS m/z 307 (M•+, 17), 264 (50), 252 (66),
210 (100), 167 (26), 139 (22), 137 (22), 126 (37), 86 (45), 69 (22), 57
(26), 44 (20), 42 (26), 41 (55), 29 (25); HRMS for C17H25NO2S, m/z
calcd 307.1606, found 307.1606.
N-Butyl-N-4-pentenyl-2-carbomethoxy-4-methoxybenzenesulfe-
namide (5) was obtained as a pale yellow oil in 57% yield after
distillation (Kugelrohr, 172°C, 0.02 mmHg): 1H NMR δ 0.88 (t, J )
7.3 Hz, 3H), 1.20-1.40 (m, 2H), 1.50-1.80 (m, 4H), 1.95-2.15 (m,
2H), 2.90-3.10 (m, 4H), 3.83 (s, 3H), 3.91 (s, 3H), 4.85-5.10 (m,
2H), 5.65-5.90 (m, 1H), 7.11 (dd, J ) 8.8, 2.7 Hz, 1H), 7.53 (d, J )
2.7 Hz, 1H), 7.71 (d, J ) 8.8 Hz, 1H); 13C NMR δ 13.96, 20.33, 27.81,
30.76, 31.35, 52.04, 55.61, 57.74, 58.23, 114.63, 115.09, 120.06, 123.85,
124.74, 138.37, 141.03, 156.30, 166.64; MS m/z 337 (M•+, 9), 197
(100), 167 (28), 126 (39), 98 (22), 86 (43); HRMS for C18H27NO3S,
m/z calcd 337.1712, found 337.1719.
N-Butyl-(E)-5-Phenyl-4-pentenamide (36). Oxalyl chloride (3.6
g, 0.029 mol) was added to a dichloromethane (25 mL) solution of
(E)-5-phenyl-4-pentenoic acid4b (4.6 g, 0.026 mol) containing a few
drops of DMF. This was allowed to stir at room temperature for ∼30
min before being added dropwise to a stirred mixture of butylamine
(1.9 g, 0.032 mol) in aqueous sodium hydroxide (0.9 M, 30 mL). After
stirring for ∼15 min, the layers were separated, and the aqueous layer
was extracted with a portion of dichloromethane (30 mL). The organics
were combined, washed with water (50 mL) and brine (50 mL), dried
(MgSO4), and concentrated (in Vacuo) to give a yellow solid which,
after purification by radial chromatography (40% EtOAc in hexanes)
and recrystallization from hexanes/diethyl ether, yielded the required
N-Butyl-4-pentenyl-2-carbomethoxybenzenesulfenamide (6) was
obtained as a pale yellow oil in 52% yield after radial chromatography
on silica (10% EtOAc/hexanes): 1H NMR δ 0.88 (t, J ) 7.3 Hz, 3H),
1.20-1.40 (m, 2H), 1.50-1.80 (m, 4H), 2.00-2.10 (m, 2H), 2.95-
3.10 (m, 4H), 3.90 (s, 3H), 4.90-5.03 (m, 2H), 5.65-5.90 (m, 1H),
7.11 (t, J ) 7.4 Hz, 1H), 7.44-7.52 (m, 1H), 7.83 (d, J ) 8.3 Hz,
1H), 8.00 (dd, J ) 7.9, 1.4 Hz, 1H); 13C NMR (benzene-d6) δ 14.10,
20.61, 28.12, 31.04, 31.63, 51.49, 57.84, 58.31, 114.85, 123.44, 123.67,
124.20, 131.63, 132.27, 138.48, 150.72, 166.42; MS m/z 307 (M•+
,
1
11), 167 (100), 152 (12), 86 (11); HRMS for C17H25NO2S, m/z calcd
307.1606, found 307.1603.
amide 36 as white needles (5.1 g, 61%): mp 77-78 °C; H NMR δ
0.89 (t, J ) 7.3 Hz, 3H), 1.24-139 (m, 2H), 1.40-1.52 (m, 2H), 2.32
(t, J ) 7.4 Hz, 2H), 2.55 (q, J ) 7.2 Hz, 2H), 3.25 (q, J ) 6.7 Hz,
2H), 5.55 (br s, 1H), 6.20 (dt, J ) 15.7, 6.9 Hz, 1H), 6.43 (d, J ) 15.7
Hz, 1H), 7.16-7.36 (m, 5H); 13C NMR δ 13.68, 20.03, 29.03, 31.71,
36.43, 39.22, 125.98, 127.09, 128.45, 128.78, 130.95, 137.31, 171.97;
MS m/z 231 (M•+, 100), 140 (27), 131 (23), 130 (36), 129 (21), 117
(90), 115 (37), 104 (21), 91 (52), 56 (80). Anal. Calcd for C15H21-
NO: C, 77.88; H, 9.15; N, 6.05. Found: C, 77.86; H, 8.92; N, 5.92.
N-Butyl-5-phenyl-4-pentenamine (34). A solution of LiAlH4 in
THF (1.0M, 3.5 mL) was added slowly to a solution of 36 (0.82 g, 3.6
mmol) in THF (5 mL) under an atmosphere of nitrogen and then heated
under reflux for 2 h. The cooled reaction mixture was treated with a
minimum amount of saturated aqueous Na2SO4 and then filtered through
a pad of Celite and the filtrate concentrated under reduced pressure.
Distillation (Kugelrohr, 121°C, 0.1 mmHg) of the resulting residue
afforded 34 as a colorless liquid (0.52 g, 68%) which was shown to be
a ∼3:1 mixture of E/Z isomers: 1H NMR δ 0.91 (t, J ) 7.3 Hz, 3H),
1.20-1.58 (m, 5H), 1.58-1.72 (m, 2H), 2.26 (q, J ) 7.2 Hz, 2H),
2.56-2.70 (m, 4H), 6.18-6.28 (m, 1H), 6.40 (d, J ) 16.0 Hz, 1H),
7.14-7.37 (m, 5H); 13C NMR (major isomer) δ 13.93, 20.42, 29.63,
30.78, 32.17, 49.44, 49.63, 125.81, 126.74, 128.35, 129.97, 130.31,
137.62; MS m/z 217 (M•+, 43), 174 (25), 129 (28), 117 (40), 115 (40),
112 (52), 91 (67), 86 (100), 70 (23), 56 (30), 55 (22); HRMS for
C15H23N, m/z calcd 217.1830, found 217.1822.
N-Butyl-N-4-pentenyl-2-carbomethoxy-4-methylbenzenesulfena-
mide (7) was obtained as a pale yellow oil in 74% yield after radial
chromatography on silica (10-30% EtOAc/hexanes): 1H NMR δ 0.89
(t, J ) 7.1 Hz, 3H), 1.20-1.40 (m, 2H), 1.50-1.80 (m, 4H), 1.95-
2.15 (m, 2H), 2.35 (s, 3H), 2.95-3.10 (m, 4H), 3.90 (s, 3H), 4.85-
5.10 (m, 2H), 5.65-5.90 (m, 1H), 7.31 (d, J ) 8.6 Hz, 1H), 7.70 (d,
J ) 8.6 Hz, 1H), 7.82 (s, 1H); 13C NMR δ 13.95, 20.30, 20.43, 27.77,
30.72, 31.32, 51.89, 57.63, 58.13, 114.60, 123.02, 123.36, 131.58,
132.89, 133.39, 138.34, 146.61, 166.92; MS m/z 321 (M•+, 9), 181
(100), 166 (15), 151 (15), 121 (13); HRMS for C18H27NO2S, m/z calcd
321.1762, found 321.1754.
N-Butyl-N-4-pentenyl-2-benzothiazolesulfenamide (8) was ob-
tained as a pale yellow oil in 62% yield after flash chromatography on
silica (10-30% EtOAc/hexanes): 1H NMR δ 0.93 (t, J ) 7.4 Hz, 3H),
1.24-1.44 (m, 2H), 1.60-1.73 (m, 2H), 1.73-1.85 (m, 2H), 2.04-
2.16 (m, 2H), 3.06-3.16 (m, 4H), 4.93-5.08 (m, 2H), 5.72-5.88 (m,
1H), 7.25 (t, J ) 7.6 Hz, 1H), 7.38 (t, J ) 7.6 Hz, 1H), 7.78 (d, J )
8.0 Hz, 1H), 7.81 (d, J ) 8.0 Hz, 1H); 13C NMR δ 13.90, 20.13, 27.54,
30.50, 31.04, 57.98, 58.52, 115.01, 120.89, 121.55, 123.52, 125.75,
135.00, 137.90, 154.93, 177.89; MS m/z 306 (M•+, 0.2), 167 (44), 140
(62), 85 (65), 83 (100); HRMS for C16H22N2S2, m/z calcd 306.1224,
found 306.1230.
N-Butyl-N-[5-(triethylsilyl)-4-pentenyl]-2-benzothiazolesulfena-
mide (29) was obtained as a pale yellow oil in 66% yield after radial
General Procedure for the Preparation of Arenesulfenamides
3-8 and 29-31. A solution of the appropriate disulfide (6.3 mmol)
(33) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.

4282 J. Am. Chem. Soc., Vol. 118, No. 18, 1996
Maxwell and Tsanaktsidis
chromatography on silica (10-30% EtOAc/hexanes): 1H NMR (major
isomer) δ 0.53 (q, J ) 7.9 Hz, 6H), 0.91 (t, J ) 7.9 Hz, 9H), 0.92 (t,
J ) 7.3 Hz, 3H), 1.26-1.44 (m, 2H), 1.58-1.73 (m, 2H), 1.73-1.90
(m, 2H), 2.08-2.26 (m, 2H), 3.00-3.22 (m, 4H), 5.58 (d, J ) 18.5
Hz, 1H), 6.01 (dt, J ) 18.5, 6.2 Hz, 1H), 7.24 (t, 7.6 Hz, 1H), 7.38 (t,
J ) 7.6 Hz, 1H), 7.77 (d, J ) 7.6 Hz, 1H), 7.82 (d, J ) 7.6 Hz, 1H);
13C NMR (major isomer) δ 3.51, 7.33, 13.91, 20.15, 27.38, 30.53, 34.18,
57.83, 58.55, 120.89, 121.56, 123.51, 125.75, 126.79, 135.04, 147.29,
154.95, 177.92; MS m/z 420 (M•+, 1), 255 (24), 254 (100), 167 (53),
126 (28), 115 (48), 87 (48), 86 (26), 58 (30). Anal. Calcd for
C22H36N2S2Si: C, 62.8; H, 8.6. Found: C, 62.7; H, 8.8.
N-Butyl-N-4-hexenyl-2-benzothiazolesulfenamide (30) was ob-
tained as a pale yellow oil in 57% yield after radial chromatography
on silica (35% CH2Cl2/hexanes): 1H NMR δ 0.92 (t, J ) 7.1 Hz, 3H),
1.28-1.44 (m, 2H), 1.56-1.80 (m, 7H), 1.96-2.12 (m, 2H), 3.04-
3.15 (m, 4H), 5.28-5.52 (m, 2H), 7.25 (t, J ) 7.8 Hz, 1H), 7.38 (t, J
) 7.8 Hz, 1H), 7.74-7.84 (m, 2H); 13C NMR δ 13.93, 17.86, 20.16,
28.20, 29.91, 30.50, 58.12, 58.51, 120.90, 121.53, 123.48, 125.52,
125.75, 130.42, 135.01, 154.98, 178.32; MS m/z 320 (M•+, 1), 167
(52), 166 (23), 154 (100), 54 (23); HRMS for C17H24N2S2, m/z calcd
320.1381, found 320.1387.
N-Butyl-N-(5-phenyl-4-pentenyl)-2-benzothiazolesulfenamide (31)
was obtained as a pale yellow oil in 44% yield after radial chroma-
tography on silica (35% CH2Cl2/hexanes): 1H NMR δ 0.92 (t, J ) 7.3
Hz, 3H), 1.25-1.45 (m, 2H), 1.56-1.76 (m, 2H), 1.80-1.94 (m, 2H),
2.27 (q, J ) 7.2 Hz, 2H), 3.04-3.22 (m, 4H), 6.20 (dt, J ) 15.8, 6.8
Hz, 1H), 6.40 (d, J ) 15.8 Hz, 1H), 7.10-7.44 (m, 7H), 7.78 (d, J )
7.9 Hz, 1H), 7.82 (d, J ) 7.9 Hz, 1H); 13C NMR (major isomer) δ
13.96, 20.15, 28.00, 30.38, 30.49, 57.99, 58.64, 120.91, 121.53, 123.53,
125.78, 125.91, 126.92, 128.45, 129.77, 130.46, 134.95, 137.51, 154.90,
177.99; MS m/z 382 (M•+, 0.3), 218 (34), 216 (56), 167 (70), 166 (34),
126 (76), 124 (23), 117 (44), 91 (49), 86 (100), 56 (27); HRMS for
C22H26N2S2, m/z calcd 382.1537, found 382.1529.
(q, J ) 6.6 Hz, 2H), 2.62 (q, J ) 6.6 Hz, 0.25H), 3.25-3.64 (m, 4H),
6.14-6.29 (m, 1H), 6.36-6.49 (m, 1H), 6.54-6.64 (m, 1H), 7.12-
7.40 (m, 6H), 7.56-7.72 (m, 2H); 13C NMR δ 13.68, 13.75, 19.80,
19.95, 27.01, 28.14, 29.48, 30.06, 30.18, 30.64, 47.29, 47.62, 48.58,
48.86, 112.12, 125.86, 126.83, 126.94, 128.28, 128.35, 128.40, 129.20,
129.40, 130.48, 130.61, 133.37, 136.97, 138.62, 151.51, 151.57, 176.21;
MS m/z 370 (M•+, 11), 246 (20), 244 (92), 243 (27), 126 (36), 117
(33), 111 (24), 91 (100), 86 (30), 78 (22), 56 (29); HRMS for
C21H26N2O2S, m/z calcd 370.1715, found 370.1702.
General Procedure30 for the Preparation of the Phenylseleno
Pyrrolidines 40-42. N-Hydroxypyridine-2-thione carbamate (1.0
mmol), malonic acid (3.0 mmol), diphenyl diselenide (2.0 mmol), and
acetonitrile (10 mL) were placed in a two necked round bottom flask
under a nitrogen atmosphere. The flask was then irradiated with a 100
W tungsten lamp for 3 h at 20-30 °C. The solvent was removed under
reduced pressure and the residue taken up into ether and extracted twice
with 10% HCl solution. The combined aqueous portions were basified
with 10% NaOH solution, extracted (twice) into ether, and concentrated
under vacuum. The residue was dissolved in ∼5 mL of ethanol and
NaBH4 added until the solution became nearly colorless. Ether and
10% NaOH were added, and the organic layer was dried (MgSO4) and
concentrated to yield the crude phenylseleno pyrrolidines which were
further purified by radial chromatography on silica (EtOAc/hexanes).
N-Butyl-2-[(1-phenylseleno)(triethylsilyl)methyl]pyrrolidine (40)
was obtained as a yellow oil in 57% yield: 1H NMR δ 0.50-1.20 (m,
19H), 1.20-2.30 (m, 9H), 2.30-3.20 (m, 4H), 7.10-7.35 (m, 3H),
7.45-7.54 (m, 1H), 7.62-7.72 (m, 1H); 13C NMR δ 3.36, 3.79, 4.75,
7.77, 7.91, 8.25, 14.14, 20.79, 20.85, 20.94, 22.41, 22.82, 30.32, 30.79,
32.76, 35.02, 53.16, 54.20, 54.27, 54.71, 58.82, 65.75, 68.36, 126.36,
126.42, 128.22, 128.31, 128.79, 132.12, 133.91, 138.52; MS m/z 411
(M•+ 1), 126 (72), 70 (44), 58 (100); HRMS for C21H37NSeSi, m/z
calcd 411.1860, found 411.1847.
N-Butyl-2-[1-(phenylseleno)ethyl]pyrrolidine (41) was obtained as
a yellow oil in 50% yield: 1H NMR δ 0.80-1.00 (m, 3H), 1.20-1.56
(m, 7H), 1.60-1.94 (m, 4H), 2.05-2.22 (m, 2H), 2.38-2.50 (m, 0.5H),
2.58-2.76 (m, 1H), 2.76-2.88 (m, 0.5H), 3.10-3.26 (m, 1H), 3.42-
3.56 (m, 0.5H), 3.60-3.73 (m, 0.5H), 7.18-7.32 (m, 3H), 7.51-7.64
(m, 2H); 13C NMR δ 14.06, 14.14, 15.56, 19.65, 20.65, 20.80, 22.59,
23.36, 26.50, 27.45, 30.76, 31.00, 42.49, 43.54, 54.15, 54.55, 54.74,
67.56, 69.12, 127.02, 128.59, 128.86, 134.07, 135.50, 160.47; MS (CI)
m/z 314 (4), 312 (22), 310 (19), 308 (8), 154 (57), 126 (100); HRMS
(CI) for C16H26SeN m/z calcd (M + H), 312.1230, found 312.1243.
N-Butyl-2-[phenyl(phenylseleno)methyl]pyrrolidine (42) was ob-
tained as a yellow oil in 51% yield: 1H NMR δ 0.84 (t, J ) 7.2 Hz,
1.8H), 0.92 (t, J ) 7.2 Hz, 1.2 H), 1.10-1.92 (m, 7H), 1.94-2.38 (m,
3H), 2.54-2.90 (m, 2H), 3.04-3.32 (m, 1H), 4.41 (d, J ) 6.5 Hz, 0.4
H), 4.51 (d, J ) 5.2 Hz, 0.6H), 7.00-7.36 (m, 10H); 13C NMR δ 14.05,
14.14, 20.57, 22.84, 23.76, 29.47, 29.50, 30.70, 31.22, 53.97, 54.36,
55.00, 55.04, 55.88, 56.83, 69.10, 69.24, 126.42, 126.48, 126.73, 126.77,
127.64, 127.80, 128.36, 128.38, 129.17, 129.27, 130.38, 130.60, 134.20,
134.26, 140.79, 141.40; MS m/z 216 (M•+ - SeC6H5, 4), 126 (100),
70 (13); HRMS for C15H22N, m/z calcd 216.1752, found 216.1742.
General Procedure for the Preparation of the Pyrrolidines 43-
45. Seleno pyrrolidine 40, 41, or 42 and AIBN (catalytic amount) were
dissolved in benzene and heated to reflux under a nitrogen atmosphere
for ∼5 min, and then Bu3SnH (1.1 equiv, 0.06-0.15 M) was added by
syringe. After ∼2 h at reflux the mixture was allowed to cool and
extracted with 10% HCl solution (10% H2SO4 used for 43). The
aqueous layer was then basified with 10% NaOH and extracted into
diethyl ether. Desiccation (MgSO4) and removal of solvent (in Vacuo)
gave a crude product which was distilled (Kugelrohr) to yield the
pyrrolidines as colorless oils.
General Procedure3h for the preparation of N-Hydroxypyridine-
2-thione Carbamates 37-39. Phosgene (3.4 mL, 20% solution in
toluene) was added to a suspension of the sodium salt of N-hydroxy-
pyridine-2-thione (6.4 mmol) in benzene at 0 °C. The resultant solution
was maintained at 0 °C for a further 45 min and then allowed to warm
to room temperature and stirred for ∼1 h. The flask was then shielded
from light and a solution of triethylamine (6.4 mmol) and the
appropriate secondary amine (6.4 mmol) in benzene (5 mL) added while
the temperature was maintained below 25 °C. This was then allowed
to stir at room temperature for ∼4 h. After this time the reaction was
diluted with water (30 mL), and the phases separated. The organic
portion was washed with brine (30 mL), dried (MgSO4), and concen-
trated (in Vacuo) to provide the crude carbamates which were purified
by radical chromatography on silica (EtOAc/hexanes).
1-[[N-Butyl-N-[5-(triethylsilyl)-4-pentenyl]carbamoyl)oxy]-2(1H)-
pyridinethione (37) was obtained as a yellow oil in 74% yield: 1H
NMR δ 0.48-0.68 (m, 6H), 0.88-1.00 (m, 12H), 1.30-1.46 (m, 2H),
1.50-2.00 (m, 4H), 2.10-2.30 (m, 2H), 3.26-3.40 (m, 2H), 3.45-
3.60 (m, 2H), 5.54-5.72 (m, 1H), 5.96-6.12 (m, 1H), 6.61 (t, J ) 6.9
Hz, 1H), 7.17 (t, J ) 7.8 Hz, 1H), 7.58-7.68 (m, 2H); 13C NMR δ
3.23, 7.10, 13.50, 13.56, 19.64, 19.79, 26.22, 27.29, 29.31, 30.46, 33.64,
33.69, 46.90, 47.52, 48.42, 48.64, 111.93, 126.57, 126.82, 133.18,
136.74, 138.50, 138.53, 146.60, 146.73, 151.33, 176.07; MS m/z 408
(M•+, 2), 282 (81), 252 (28), 126 (100), 115 (33), 111 (26), 87 (76),
86 (28), 83 (20), 58 (62), 56 (25); HRMS for C21H36N2O2SSi, m/z calcd
408.2267, found 408.2272.
1-[(N-Butyl-N-4-hexenylcarbamoyl)oxy]-2(1H)-pyridinethione
(38)was obtained as a yellow oil in 34% yield: 1H NMR δ 0.88-1.02
(m, 3H), 1.25-1.48 (m, 2H), 1.54-1.88 (m, 7H), 1.96-2.16 (m, 2H),
3.27-3.39 (m, 2H), 3.45-3.57 (m, 2H), 5.35-5.55 (m, 2H), 6.56-
6.63 (m, 1H), 7.14-7.21 (m, 1H), 7.60-7.69 (m, 2H); 13C NMR δ
13.71, 13.77, 17.83, 19.86, 20.00, 27.21, 28.39, 29.52, 29.62, 29.78,
30.70, 47.35, 47.64, 48.67, 48.86, 112.09, 121.61, 125.68, 125.82,
129.91, 129.99, 133.33, 137.06, 138.70, 151.58, 176.32; MS m/z 308
(M•+, 1), 182 (30), 126 (45), 78 (25), 56 (37), 54 (100); HRMS for
C16H24N2O2S, m/z calcd 308.1558, found 308.1555.
N-Butyl-2-[(triethylsilyl)methyl]pyrrolidine (43) was obtained as
a colorless oil in 81% yield after distillation (82 °C, 0.1 mmHg): 1H
NMR δ 0.40-0.65 (m, 8H), 0.85-1.00 (m, 12H), 1.20-2.40 (m, 11H),
2.80-3.00 (m, 1H), 3.10-3.22 (m, 1H); 13C NMR δ 3.87, 7.37, 14.03,
16.09, 21.02, 21.55, 30.92, 32.63, 53.22, 53.66, 62.16; MS m/z 255
(M•+, 3), 126 (100), 115 (30), 87 (19), 69 (22), 58 (20), 57 (26), 56
(25), 54 (29); HRMS for C15H33NSi, m/z calcd 255.2382, found
255.2372.
1-[[N-Butyl-N-(5-phenyl-4-pentenyl)carbamoyl]oxy]-2(1H)-py-
ridinethione (39) was obtained as a yellow oil in 74% yield: 1H NMR
δ 0.88-1.02 (m, 3H), 1.28-1.46 (m, 2H), 1.54-2.04 (m, 4H), 2.30
N-Butyl-2-ethylpyrrolidine (44) was obtained as a colorless oil in
61% yield after distillation (80 °C, 10 mmHg): 1H NMR δ 0.88 (t, J

Cyclization of N-Butyl-4-pentenylaminyl
J. Am. Chem. Soc., Vol. 118, No. 18, 1996 4283
) 7.5 Hz, 3H), 0.92 (t, J ) 7.2 Hz, 3H), 1.10-1.60 (m, 6H), 1.60-
1.82 (m, 3H), 1.82-2.18 (m, 4H), 2.72-2.86 (m, 1H), 3.12-3.23 (m,
1H); 13C NMR δ 10.81, 14.05, 20.97, 21.91, 26.76, 29.93, 30.89, 54.30,
54.51, 66.73; MS m/z 155 (M•+, 5), 126 (100), 112 (28), 70 (31); HRMS
for C10H21N, m/z calcd 155.1674, found 155.1675.
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 (Bu3-
Sn)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.
N-Butyl-2-benzylpyrrolidine (45) was obtained as a colorless oil
in 86% yield after distillation (93 °C, 0.05 mmHg): 1H NMR δ 0.94
(t, J ) 7.3 Hz, 3H), 1.25-1.85 (m, 8H), 2.05-2.20 (m, 2H), 2.36-
2.54 (m, 2H), 2.82-2.95 (m, 1H), 2.98-3.11 (m, 1H), 3.14-3.24 (m,
1H), 7.14-7.32 (m, 5H); 13C NMR δ 14.06, 20.91, 21.87, 30.36, 31.01,
40.96, 54.14, 54.56, 66.43, 125.78, 128.12, 129.11, 140.20; MS m/z
174 (M•+ - C3H7, 5), 126 (85), 91 (100), 84 (29), 70 (68), 65 (34), 54
(36); HRMS for C12H16N, m/z calcd 174.1283, found 174.1283.
General Procedure for the Reaction of Sulfenamides 3, 4, 6, 7,
and 8 with 1 equiv of Bu3SnH. The appropriate sulfenamide, 2,2′-
azoisobutyronitrile (AIBN), and nonane (GC standard) were added to
a dry 10 mL two-necked round bottom flask, equipped with a magnetic
stir bar, reflux condenser, nitrogen inlet, and rubber septum. Benzene
was then added by syringe and the mixture heated to reflux for ca. 5
min to remove any oxygen from the system, whereupon tributyltin
hydride (1.1 equiv) was added by syringe. After designated intervals
aliquots were removed, diluted with diethyl ether, and analyzed by gas
chromatography.
Kinetic Methods. The appropriate sulfenamide, AIBN, and nonane
were weighed into a 10 mL volumetric flask which was then capped
with a rubber septum and flushed with nitrogen. Bu3SnH (10 equiv)
was added by syringe and the flask made up to the mark with benzene.
A portion of this standard solution (between 0.05 and 2 mL) was then
added by syringe to a Pyrex tube under nitrogen. This was then
followed by addition of the appropriate amount of benzene to dilute
the sample up to 2 mL. The sample was then degassed by the freeze-
pump-thaw method and sealed under vacuum. Using this technique,
up to 10 samples of different concentrations were prepared from a single
standard solution in a couple of hours. These reaction vessels were
then placed in a thermostated oil bath and heated for 3 h (>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
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
t
Bu2SnCl2 (34 mg) (B), Bu2SnClOSnClnBu2 (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), (Ph3-
Sn)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.
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
JA953720S
(34) Otera, J.; Dan-oh, N.; Nozaki, H. J. Org. Chem. 1991, 56, 5307.