Generation and cyclization of unsaturated carbamoyl radicals derived from S-4-pentynyl carbamothioates under tin-free conditions

Article abstract of DOI:10.1021/jo0602064

The radical reaction of benzenethiol with S-4-pentynyl carbamothioates provides a valuable protocol for the tin-free generation of carbamoyl radicals, which arise from intramolecular substitution at sulfur by the initial sulfanylvinyl radicals. This procedure can be usefully employed to achieve N-benzylcarbamoyl radical 5-exo and 4-exo cyclizations leading, respectively, to pyrrolidinones and azetidinones, although, for the latter, it seems of lesser utility. Novel evidence is presented that. N-tosyl-substituted carbamoyl radicals display a peculiar tendency to yield the corresponding isocyanate by β-elimination of the tosyl radical.

Full text of DOI:10.1021/jo0602064

Generation and Cyclization of Unsaturated Carbamoyl Radicals
Derived from S-4-Pentynyl Carbamothioates under Tin-Free
Conditions
Luisa Benati,* Giorgio Bencivenni, Rino Leardini, Matteo Minozzi, Daniele Nanni,
Rosanna Scialpi,* Piero Spagnolo,* and Giuseppe Zanardi
Dipartimento di Chimica Organica “A. Mangini”, UniVersita` di Bologna, Viale Risorgimento 4,
I-40136 Bologna, Italy
spagnolo@ms.fci.unibo.it
ReceiVed January 31, 2006
The radical reaction of benzenethiol with S-4-pentynyl carbamothioates provides a valuable protocol for
the tin-free generation of carbamoyl radicals, which arise from intramolecular substitution at sulfur by
the initial sulfanylvinyl radicals. This procedure can be usefully employed to achieve N-benzylcarbamoyl
radical 5-exo and 4-exo cyclizations leading, respectively, to pyrrolidinones and azetidinones, although,
for the latter, it seems of lesser utility. Novel evidence is presented that N-tosyl-substituted carbamoyl
radicals display a peculiar tendency to yield the corresponding isocyanate by â-elimination of the tosyl
radical.
Introduction
the synthesis of cyclic ketones through cyclization of the acyl
radicals onto suitably placed alkenyl substituents.2h In a
subsequent study, our procedure became a new synthetic method
for the reduction of carboxylic acids to aromatic and aliphatic
aldehydes under radical conditions.4 During this study, we
happened to observe that the S-4-pentynyl derivative of N-
methyl-N-phenylcarbamothioic acid reacted nicely with ben-
zenethiol to yield N-methylformanilide in fairly high yield. This
The use of radical reactions in modern synthetic chemistry
is now well-established.1 Organotin compounds, in particular,
have found widespread application in many types of radical
processes. However, tin-based radical chemistry suffers from
many drawbacks, namely toxicity, hazardous handling, and
difficult removal of tin residues from the final reaction mixtures.
Therefore, a major area of current research is the development
of processes that seek to either alleviate the problems associated
with tin residues or remove the need for tin completely.2
(2) For recent papers on this subject, see: (a) Baguley, P. A.; Walton, J.
C. Angew. Chem., Int. Ed. 1998, 37, 3072. (b) Gagosz, F.; Moutrille, C.;
Zard, S. Z. Org. Lett. 2002, 4, 2707. (c) Kim, S.; Lim, C. J. Angew. Chem.,
Int. Ed. 2002, 41, 3265. (d) Gagosz, F.; Zard, S. Z. Org. Lett. 2002, 4,
4345. (e) Kim, S.; Song, H.-J. Synlett 2002, 12, 2110. (f) Studer, A.; Amrein,
S. Synthesis 2002, 835. (g) Ouvry, G.; Zard, S. Z. Chem. Commun. 2003,
6, 778. (h) Benati, L.; Calestani, G.; Leardini, R.; Minozzi, M.; Nanni, D.;
Spagnolo, P.; Strazzari, S. Org. Lett. 2003, 5, 1313. (i) Boivin, J.; Jrad, R.;
Juge, S.; Nguyen, V. T. Org. Lett. 2003, 5, 1645. (j) Schaffner, A.-P.;
Renaud, P. Angew. Chem., Int. Ed. 2003, 42, 2658. (k) Osornio, Y. M.;
Cruz-Almanza, R.; Jimenez-Montano, V.; Miranda, L. D. Chem. Commun.
2003, 2316. (l) Studer, A.; Amrein, S.; Schleth, F.; Schulte, T.; Walton, J.
C. J. Am. Chem. Soc. 2003, 125, 5726. (m) Studer, A. Chem. Soc. ReV.
2004, 33, 267. (n) Benati, L.; Leardini, R.; Minozzi, M.; Nanni, D.; Scialpi,
R.; Spagnolo, P.; Strazzari, S.; Zanardi, G. Angew. Chem., Int. Ed. 2004,
43, 3598. (o) Molawi, K.; Schulte, T.; Siegenthaler, K. O.; Wetter, C.;
Studer, A. Chem. Eur. J. 2005, 11, 2335.
In a previous work, we have devised a novel method for the
generation of acyl radicals under reducing tin-free conditions
by using readily available 4-pentynylthiol esters in combination
with benzenethiol.2h Indeed, the radical addition of PhSH to
the terminal triple bond of these thiol esters results in intermedi-
ate sulfanylvinyl radicals that are highly capable of performing
intramolecular substitution at sulfur to yield a cyclized 2-alkyl-
idenetetrahydrothiophene with concomitant release of acyl
radicals. Acyl radicals had been previously generated by a
similar substitution process of aryl radicals at the sulfur atom
of thiol esters.3 Our protocol has been successfully applied to
(3) (a) Crich, D.; Yao, Q. J. Org. Chem. 1996, 61, 3566. (b) Crich, D.;
Hao, X. J. Org. Chem. 1997, 62, 5982.
(4) Benati, L.; Leardini, R.; Minozzi, M.; Nanni, D.; Scialpi, R.;
Spagnolo, P.; Zanardi, G. Synlett 2004, 6, 987.
(1) For a comprehensive review on synthetic radical chemistry, see:
Radicals in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.; Wiley-VCH:
Weinheim, 2001; Vols. 1 and 2.
10.1021/jo0602064 CCC: $33.50 © 2006 American Chemical Society
Published on Web 03/21/2006
3192
J. Org. Chem. 2006, 71, 3192-3197

Carbamoyl Radicals DeriVed from S-4-Pentynyl Carbamothioates
SCHEME 1
SCHEME 2
finding revealed that S-4-pentynyl carbamothioates might be
promising precursors of aminoacyl (carbamoyl) radicals. On this
basis, we were prompted to prepare a variety of novel unsatur-
ated N-benzyl- and N-tosyl-substituted carbamothioates 1 with
the aim of producing the corresponding carbamoyl radicals 2
(and the accompanying tetrahydrothiophene 3) upon radical
reaction with benzenethiol (Scheme 1). A proper choice of
unsaturated substrates was made to ascertain whether, in the
presence of the electrophilic thiol H-donor, those nucleophilic
radical species might successfully undergo intramolecular
cyclization onto the internal alkene to give four- and/or five-
membered ring lactam products.5
Several free-radical mediated syntheses of lactams have been
previously reported. Among these, we can mention the organotin
hydride promoted cyclizations of unsaturated R-haloamides,
which have been applied in particular to the synthesis of PS-5
and thienamycin;6 the 4-exo cyclizations of carbamoylcobalt
salophens7a,b and the Mn(III)/Ce(IV)-promoted cyclizations of
enamides, both yielding â-lactams;7c and the TMS3SiH- or Bu3-
SnH-mediated 5-exo cyclizations of selenocarbamates, affording
moderate yields of γ-lactams.8 The early radical synthesis of
lactams either suffered from poor yields or often employed toxic
organotin reagents. However, â- and/or γ-lactams have been
very recently produced in appealing yields under tin-free
conditions via ring closures of unsaturated N-benzylcarbamoyl
radicals derived from both thermal fragmentation of 1-carbam-
oyl-1-methylcyclohexa-2,5-dienes in the presence of radical
initiators9 and photochemical homolysis of oxime oxalate
amides.10 Moreover, efficient production of dithiocarbamoyl
derivatives of â-, γ-, and δ-lactams has been very recently
achieved through group transfer cyclization of N-benzylcar-
bamoyl radicals arising from N,N-diethyldithiocarbamate pre-
cursors upon heating in the presence of dilauroyl peroxide or
alternative irradiation.11
Results and Discussion
The requisite pentynyl carbamothioates 1 were usually
prepared in moderate to good yields by reacting the appropriate
carbamoyl chlorides with 4-pentyne-1-thiol in the presence of
DMAP by an adaptation of the procedure previously employed
for the preparation of our pentynyl carbothioates.2h,4 Their
radical reactions were normally performed by adding a toluene
solution of PhSH (1.1 mmol) over ca. 4 h to a refluxing toluene
solution of the appropriate substrate (1 mmol) and ACCN (1,1′-
azo-bis-cyclohexane-1-carbonitrile) initiator (0.3 mmol) under
a nitrogen atmosphere. The resulting mixture was further
refluxed until virtual disappearance of the starting material (3-6
h) and then separated by column chromatography.
We first examined the generation of carbamoyl radicals that
could lead to pyrrolidinones through 5-exo cyclization onto
suitable alkenylic moieties. The reaction of N-benzyl-N-3-
butenylcarbamothioate 1a smoothly afforded the expected
2-methylidenetrahydrothiophene 3 as a mixture of (E)- and (Z)-
isomers, and the associated carbamoyl radical 2a, which
provided a fairly good yield of the desired pyrrolidinone 4a.
However, compound 4a was accompanied by a significant
amount of the butenylformamide 5a, arising from hydrogen
abstraction of radical 2a from the thiol (Scheme 2).
Comparable efficiency was observed for the production of
carbamoyl radicals 2b-d from the corresponding N-benzyl-N-
(2-alkenylphenyl)carbamothioates 1b-d. Radicals 2b-d, how-
ever, unlike their congener 1a, did not undergo reduction by
benzenethiol but exhibited exclusive ring closure onto the
internal alkene. Indeed, carbamoyl radical 2b only furnished
the cyclized indolinone 6b in good yield, whereas the congener
2c, besides affording a comparable amount of the corresponding
indolinone 6c, also gave minor amounts of the six-membered
ring quinolinone 7. In the latter case, the additional formation
of the formal 6-endo cyclization product 7 was presumably
caused by the intermediate occurrence of a highly stabilized,
tertiary benzylic radical.12 Moreover, carbamoyl radical 2d
afforded the sole indolinone 6d in a slightly enhanced yield, its
5-exo cyclization being probably encouraged by the presence
of the adjacent electron-deficient alkene (Scheme 3).
(5) N-Substituted carbamoyl radicals are known to exist as mixtures of
the respective E- and Z-conformers; see: Sutcliffe, R.; Ingold, K. U. J.
Am. Chem. Soc. 1981, 103, 7686. The predominance of rotamers unfavorable
to ring formation in secondary carbamoyl radicals is a possible reason for
the known reluctance of these radicals to undergo cyclization onto alkenes;
see refs 8 and 9a.
(6) (a) Ishibashi, H.; Kameoka, C.; Iriyama, H.; Kodama, K.; Sato, T.;
Ikeda, M. J. Org. Chem. 1995, 60, 1276. (b) Ishibashi, H.; Kameoka, C.;
Kodama, K.; Sato, T.; Ikeda, M. Tetrahedron 1996, 52, 489.
(7) (a) Gill, G. B.; Pattenden, G.; Reynolds, S. J. J. Chem. Soc., Perkin
Trans. 1 1994, 369. (b) Pattenden, G.; Reynolds, S. J. J. Chem. Soc., Perkin
Trans. 1 1994, 379. (c) D’Annibale, A.; Nanni, D.; Trogolo, C.; Umani, F.
Org. Lett. 2000, 2, 401 and refs cited therein.
(8) Rigby, J. H.; Danca, D. M.; Horner, H. Tetrahedron Lett. 1998, 39,
8413.
(9) (a) Bella, A. F.; Jackson, L. V.; Walton, J. C. Org. Biomol. Chem.
2004, 2, 421. (b) Bella, A. F.; Slawin, A. M. Z.; Walton, J. C. J. Org.
Chem. 2004, 69, 5926. (c) Bella, A. F.; Jackson, L. V.; Walton, J. C. J.
Chem. Soc., Perkin Trans. 2 2002, 1839. (d) Jackson, L. V.; Walton, J. C.
Chem. Commun. 2000, 2327.
(11) Grainger, R. S.; Innocenti, P. Angew. Chem., Int. Ed. 2004, 43, 3443.
(12) In principle, a formally 6-endo-cyclized benzylic radical might result
from ring expansion of the initial 5-exo ring-closed â-oxoindolinylmethyl
radical via 3-exo cyclization onto the adjacent carbonyl group and
subsequent â-scission of the ensuing alkoxyl radical; see: Chatgilialoglu,
C.; Crich, D.; Komatsu, M.; Ryu, J. Chem. ReV. 1999, 99, 1991 and ref 9a.
(10) (a) Scanlan, E. M.; Slawin, A. M. Z.; Walton, J. C. Org. Biomol.
Chem. 2004, 2, 716. (b) Scanlan, E. M.; Walton, J. C. Chem. Commun.
2002, 2086.
J. Org. Chem, Vol. 71, No. 8, 2006 3193

Benati et al.
SCHEME 3
SCHEME 4
SCHEME 5
The above findings therefore revealed that the thiol-mediated
radical reaction of the N-benzylated carbamothioates 1a-d can
serve as a reliable means to generate carbamoyl radicals 2a-
d. Interestingly, the produced radicals 2a-d were usually found
to be highly prone to form cyclized lactams; their concomitant
reduction to formamide, which in principle might have been a
rather crucial side reaction under our reducing conditions, proved
to be a serious limitation only to cyclization of radical 2a.
We next examined the corresponding reactions of compounds
1e-g, i.e., the N-tosyl analogues of carbamothioates 1a-c. We
originally expected that replacement of the benzyl with the
electron-withdrawing tosyl substituent might conceivably de-
press the nucleophilic properties of carbamoyl radicals. Con-
sequently, the N-tosyl carbamoyl radicals 2e-g should have
been more reluctant to undergo reduction by the electrophilic
benzenethiol and hence even more prone to cyclize onto an
electron-rich alkene than the N-benzyl counterparts 2a-c.
Nevertheless, our results with compounds 1e-g unexpectedly
revealed that carbamoyl radicals 2e-g exhibit a peculiar
tendency to undergo â-scission to afford tosyl radical and an
alkenyl/alkenylaryl isocyanate, which, however, in every case
escaped detection. To our knowledge, such a type of radical
process is unprecedented in carbamoyl radical chemistry.13
3, compound 8 could additionally occur by direct addition of
tosyl radical to the alkynylic bond of the starting substrates 1e-
g.17
The usual reaction of compound 1e, besides the two tetrahy-
drothiophenes 3 and 8, gave the tosylated pyrrolidinone 4e
(57%) as the only identifiable product of carbamoyl radical 2e.
Despite the lack of any evidence at all for possible hydrogen
abstraction of radical 2e from the thiol, observed instead with
the N-benzyl counterpart 2a, the outcoming yield of pyrrolidi-
none 4e was lower than that of the analogous compound 4a
obtained from 2a (Schemes 2 and 4). This observation is
consistent with the concomitant disappearance of carbamoyl
radical 2e by the supposed likely elimination of tosyl radical.
In sharp contrast with the N-benzyl analogues 2b,c, the
tosylated radicals 2f,g, generated from carbamothioates 1f,g,
furnished no indolinone products, but gave instead useful yields
of the corresponding quinolinones 9f,g only (Scheme 5).18
Quinolinones 9f,g were probably due to the key intervention
of the intermediate `ısocyanates 10f,g, which under these
circumstances would readily arise from their presumed progeni-
tors 2f,g. Indeed, 2-vinylphenyl isocyanates 10f,g are known
Every reaction of carbamothioates 1e-g furnished the tosy-
lated tetrahydrothiophene 814 in preference to the usual sulfen-
ylated analogue 3, which under these circumstances was formed
only to a limited extent (Schemes 4 and 5). Compound 8 could
plausibly arise from addition of the released tosyl radical to
the activated PhS-substituted ethylene carbon of the initially
formed tetrahydrothiophene 3 followed by â-elimination of
benzenesulfanyl radical from the ensuing carbon-centered
radical.15,16 However, it is more likely that, similar to congener
(13) No evidence for any â-elimination of tosyl radical was gained in
previous cyclization reactions of N-tosylcarbamoyl radicals derived from
corresponding selenocarbamates, see ref 8.
(14) Similar to the analogue 3 (ref 2h), the tosylated tetrahydrothiophene
8 occurred as a mixture of (E)- and (Z)-isomer in unestablished ratio.
(15) The â-elimination of benzenesulfanyl radical from carbon-centered
radicals is faster than that of tosyl radical, see: Timokhin, V. I.; Gastaldi,
S.; Bertrand, M. P.; Chatgilialoglu, C. J. Org. Chem. 2003, 68, 3532.
(16) A control experiment established that tetrahydrothiophene 3 can be
converted to the tosylated analogue 8 upon radical reaction with TsSPh/
AIBN in refluxing benzene.
(17) A control experiment interestingly showed that the radical chain
reaction of S-4-pentynyl benzenecarbothioate with TsSPh/AIBN in refluxing
benzene cleanly afforded compound 8 as well as S-phenyl benzenecarbo-
thioate.
(18) For unclear reasons, the carbamoyl radical 2g could also undergo
significant decarbonylation leading to reduced N-(2-isopropenylphenyl)-4-
methylbenzenesulfonamide (25%).
3194 J. Org. Chem., Vol. 71, No. 8, 2006

Carbamoyl Radicals DeriVed from S-4-Pentynyl Carbamothioates
SCHEME 6
SCHEME 8
SCHEME 7
leading to â-lactams was largely based on the use of nonre-
ductive reaction conditions.9-11
Our first attempt to obtain azetidinone 13h from N-benzyl-
N-allylcarbamothioate 1h was largely frustrating. The usual
reaction of 1h resulted in extensive production of formamide
5h (55%), whereas azetidinone 13h occurred only to a very
poor extent (12%) and was even accompanied by a larger
amount of pyrrolidinone 4h (Scheme 8). Evidently, the ensuing
carbamoyl radical 2h was highly reluctant to undergo 4-exo
cyclization onto the terminal alkene and thus preferred to exhibit
major hydrogen abstraction from the thiol as well as alternative
5-endo cyclization.22
More rewarding results were, however, obtained from the
reactions of N-benzyl-N-2-butenyl-, 1i, and N-benzyl-N-(3-
phenyl-2-propenyl)carbamothioate 1j. In such cases, the azeti-
dinones 13i,j were obtained in noticeably enhanced yields (25-
32%) as the sole cyclized products, although still associated
with important amounts of the concomitant formamides 5i,j
(Scheme 8). Apparently, the resultant carbamoyl radicals 2i,j
exhibited more efficient 4-exo cyclization owing to the enhanced
stabilization provided by the methyl and, especially, the phenyl
substituent to the ring-closed â-oxoazetidinylmethyl radical. An
even more promising result was obtained from our final reaction
with the N-Boc-substituted N-allylcarbamothioate 1k. In contrast
with the N-benzyl analogue 1h, compound 1k furnished a useful
yield (42%) of azetidinone 13k, and no traces of any ac-
companying pyrrolidinone or reduced formamide 5k were
observed (Scheme 8).23 This finding interestingly discovered
that the presence of the electron-withdrawing Boc substituent
on the carbamoyl nitrogen might play a beneficial role in
carbamoyl radical cyclizations onto alkenes.
to smoothly afford quinolinones 9f,g through thermal electro-
cyclization followed by 1,5-H sigmatropic shift (Scheme 5).19
In an attempt to gain direct proof of isocyanate occurrence in
our reactions involving N-tosyl carbamoyl radicals, we also
investigated the behavior of S-4-pentynyl N-tosyl-N-(4-chloro-
phenyl)carbamothioate 11 under our usual conditions (Scheme
6). Unfortunately, compound 11 led to a complex reaction
mixture that failed to reveal the presence of possible 4-chloro-
phenyl isocyanate. However, in addition to modest amounts of
the expected tetrahydrothiophenes 3 and 8, column chromatog-
raphy separated small amounts (3%) of S-phenyl N-(4-chloro-
phenyl)carbamothioate which was the formal product of ben-
zenethiol addition to 4-chlorophenyl isocyanate (Scheme 6).
It is worth noting that the above quinolinone 9g had already
been reported to occur upon cyclization of the same radical 2g,
at that time generated by reacting carbamoyl phenyl selenide
12 with TMS3SiH/AIBN. Lacking any conclusive evidence, the
authors were led to explain the occurrence of 9g in terms of
primary radical 6-endo ring closure followed by extrusion of
tosyl radical from the cyclized benzylic radical (Scheme 7).8
Our present chemical evidence strongly suggests that this
original mechanistic explanation should be essentially rejected.
As we proved that N-benzylcarbamothioates provide a
valuable radical entry to pyrrolidinone compounds,20 we were
finally prompted to attempt extension of our tin-free protocol
to the construction of four-membered ring azetidinones. We
were aware that our reductive protocol might have been less
rewarding for azetidinones in view of the known fact that radical
4-exo ring closures, including those of carbamoyl radicals, are
significantly slower than the 5-exo analogues.21 In fact, the
successful outcome of very recent carbamoyl radical cyclizations
Conclusions
In this work, we have devised a new, valuable tin-free
protocol for the generation of carbamoyl radicals using acces-
sible S-4-pentynyl carbamothioate precursors. The present
procedure can be usefully employed to attain cyclizations of
N-benzylcarbamoyl radicals leading to pyrrolidinones, but it
seems of minor utility for those leading to azetidinones. To
obtain better results with the latter, a crucial role might be played
(19) Luo, L.; Bartberger, M. D.; Dolbier, W. R., Jr. J. Am. Chem. Soc.
1997, 119, 12366.
(20) Comparable yields of pyrrolydinones and indolinones have been
reported in previous cyclizations of N-benzylcarbamoyl radicals derived
from 1-benzylcarbamoyl-1-methylcyclohexa-2,5-dienes; see ref 9a,b. How-
ever, a better yield of pyrrolidinone 4a was achieved when the carbamoyl
radical 2a was generated by UV photolysis of the corresponding oxime
oxalate amide; see ref 10a.
(22) In principle, pyrrolidinone 4h might also arise from ring enlargement
of the initial 4-exo ring-closed â-oxoazetidinylmethyl radical, see ref 12.
(23) Only minor amounts of a mixture of unidentified products were
obtained.
(21) DiLabio, G. A.; Scanlan, E. M.; Walton, J. C. Org. Lett. 2005, 7,
155.
J. Org. Chem, Vol. 71, No. 8, 2006 3195

Benati et al.
1
3290 (≡CH), 1678 (CO); H NMR (300 MHz, CDCl3) δ 1.73-
1.83 (2 H, m), 1.95 (1 H, t, J ) 2.8), 2.24 (2 H, dt, J ) 6.6, 2.8
Hz), 2.44 (3 H, s), 2.50-2.60 (2 H, m), 2.96 (2 H, t, J ) 6.6 Hz),
3.87-3.94 (2 H, m), 5.09-5.21 (2 H, m), 5.76-5.87 (1 H, m),
7.32 (2 H, d, J ) 8.4 Hz), 7.87 (2 H, d, J ) 8.4 Hz); 13C NMR (75
MHz, CDCl3) δ 17.4 (CH2), 21.7, 27.9 (CH2), 29.6 (CH2), 34.4
(CH2), 46.7 (CH2), 69.3, 82.7 (C), 117.9 (CH2), 128.4, 129.4, 133.6,
136.2 (C), 145.1 (C), 168.4 (CO); MS (ESI) 374 (M + Na)+. Anal.
Calcd for C17H21NO3S2: C, 58.09; H, 6.02; N, 3.99. Found: C,
58.01; H, 6.03; N, 4.01.
by N-Boc substituent. In this work, we have additionally shown
that N-tosylated carbamoyl radicals have a peculiar tendency
to form the corresponding isocyanate by â-elimination of tosyl
radical. The peculiar behavior of N-tosyl-N-(2-vinylphenyl)-
carbamoyl radicals might be exploited for the construction of
quinolinone ring systems.
Experimental Section
Physical and analytical data for the new pentynyl carbamothioates
1a-k and 11 are as follows:24
S-(4-Pentynyl) N-(2-vinylphenyl)-N-[(4-methylphenyl)sulfon-
yl]carbamothioate (1f): oil; IR (CHCl3) νmax (cm-1) 3293 (≡CH),
1
S-(4-Pentynyl) N-benzyl-N-(3-butenyl)carbamothioate (1a):
1682 (CO); H NMR (300 MHz, CDCl3) δ 1.66-1.76 (2 H, m),
1
oil; IR (CHCl3) νmax (cm-1) 3298 (≡CH), 1648 (CO); H NMR
1.89 (1 H, t, J ) 2.6 Hz), 2.15 (2 H, dt, J ) 2.6, 7.0 Hz), 2.46 (3
H, s), 2.75-2.92 (2 H, m), 5.41 (1 H, dd, J ) 0.9, 11.0 Hz), 5.90
(1 H, dd, J ) 0.9, 17.4 Hz), 6.79 (1 H, dd, J ) 11.0, 17.4 Hz),
7.20 (1 H, d, J ) 8.1 Hz), 7.21-7.43 (3 H, m), 7.50 (1 H, t, J )
(300 MHz, CDCl3) δ 1.83-1.93 (2 H, m), 1.97 (1 H, t, J ) 2.7
Hz), 2.24-2.36 (4 H, m), 3.05 (2 H, t, J ) 7.2 Hz), 3.26-3.47 (2
H, br s), 4.52-4.67 (2 H, m), 4.98-5.10 (2 H, m), 5.66-5.80 (1
H, m), 7.20-7.38 (5 H, m); 13C NMR (75 MHz, CDCl3) δ 17.4
(CH2), 28.8 (CH2), 29.3 (CH2), 32.2 (CH2), 46.6 (CH2), 50.1 (CH2),
51.4 (CH2), 69.0, 83.2 (C), 116.9 (CH2), 117.2 (CH2), 127.1, 127.4,
127.7, 128.5, 134.3 (C), 134.8 (C), 168.0 (CO); MS (ESI) 310
(M + Na)+. Anal. Calcd for C17H21NOS: C, 71.04; H, 7.36; N,
4.87. Found: C, 71.07; H, 7.34; N, 4.86.
7.2 Hz), 7.72 (1 H, d, J ) 7.7 Hz), 7.96 (2 H, d, J ) 8.5 Hz); 13
C
NMR (75 MHz, CDCl3) δ 17.3 (CH2), 21.7 (CH3), 27.8 (CH2),
30.1 (CH2), 69.1, 82.7 (C), 117.9 (CH2), 126.2, 128.7, 129.0, 129.3,
131.0, 131.2, 131.4, 132.0 (C), 135.7 (C), 138.9 (C), 145.3 (C),
169.1 (CO); MS (ESI) 422 (M + Na)+. Anal. Calcd for C21H21-
NO3S2: C, 63.13; H, 5.30; N, 3.51. Found: C, 63.10; H, 5.31; N,
3.50.
S-(4-Pentynyl) N-benzyl-N-(2-vinylphenyl)carbamothioate (1b):
oil; IR (neat) νmax (cm-1) 3297 (≡CH), 1654 (CO); 1H NMR (300
MHz, CDCl3) δ 1.75-1.86 (2 H, m), 1.93 (1 H, t, J ) 2.7 Hz),
2.24 (2 H, dt, J ) 2.7, 6.9 Hz), 2.95 (2 H, m), 4.24 (1 H, d, J )
14.2 Hz), 5.31 (1 H, dd, J ) 1.1, 11.1 Hz), 5.36 (1 H, d, J ) 14.2
Hz), 5.75 (1 H, dd, J ) 1.1, 17.4 Hz), 6.63 (1 H, dd, J ) 11.1,
17.4 Hz), 6.81 (1 H, dd, J ) 1.2, 7.9 Hz), 7.17 (3 H, m), 7.25 (3
H, m), 7.35 (1 H, m), 7.62 (1 H, dd, J ) 1.2, 7.9 Hz); 13C NMR
(75 MHz, CDCl3) δ 17.4 (CH2), 28.8 (CH2), 29.9 (CH2), 53.8 (CH2),
68.8, 83.3 (C), 116.8 (CH2), 126.2, 126.4, 127.6, 128.4, 129.3,
131.1, 131.5, 136.5 (C), 136.6 (C), 137. 2 (C), 169.1 (CO); MS
(ESI) 359 (M + Na)+. Anal. Calcd for C21H21NOS: C, 75.19; H,
6.31; N, 4.18. Found: C, 75.22; H, 6.30; N, 4.20.
S-(4-Pentynyl) N-benzyl-N-(2-isopropenylphenyl)carbamo-
thioate (1c): oil; IR (CHCl3) νmax (cm-1) 3307 (≡CH), 1649 (CO);
1H NMR (300 MHz, CDCl3) δ 1.74-1.85 (2 H, m), 1.91 (1 H, t,
J ) 2.7 Hz), 2.12 (3 H, s), 2.23 (2 H, dt, J ) 2.7, 7.1 Hz), 2.83-
3.06 (2 H, m), 3.96 (1 H, d, J ) 14.4 Hz), 5.16-5.24 (2 H, m),
5.55 (1 H, d, J ) 14.4 Hz), 6.81 (1 H, d, J ) 7.9 Hz), 7.06-7.20
(3 H, m), 7.21-7.28 (3 H, m), 7.30-7.32 (2 H, m); 13C NMR (75
MHz, CDCl3) δ 17.5 (CH2), 23.2, 28.9 (CH2), 29.9 (CH2), 53.0
(CH2), 68.8, 83.3 (C), 116.8 (CH2), 127.3, 127.4, 128.3, 128.9,
128.9, 129.8, 131.9, 136.4 (C), 136.8 (C), 142.3 (C), 142.9 (C),
169.1 (CO). Anal. Calcd for C22H23NOS: C, 75.61; H, 6.63; N,
4.01. Found: C, 75.58; H, 6.62; N, 4.02.
S-(4-Pentynyl) N-(2-isopropenylphenyl)-N-[(4-methylphenyl)-
sulfonyl]carbamothioate (1g): solid; mp 78-79 °C; IR (CHCl3)
ν
max (cm-1) 3308 (≡CH), 1676 (CO); 1H NMR (300 MHz, CDCl3)
δ 1.66-1.78 (2 H, m), 1.90 (1 H, t, J ) 2.8 Hz), 2.13-2.20 (2 H,
m), 2.18 (3 H, s), 2.58 (3 H, s), 2.74-2.96 (2 H, m), 5.24-5.28 (1
H, m), 5.29-5.32 (1 H, m), 7.16 (1 H, dd, J ) 1.2, 7.7 Hz), 7.30-
7.66 (5 H, m), 7.96(2 H, d, J ) 8.5 Hz); 7.13-7. 13C NMR (75
MHz, CDCl3) δ 17.5 (CH2), 21.8, 24.0, 28.1 (CH2), 30.3 (CH2),
69.3, 82.9 (C), 117.1 (C), 117.8 (CH2), 120.6, 124.4, 127.3, 128.0,
129.3, 129.6, 130.1, 130.9, 131.3, 136.2 (C), 141.7 (C), 145.1 (C),
145.9 (C), 169.5 (CO); MS (ESI) 436 (M + Na)+. Anal. Calcd for
C22H23NO3S2: C, 63.89; H, 5.61; N, 3.39. Found: C, 63.95; H,
5.62; N, 3.40.
S-(4-Pentynyl) N-allyl-N-benzylcarbamothioate (1h): oil; IR
(CHCl3) νmax (cm-1) 3305 (≡CH), 1694 (CO); 1H NMR (300 MHz,
CDCl3) δ 1.83-1.93 (2 H, m), 1.97 (1 H, t, J ) 2.7 Hz), 2.32 (2
H, dt, J ) 2.6, 7.0 Hz), 3.07 (2 H, t, J ) 7.0 Hz), 3.91(2 H, br s),
4.57 (2 H, s), 5.08-5.26 (2 H, m), 5.75 (1 H, ddt, J ) 5.7, 10.2,
17.1 Hz), 7.21-7.38 (5 H, m); 13C NMR (75 MHz, CDCl3) δ 17.4
(CH2), 28.8 (CH2), 29.3 (CH2), 33.2 (CH2), 49.0 (CH2), 69.8, 83.2
(C), 117.8 (CH2), 127.4, 127.9, 128.5, 132.1, 168.1 (CO) (the
quaternary aromatic carbon was hidden); MS (ESI) 296 (M + Na)+.
Anal. Calcd for C16H19NOS: C, 70.29; H, 7.00; N, 5.12. Found:
C, 70.31; H, 6.99; N, 5.13.
Ethyl (E)-3-(2-{benzyl[(4-pentynylsulfanyl)carbonyl]amino}-
phenyl)-2-propenoate (1d): oil; IR (neat) νmax (cm-1) 3297 (≡CH),
1729 (CO), 1713 (CO); 1H NMR (300 MHz, CDCl3) δ 1.32 (3 H,
t, J ) 7.1 Hz), 1.74-1.86 (2 H, m), 1.92 (1 H, t, J ) 2.8 Hz), 2.23
(2 H, dt, J ) 2.8, 7.1 Hz), 2.87-3.05 (2 H, m), 4.24 (2 H, q, J )
7.1 Hz), 4.54 (1 H, d, J ) 14.5 Hz), 5.14 (1 H, d, J ) 14.5 Hz),
6.31 (1 H, d, J ) 15.8 Hz), 6.94 (1 H, dd, J ) 1.6, 7.9 Hz), 7.13-
7.18 (2 H, m), 7.22-7.26 (3 H, m), 7.31 (1 H, dt, J ) 1.6, 7.7 Hz),
7.39 (1 H, dt, J ) 1.1, 7.7 Hz), 7.47 (1 H, d, J ) 15.8 Hz), 7.63
(1 H, dd, J ) 1.6, 7.9 Hz); 13C NMR (75 MHz, CDCl3) δ 13.7,
16.8 (CH2), 28.5 (CH2), 29.4 (CH2), 53.8 (CH2), 59.8 (CH2), 68.5,
82.5 (C), 120.3, 126.8, 127.3, 127.9, 128.9, 130.2, 130.9 (C), 133.8
(C), 135.7 (C), 138.4, 165.5 (CO), 168.4 (CO). Anal. Calcd for
C24H25NO3S: C, 70.73; H, 6.18; N, 3.44. Found: C, 70.76; H, 6.19;
N, 3.45.
S-(4-Pentynyl) N-benzyl-N-2-butenylcarbamothioate (1i): oily
mixture of the cis/trans isomers; IR (CHCl3) νmax (cm-1) 3297
(≡CH), 1651 (CO); 1H NMR (300 MHz, CDCl3 ) d 1.70 (3 H, br
d, J ) 5.8 Hz), 1.84-1.94 (2 H, m), 1.98 (1 H, t, J ) 2.5 Hz),
2.32 (2 H, dt, J ) 2.5, 6.9 Hz), 3.06 (2 H, t, J ) 6.9 Hz), 3.76-
3.93 (2 H, m), 4.56 (2 H, br s), 5.34-5.44 (1 H, m), 5.56 (1 H, br
s), 7.21-7.38 (5 H, m); 13C NMR (75 MHz, CDCl3) d 17.2 (CH2),
17.3, 28.7 (CH2), 29.0 (CH2), 36.9 (CH2), 47.8 (CH2), 48.7 (CH2),
68.8, 82.9 (C), 124.6, 127.1, 127.7, 128.0, 128.2, 129.3, 135.9 (C),
136.7 (C), 167.5 (CO); MS (ESI) 310 (M + Na)+. Anal. Calcd for
C17H21NOS: C, 71.04; H, 7.36; N, 4.87. Found: C, 71.07; H, 7.35;
N, 4.88.
S-(4-Pentynyl) N-benzyl-N-[(E)-3-phenyl-2-propenyl]carbam-
othioate (1j): oil; IR (CHCl3) νmax (cm-1) 3295 (≡CH), 1648 (CÃ);
1H NMR (300 MHz, CDCl3 ) d 1.86-1.96 (2 H, m), 1.98 (1 H, t,
J ) 2.5 Hz), 2.32 (2 H, dt, J ) 2.5, 7.1 Hz), 3.10 (2 H, t, J ) 7.1
Hz), 4.08 (2 H, br s), 4.62 (2 H, br s), 6.10 (1 H, dt, J ) 6.3, 16.4
Hz), 6.44 (1 H, br d, J ) 16.4 Hz), 7.22-7.38 (10 H, m); 13C
NMR (75 MHz, CDCl3) d 17.5 (CH2), 28.9 (CH2), 29.4 (CH2),
48.3 (CH2), 65.9 (CH2), 69.0, 83.2 (C), 123.6, 126.4, 127.3 (C),
127.5, 127.8, 128.5, 128.6, 133.2, 136.2 (C), 168.2 (CO); MS (ESI)
S-(4-Pentynyl) N-3-butenyl-N-[(4-methylphenyl)sulfonyl]car-
bamothioate (1e): solid; mp 40-41 °C; IR (CHCl3) νmax (cm-1
)
(24) Owing to slow rotation around the carbonyl carbon-nitrogen bond,
carbamothioate carbons near to nitrogen usually showed broad or split
signals in the 13C NMR spectra.
3196 J. Org. Chem., Vol. 71, No. 8, 2006

Carbamoyl Radicals DeriVed from S-4-Pentynyl Carbamothioates
372 (M + Na)+. Anal. Calcd for C22H23NOS: C, 75.61; H, 6.63;
N, 4.01. Found: C, 75.58; H, 6.64; N, 4.00.
(2 H, d, J ) 8.3 Hz), 7.76 (2 H, d, J ) 8.3 Hz); 13C NMR (75
MHz, CDCl3) δ 22.3, 30.4 (CH2), 34.7 (CH2), 35.2 (CH2), 115.8,
127.6, 130.4, 140.5 (C), 144.4 (C), 167.4 (C); HRMS (m/z, M+)
calcd for C12H14S2O2 254.04353, found 254.04374. Anal. Calcd
for C12H14O2S2: C, 56.66; H, 5.55. Found: C, 56.80; H, 5.56.
Dihydro-(Z)-2(3H)-thiophenylidenemethyl 4-methylphenyl sul-
fone [(Z)-8]:25 solid; mp 199-200 °C;1H NMR (300 MHz, CDCl3)
δ 2.07 (2 H, m), 2.43 (3 H, s), 2.75 (2 H, dt, Jd ) 1.4 Hz, Jt )7.0
Hz), 3.11 (2 H, t, J ) 6.4 Hz), 6.25 (1 H, t, J ) 1.4 Hz), 7.31 (2
H, d, J ) 8.2 Hz), 7.84 (2 H, d, J ) 8.2 Hz); 13C NMR (75 MHz,
CDCl3) δ 22.3, 28.8 (CH2), 36.3 (CH2), 40.8 (CH2), 115.8, 127.8,
130.3, 140.0 (C), 144.5 (C), 165.3 (C); HRMS (m/z, M+) calcd for
C12H14S2O2 254.04353, found 254.04352. Anal. Calcd for C12H14-
O2S2: C, 56.66; H, 5.55. Found: C, 56.82; H, 5.58.
tert-Butyl 3-methyl-2-oxo-1-azetanecarboxylate (13k): oil; IR
(CHCl3) νmax (cm-1) 1804 (CO), 1718 (CO); 1H NMR (300 MHz,
CDCl3) δ 1.35 (3 H, d, J ) 7.1 Hz), 1.53 (9 H, s), 3.18-3.29 (2
H, m), 3.68-3.74 (1 H, m); 13C NMR (75 MHz, CDCl3) δ 13.5,
28.0, 43.9, 45.7 (CH2), 83.4 (C), 148.2 (CO), 168.5 (CO); MS (ESI)
208 (M + Na)+. Anal. Calcd for C9H15NO3: C, 58.36; H, 8.17; N,
7.57. Found: C, 58.31; H, 8.18; N, 7.60.
5-({[Allyl(tert-butoxycarbonyl)amino]carbonyl}sulfanyl)-1-
pentyne (1k): oil; IR (CHCl3) νmax (cm-1) 3294 (≡CH), 1656 (CO);
1H NMR (300 MHz, CDCl3) d 1.53 (9 H, s), 1.80-1.92 (2 H, m),
1.97 (1 H, t, J ) 2.5 Hz), 2.32 (2 H, dt, J ) 2.5, 6.8 Hz), 2.96 (2
H, t, J ) 7.4 Hz), 4.34 (2 H, dt, J ) 1.5, 5.6 Hz), 5.07-5.21(2 H,
m), 5.80 (1 H, ddt, J ) 5.6, 5.8, 10.3 Hz); 13C NMR (75 MHz,
CDCl3) d 17.6 (CH2), 27.8 (CH2), 27.9, 29.6 (CH2), 47.5 (CH2),
68.9, 83.1 (C), 83.8 (C), 116.7, 132.7 (CH2), 152.6 (CO), 170.6
(CO); MS (ESI) 306 (M + Na)+. Anal. Calcd for C14H21NO3S: C,
59.34; H, 7.47; N, 4.94. Found: C, 59.36; H, 7.46; N, 4.95.
S-4-Pentynyl N-(4-chlorophenyl)-N-[(4-methylphenyl)sulfon-
yl]carbamothioate (11): solid; mp 112-113 °C; IR (CHCl3) νmax
1
(cm-1) 3308 (≡CH), 1681(CO); H NMR (300 MHz, CDCl3) δ
1.81-1.91 (2 H, m), 1.91 (1 H, t, J ) 2.8 Hz), 2.17 (2 H, dt, J )
2.8, 7.4 Hz), 2.47 (3 H, s), 2.86 (2 H, t, J ) 7.4 Hz), 7.25 (2 H, d,
J ) 8.2 Hz), 7.37 (2 H, d, J ) 8.6 Hz), 7.45 (2 H, d, J ) 8.6 Hz),
7.91 (2 H, d, J ) 8.2 Hz); 13C NMR (75 MHz, CDCl3) δ 17.6
(CH2), 21.7, 28.0 (CH2), 30.5 (CH2), 69.5, 82.7 (C), 129.0, 129.6,
129.8, 132.5, 133.0 (C), 135.7 (C), 137.0 (C), 145.4 (C), 169.1
(CO); MS (ESI) 430 (M + Na)+. Anal. Calcd for C19H18ClNO3S2:
C, 55.94; H, 4.45; N, 3.43. Found: C, 55.90; H, 4.46; N, 3.42.
Physical and analytical data for the new products (E)- and (Z)-8
and 13k were as follows:
Acknowledgment. We gratefully acknowledge financial
support from MIUR (2004-2005 Funds for “Free Radicals in
Oxidation Reactions and in New Synthetic Processes”).
Dihydro-(E)-2(3H)-thiophenylidenemethyl 4-methylphenyl sul-
fone [(E)-8]:25 solid; mp 94-95 °C; 1H NMR (300 MHz, CDCl3)
δ 2.18 (2 H, m), 2.43 (3 H, s), 3.06 (2 H, t, J ) 6.6 Hz), 3.15 (2
H, dt, Jd ) 1.9 Hz, Jt ) 6.6 Hz), 6.26 (1 H, t, J ) 1.9 Hz), 7.30
Supporting Information Available: General remarks; general
synthesis of pentynyl carbamothioates 1a-k and 11; general
procedure for the reactions of carbamothioates 1a-k and 11 with
benzenethiol and table of the results. This material is available free
of charge via the Internet at http://pubs.acs.org.
(25) Configurational assignment to (E)-8a and (Z)-8a was based on the
expectation that the 4J of the vinylic proton with the allylic-like ring protons
should be larger for the (E)- than for the (Z)-isomer; see ref 2h.
JO0602064
J. Org. Chem, Vol. 71, No. 8, 2006 3197