Generation and Cyclization of Acyl Radicals from Thiol Esters under Nonreducing, Tin-Free Conditions

Article abstract of DOI:10.1021/jo970500j

The preparation of 2-(2-((tert-butyloxycarbonyl)amino)phenyl)ethyl mercaptan from 2-(2-aminophenyl)ethanol is described. This thiol is condensed with a series of suitably unsaturated carboxylic acids to give a series of thiol esters. The Boc group is remo

Full text of DOI:10.1021/jo970500j

5982
J . Org. Chem. 1997, 62, 5982-5988
Gen er a tion a n d Cycliza tion of Acyl Ra d ica ls fr om Th iol Ester s
Un d er Non r ed u cin g, Tin -F r ee Con d ition s
David Crich* and Xiaolin Hao
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
Received March 18, 1997X
The preparation of 2-(2-((tert-butyloxycarbonyl)amino)phenyl)ethyl mercaptan from 2-(2-amino-
phenyl)ethanol is described. This thiol is condensed with a series of suitably unsaturated carboxylic
acids to give a series of thiol esters. The Boc group is removed and the amine reacted with isoamyl
nitrite to give a series of diazonium salts. Exposure to iodide in acetone solution then generates
the aryl radical, which undergoes intramolecular homolytic substitution at sulfur with liberation
of the acyl radical. Following acyl radical cyclization, quenching by iodine and then elimination of
HI leads to the isolation of R-methylene cycloalkanones in good yield.
Sch em e 1
Thiol esters are very poor sources of acyl radicals, both
photochemically and in conjunction with standard silanes
and stannanes.1 This lack of reactivity may be overcome,
as we have recently demonstrated,2 by the inclusion of a
simple additional propagation step in which an aryl
radical brings about an intramolecular homolytic sub-
stitution3 at sulfur (Scheme 1).4 In developing this
chemistry, we generated the requisite aryl radical from
the corresponding aryl iodide with tributyltin hydride,
allyltributylstannane, or tris(trimethylsilyl)silane.2 We
next set ourselves the goal of avoiding the use of such
reducing conditions and, in the case of the tin-based
reagents, the attendant problems of purification and
disposal. The answer, we surmised, lay in the use of
arenediazonium ions as convenient precursors to aryl
radicals.
Sch em e 2
Beckwith has elegantly demonstrated that arenedia-
zonium salts function as efficient sources of aryl radicals
when exposed to suitable electron donors, such as iodide
and thiolate anions, and that such chemistry may be
employed in radical cyclization onto alkenes.5-7 In recent
years, Murphy has astutely exploited this means of aryl
radical generation, coupled with the use of tetrathiaful-
vene as electron donor and, via its radical cation,
eventual radical trap in synthesis.8-13 In all of this
chemistry, as in the classical, mechanistically related
Meerwein arylation,14 the arene ring of the aryl radical
necessarily becomes an intimate part of the target
molecule. In the concept set out here, the aryl radical
merely serves as a convenient handle, thus removing the
need to design any synthesis around this nucleus.
We began our study with the synthesis of the crystal-
line thiol 1 (Scheme 2). Reaction of amino alcohol 2 with
Boc2O gave carbamate 3, which was transformed into
mesylate 4 and then to thiol acetate 5 by displacement
with cesium thioacetate.15 Selective reduction of the thiol
ester function provided 1. The overall yield for this
straightforward, four-step protocol was 79%.
Thiol 1 was then condensed with a number of acids,
via the acid chlorides, to give the thiol esters (11-17,
Chart 1) in 77-85% yield (Table 1). The previously
unknown 2-allyl-4-nitrobenzoic acid (8) was readily ob-
tained by Stille coupling16 of commerical methyl 2-bromo-
4-nitrobenzoate (6) with allyltributyltin as illustrated in
Scheme 3. Alkylation of diethyl allylmalonate with tert-
butyl bromoacetate followed by exposure to trifluoroacetic
acid provided the only other new substrate (10) (Scheme
4).
X Abstract published in Advance ACS Abstracts, August 1, 1997.
(1) Crich, D.; Yuan, H. In Advances in Free Radical Chemistry;
Rawal, V. H., Ed.; J ai Press: New York, 1997; Vol. 2, in press.
(2) Crich, D.; Yao, Q. J . Org. Chem. 1996, 61, 3566-3570.
(3) Schiesser, C. H.; Wild, L. M. Tetrahedron 1996, 52, 13265-
13314.
(4) The use of an aryl radical in this displacement is critical to the
achievement of high yields. When a simple alkyl radical is used the
rate constant for the 5-exo-substitution process is too low for efficient
cyclization. Beckwith, A. L. J .; Duggan, S. A. M. J . Chem. Soc., Perkin
Trans. 2 1994, 1509-1518.
(5) Meijs, G. F.; Beckwith, A. L. J . J . Am. Chem. Soc. 1986, 108,
5890-5893.
(6) Beckwith, A. L. J .; Meijs, G. F. J . Org. Chem. 1987, 52, 1922-
1930.
Each ester was exposed to hydrogen chloride in ethyl
acetate leading to removal of the Boc protecting groups
(7) Abeywickrema, A. N.; Beckwith, A. L. J . J . Am. Chem. Soc. 1986,
108, 8227-8229.
(8) Begley, M. J .; Murphy, J . A.; Roome, S. J . Tetrahedron Lett. 1994,
35, 8679-8682.
(12) Lampard, C.; Murphy, J . A.; Rasheed, F.; Lewis, N.; Hurst-
house, M. B.; Hibbs, D. E. Tetrahedron Lett. 1994, 35, 8675-8678.
(13) Murphy, J . A.; Rasheed, F.; Roome, S. J .; Lewis, N. J . Chem.
Soc., Chem. Commun. 1996, 737-738.
(14) Galli, C. Chem. Rev. 1988, 88, 765-792.
(15) Strijtveen, B.; Kellog, R. M. J . Org. Chem. 1986, 51, 3664-
3671.
(9) Fletcher, P. J .; Hibbs, D. E.; Hursthouse, M.; Lampard, C.;
Murphy, J . A.; Roome, S. J . J . Chem. Soc., Chem. Commun. 1996, 739-
740.
(10) Kizil, M.; Murphy, J . A. J . Chem. Soc., Chem. Commun. 1995,
1409-1410.
(11) Kizil, M.; Lampard, C.; Murphy, J . A. Tetrahedron Lett. 1996,
37, 2511-2514.
(16) Stille, J . K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508-524.
S0022-3263(97)00500-8 CCC: $14.00 © 1997 American Chemical Society

Acyl Radicals from Thiol Esters
esterification
J . Org. Chem., Vol. 62, No. 17, 1997 5983
Ta ble 1. Cycliza tion of Dia zon iu m Sa lts
deprotection
diazotization
cyclization
reagent
cyclization
entry
product (% yield)
product (% yield)
product (% yield)
product (% yield)
1
2
3
4
5
6
7
8
9
11 (82)
12 (80)
13 (85)
14 (80)
15 (80)
16 (77)
17 (81)
11b
18 (95)
19 (95)
20 (95)
21 (94)
22 (96)
23 (96)
24 (93)
18b
25 (90)
26 (91)
27 (90)
28 (86)
29 (88)
30 (90)
31 (90)
25b
NaI
NaI
NaI
NaI
NaI
NaI
NaI
CuCN
NaSPh
32 (81)
34 (85)
35 (50)a + 32 (25)
36 (75) + 37 (10)
38 (trace) + 39 (24) + 40 (37)
41 (88)
42 (70)
54 (36) + 32 (12) + 55 (12)
56 (35)
12c
19c
26c
a
A single isomer, tentatively assigned the E-configuration owing to the absence of an NOE correlation between the methylene and
olefinic hydrogens. As entry 1. c As entry 2.
b
Ch a r t 1
Sch em e 4
Sch em e 5
Ch a r t 2
Sch em e 3
and isolation of the amines as their hydrochloride salts
(18-24) in close to quantitative yield (Table 1). Finally,
ethanolic solutions of these amine hydrochloride salts
were exposed to tetrafluoroboric acid and isoamyl nitrite,
permitting isolation of the desired diazonium ions as their
tetrafluoroborate salts (25-31) in excellent yield (Table
1).
Dropwise addition of a solution of sodium iodide in
acetone to diazonium salt 25 stirred in thoroughly
degassed acetone at room temperature resulted, after 6
h, in the isolation of the methylenechromanone 32 and
the dihydrobenzothiophene 33 (Chart 2) in 81 and 90%
yields, respectively (Table 1, entry 1). These observations
are best rationalized in terms of the general mechanism
of Scheme 5. Electron transfer from I- to the diazonium
salt (43) results in an aryl radical (44) which participates
in an intramolecular SH2 reaction at sulfur so liberating
the acyl radical (45). Cyclization in the exo mode17 gives
the primary radical (46) which is trapped by iodine,
giving the primary product (47). Elimination of HI from
this â-iodo ketone provides the observed R-methylenecy-
cloalkanone (48). The 1H NMR spectrum of the crude
reaction mixture is consistent with the formation of the
R-(iodomethyl)cycloalkanone (47) as the primary reaction
product, with elimination occurring on attempted chro-
matography over silica gel.
(17) Crich, D.; Chen, C.; Hwang, J .-T.; Yuan, H.; Papadatos, A.;
Walter, R. I. J . Am. Chem. Soc. 1994, 116, 8937-8951.

5984 J . Org. Chem., Vol. 62, No. 17, 1997
Crich and Hao
Sch em e 6
Further examples illustrating the effectiveness of this
chemistry with the 5- and 6-exo mode cyclizations of aryl-
and alkyl-derived acyl radicals are presented in Table 1.
In each case 33 is formed as byproduct, as evident from
the NMR spectra of the crude reaction mixtures. The
overall transformation, with the formation of exometh-
ylene cycloalkanones, is somewhat analogous to that
obtained earlier with acyl tellurides.17 However, the new
chemistry is also applicable to aliphatic carboxylic acids
(Table 1, entry 7) whereas the earlier method was only
suited to aryl and R,â-unsaturated acid derivatives.
Moreover, the stoichiometric use of organotellurium
derivatives of unknown toxicity is avoided.
preferable in view of the dilution and the consequent
improbability of bimolecular radical-radical reactions,
reaction with iodine occurs to give a periodite which then
furnishes the acyloxyl radical (51). A final point of note
here is the preference of the acyloxyl radical (51) for
cyclization in the 6-exo-trig mode over and above 1,5-
hydrogen atom abstraction from a benzylic-allylic site.22
A noteworthy exception to the smooth 5-exo-trig cy-
clizations reported was provided by the p-nitro-substi-
tuted system 29 (Table 1, entry 5). With this substrate
we were unable to isolate significant quantities of the
anticipated 2-methyleneindanone 38, but obtained in-
stead the naphthol 39 and the iodo lactone 40, and this
latter despite all our attempts to exclude oxygen from
the system. This change in behavior is clearly a function
of the p-nitro group as the congenors 28 and 30 (Table
1, entries 4 and 6) were perfectly well behaved. We are
led to conclude that the p-nitro group reduces the
nucleophilicity of the acyl radical significantly by (i) its
strongly electron withdrawing nature and/or (ii) its ability
to stabilize the acyl radical through resonance forms
delocalizing the single electron. Of the two explanations,
the former is perhaps more likely as benzoyl radicals,
being σ-type radicals with the single electron in the plane
of the aromatic ring, are relatively insensitive to reso-
nance effects.26 This reduced reactivity will retard the
cyclization and so increase the likelihood of trapping by
extraneous oxygen and, hence, iodo lactone formation.
The naphthol 39 is the product of a formal 6-endo mode
cyclization. This may arise through the additional
stabilization provided by the p-nitro group, rendering the
normally irreversible27 5-exo-trig acyl radical cyclization
reversible. Alternatively, it is possible that the p-nitro
group promotes a rapid expansion of a kinetic 5-exo-
cyclized radical, via a cyclopropyloxy radical, as studied
by Beckwith, Dowd, and others.28 Indeed, electron-
withdrawing substituents substantially accelerate the
mechanistically related neophyl rearrangement.29
With diazonium salt 28 an unanticipated byproduct
plagued our early experiments. This compound was
isolated and identified as the known iodo lactone 37. Our
first reaction, naturally, was that this product arose from
a competing, polar iodolactonization of either the thiol
ester itself or of the acid formed by in situ hydrolysis of
the thiol ester by adventitious water. However, control
experiments, in which 2-allylbenzoic acid and the N-t-
Boc-protected thiol ester (14) were exposed to the reaction
conditions, soon revealed that this was not the case. A
further experiment, in which 2-allylbenzoic acid was
irradiated in acetone in the presence of iodine and
iodobenzene diacetate,18 however, did lead to the rapid
formation of the iodo lactone 37 and its isolation in 95%
yield. It seems likely, therefore, that 37 is the product
of cyclization of a carboxyl radical onto the alkene
followed by trapping by iodine. The cyclization of aryl-
oxyl radicals, whose decarboxylation is slow,19,20 onto
suitably disposed alkenes and arenes is a known pro-
cess.21,22 This in turn posed the question “what is the
origin of the carboxyl oxygen ?” We reasoned that it
might reasonably come from adventitious water and
hydrolysis of the thiol ester to the acid, or from imper-
fectly excluded oxygen. Of these, the latter possibility
seemed the more likely. Indeed, when the reaction was
repeated after rigorously degassing of the solvent by a
series of freeze-thaw cycles the yield of iodo lactone 37
was reduced to 10% and that of the desired, cyclized
product rose to the 75% reported in Table 1.23 All
subsequent reactions therefore included a rigorous se-
quence of freeze-thaw cycles. The identification of
molecular oxygen as the culprit demands a mechanism
for the formation of acyloxy radicals from acyl radicals
and oxygen. We presume (Scheme 6) that the acyl
radical (49) is quenched by oxygen, giving an acylperoxyl
radical (50). It would seem reasonable that two of these
species combine to give a diacyl tetraoxide which then
looses oxygen to give two carboxyl radicals (51) and so
the observed cyclization. Such processes have been
discussed in the context of gas and liquid phase autoxi-
dations of aldehydes.22,24,25 Alternatively, and perhaps
As Beckwith and Murphy have demonstrated, the
generation of aryl radicals from diazonium salts is by no
means limited to the use of iodide as an electron source.
We have not conducted an extensive survey at the
present time but have demonstrated that both cyanide
and thiophenate anions may be used to replace iodide
(Table 1, entries 8 and 9, respectively). Although the
yield is at present only moderate, the use of cuprous
cyanide for this purpose is especially interesting in so
(18) Concepcion, J . I.; Francisco, C. G.; Freire, R.; Herandez, R.;
Salazar, J . A.; Sua´rez, E. J . Org. Chem. 1986, 51, 402-404.
(19) Chateauneuf, J .; Lusztyk, J .; Ingold, K. U. J . Am. Chem. Soc.
1988, 110, 2886-2893.
(20) Wang, J .; Tsuchiya, M.; Sakuragi, H.; Tokumaru, K. Tetrahe-
dron Lett. 1994, 35, 6321-6324.
(21) Togo, H.; Muraki, T.; Yokoyama, M. Tetrahedron Lett. 1995,
36, 7089-7092.
(25) McDowell, C. A.; Sifnaides, S. Can. J . Chem. 1963, 41, 300-
307.
(22) Wang, J .; Tsuchiya, M.; Tokumaru, K.; Sakuragi, H. Bull.
Chem. Soc. J pn. 1995, 68, 1213-1219.
(26) Brown, C. E.; Neville, A. G.; Rayner, D. M.; Ingold, K. U.;
Lusztyk, J . Aust. J . Chem. 1995, 48, 363-379.
(27) Chatgilialoglu, C.; Ferreri, C.; Lucarini, M.; Venturini, A.;
Zavitsas, A. A. Chem. Eur. J . 1997, 3, 376-387.
(28) Dowd, P.; Zhang, W. Chem. Rev. 1993, 93, 2091-2115.
(29) Abeywickrema, A. N.; Beckwith, A. L. J .; Gerba, S. J . Org.
Chem. 1987, 52, 4072-4078.
(23) Acetone and benzene dissolve O2 to very similar extents (13.0
and 11.2 mol/L, respectively, at 1 atm and 298 K); therefore this
problem is not a function of the solvent. Solubility Data Series, Vol. 7,
O2 and O3, Pergamon: New York, 1981; p 250.
(24) Calvert, J . G.; Hanst, P. L. Can. J . Chem. 1959, 37, 1671-1679.

Acyl Radicals from Thiol Esters
J . Org. Chem., Vol. 62, No. 17, 1997 5985
Hz, 1H), 7.23 (t, J ) 8.7 Hz, 1H), 7.40 (s, 1H), 7.91 (d, J ) 8.0
Hz, 1H); 13C NMR δ 28.3, 29.2, 30.7, 32.3, 80.2, 121.6, 123.5,
127.6, 128.9, 129.6, 136.5, 153.5, 196.9. Anal. Calcd for C15
H21NO3S: C, 60.99, H, 7.17. Found: C, 61.08, H, 7.20.
far as it permits the formation of an additional C-C
bond. The byproducts 32 and 55, from the reaction of
25 with CuCN, are readily understood in terms of
oxidation of the initial cyclized radical, perhaps by
electron transfer to a further molecule of substrate (25),
and by quenching by hydrogen atom abstraction from the
solvent, DMSO, respectively.
-
2-(2-((ter t-Bu tyloxyca r bon yl)a m in o)p h en yl)eth a n eth i-
ol (1). A solution of 5 (2.94 g, 10 mmol) in Et2O (100 mL)
cooled to -20 °C was treated with LiAlH4 (0.57 g, 15 mmol).
The reaction mixture was stirred at 0 °C for 1.5 h before it
was quenched with dilute aqueous HCl (3 M, 20 mL). The
organic layer was separated, washed with water, NaHCO3, and
brine, and dried. Removal of the solvent followed by column
chromatography on silica gel (eluent: CH2Cl2/hexane, 1:2) gave
1 (2.33 g, 92%) as a white solid: mp 44-45 °C; 1H NMR δ
1.46 (t, J ) 8.1 Hz, 1H), 1.52 (s, 9H), 2.77-2.83 (m, 2H), 2.91
(t, J ) 6.9 Hz, 2H), 6.56 (s, 1H), 7.08 (t, J ) 7.1 Hz, 1H), 7.15
(dd, J ) 7.6, 1.1 Hz, 1H), 7.23 (t, J ) 7.4 Hz, 1H), 7.69 (d, J )
8.3 Hz, 1H); 13C NMR δ 25.0, 28.3, 35.4, 80.4, 123.5, 124.6,
127.3, 129.7, 130.9, 135.9, 153.4. Anal. Calcd for C13H19NO2-
S: C, 61.63, H, 7.56. Found: C, 61.62, H, 7.47.
Exp er im en ta l Section
1
Gen er a l. Unless otherwise stated H and 13C NMR spectra
P r oced u r e A: P r ep a r a tion of Th iol Ester s. A solution
of the appropriate carboxylic acid (1 mmol) in benzene (10 mL)
was treated at room temperature with oxalyl chloride (0.87
mL, 10 mmol) and a small drop of DMF. After 0.5 h, the
solvent and excess reagent were removed and CH2Cl2 (15 mL)
was added. DMAP (159 mg, 1.3 mmol) was then added
followed by thiol 1 (278 mg, 1.1 mmol). The resulting mixture
was stirred at room temperature until the reaction was
complete (TLC control). EtOAc (60 mL) was then added and
the resulting solution washed with water, NaHCO3, and brine
and dried. Removal of solvent followed by column chroma-
tography on silica gel gave the pure thiol ester.
(S)-2-(2-((ter t-Bu t yloxyca r b on yl)a m in o)p h en yl)et h yl
2-(a llyloxy)th ioben zoa te (11) was prepared from 2-(allyl-
oxy)benzoic acid17 according to procedure A: chromatography
eluent, CH2Cl2/hexane, 1/1; white solid; mp 61-62 °C; 1H NMR
δ 1.57 (s, 9H), 2.85-2.91 (m, 2H), 3.03-3.09 (m, 2H), 4.71 (dt,
J ) 5.2, 1.5 Hz, 2H), 5.34 (dd, J ) 10.5, 1.4 Hz, 1H), 5.51 (dd,
J ) 17.3, 1.5 Hz, 1H), 6.09-6.15 (m, 1H), 7.01-7.06 (m, 3H),
7.17 (dd, J ) 7.6, 1.6 Hz, 1H), 7.25 (t, J ) 3.8 Hz, 1H), 7.48
(td, J ) 6.6, 0.7 Hz, 1H),7.91-7.94 (m, 2H), 8.00 (d, J ) 8.1
Hz, 1H); 13C NMR δ 28.3, 29.6, 32.6, 69.8, 79.9, 113.3, 118.2,
120.7, 121.2, 123.2, 126.4, 127.5, 129.0, 129.7, 129.9, 132.4,
134.0, 136.6, 153.7, 157.7, 191.5. Anal. Calcd for C23H27NO4-
S: C, 66.80, H, 6.58. Found: C, 67.03, H, 6.80.
(S)-2-(2-((ter t-Bu t yloxyca r b on yl)a m in o)p h en yl)et h yl
2-(m et h a llyloxy)t h iob en zoa t e (12) was prepared from
2-(methallyloxy)benzoic acid17 according to procedure A: chro-
matography eluent, CH2Cl2/hexane, 2:1; colorless oil; 1H NMR
δ 1.57 (s, 9H), 1.91 (d, J ) 0.4 Hz, 3H), 2.86-2.91 (m, 2H),
3.04-3.09 (m, 2H), 4.59 (s, 2H), 5.05 (t, J ) 1.4 Hz, 1H), 5.19
(q, J ) 0.9 Hz, 1H), 6.98-7.05 (m, 3H), 7.17 (dd, J ) 7.6, 1.6
Hz, 1H), 7.25 (t, J ) 7.4 Hz, 1H), 7.47 (td, J ) 8.4, 1.8 Hz,
1H), 7.90-7.93 (m, 2H), 8.03 (d, J ) 7.4 Hz, 1H); 13C NMR δ
19.6, 28.3, 29.6, 32.5, 72.6, 79.9, 113.1, 113.7, 120.5, 121.2,
123.2, 126.3, 127.5, 129.0, 129.7, 129.8, 133.9, 136.6, 140.0,
153.7, 157.7, 191.6. Anal. Calcd for C24H29NO4S: C, 67.42,
H, 6.84. Found: C, 67.61, H, 7.03.
(S)-2-(2-((ter t-Bu t yloxyca r b on yl)a m in o)p h en yl)et h yl
2-(p r op a r gyloxy)th ioben zoa te (13) was prepared from
2-(propargyloxy)benzoic acid17 according to procedure A: chro-
matography eluent, CH2Cl2; colorless oil (350 mg, 85%); 1H
NMR δ 1.57 (s, 9H), 2.57 (t, J ) 2.3 Hz, 1H), 2.86-2.91 (m,
2H), 3.04-3.10 (m, 2H), 4.85 (d, J ) 2.3 Hz, 2H), 7.01 (t, J )
7.1 Hz, 1H), 7.09 (t, J ) 7.6 Hz, 1H), 7.17 (d, J ) 5.6 Hz, 2H),
7.25 (t, J ) 7.6 Hz, 1H), 7.52 (td, J ) 8.0, 1.6 Hz, 1H), 7.87 (s,
1H), 7.92 (dd, J ) 7.8, 1.6 Hz, 1H), 7.99 (d, J ) 8.2 Hz, 1 H);
13C NMR δ 28.3, 29.7, 32.5, 56.5, 76.4, 77.4, 80.0, 113.6, 121.2,
121.5, 123.3, 126.3, 127.5, 128.9, 129.7, 130.0, 133.8, 153.6,
157.7, 191.6. Anal. Calcd for C23H25NO4S: C, 67.13, H, 6,12.
Found: C, 67.24, H, 5.99.
were recorded as CDCl3 solutions at 300 and 75 MHz,
respectively, with chemical shifts (δ) in ppm downfield from
tetramethylsilane as internal standard. All solvents were
dried and distilled by standard methods. Acetone was distilled
under Ar from 4 Å molecular sieves and then subjected to three
freeze-thaw cycles for use in the radical reactions. Extracts
were dried over Na2SO4, and solvents were removed in vacuo.
Microanalyses were performed by Midwest Microlabs, India-
napolis, IN.
2-(2-((ter t-Bu tyloxycar bon yl)am in o)ph en yl)eth an ol (3).
To a stirred 0 °C solution of 2-(2-aminophenyl)ethanol (2) (1.37
g, 10 mmol) in a mixture of dioxane (10 mL), water (5 mL),
and saturated NaHCO3 (5 mL) was added di-tert-butyl dicar-
bonate (2.40 g, 11 mmol). The reaction mixture was stirred
at room temperature for 4 h before water (20 mL) was added.
The organic layer was separated and the aqueous phase
extracted with EtOAc (2 × 10 mL). The combined extracts
were washed with water and brine and then were dried.
Removal of the solvent gave the crude product as a white solid
which was recrystallized from CH2Cl2/hexane to give 3 as
1
colorless crystals (2.13 g, 90%): mp 128-129 °C; H NMR δ
1.51 (s, 9H), 2.09 (s, 1H), 2.83 (t, J ) 5.7 Hz, 2H), 3.89 (t, J )
5.8 Hz, 2H), 7.05 (td, J ) 7.4, 1.1 Hz, 1H), 7.14 (dd, J ) 7.6,
1.1 Hz, 1H), 7.22 (td, J ) 7.4, 1.7 Hz, 1H), 7.65 (s, 1H), 7.71
(d, J ) 8.1 Hz, 1H); 13C NMR δ 28.3, 34.5, 64.1, 80.0, 122.9,
124.1, 127.2, 130.1, 130.7, 137.0, 153.7. Anal. Calcd for C13
H19NO3: C, 65.80, H, 8.07. Found: C, 66.16, H, 8.14.
-
2-(Me syloxy)-1-(2-((t er t -b u t yloxyca r b on yl)a m in o)-
p h en yl)eth a n e (4). To a stirred mixture of 3 (0.711 g, 3
mmol) and Et3N (1.2 mL, 8.6 mmol) in THF (12 mL) cooled to
-30 °C was added dropwise a solution of mesyl chloride (0.46
mL, 6 mmol) in THF (6 mL) over 20 min. After a further 20
min stirring, aqueous NH4Cl was added to render the solution
acidic. The organic layer was separated and the aqueous layer
extracted with EtOAc (3 × 10 mL). The combined extracts
were washed with water and brine and then dried, and
concentrated to dryness. The residue was crystallized from
CH2Cl2, giving 4 as white needles (0.93 g, 99%): mp 104 °C;
1H NMR δ 1.51 (s, 9H), 2.83 (s, 3H), 3.04 (t, J ) 6.6 Hz, 2H),
4.42 (t, J ) 6.6 Hz, 2H), 6.51 (s, 1H), 7.13 (t, J ) 7.4 Hz, 1H),
7.18-7.26 (m, 2H), 7.62 (d, J ) 7.9Hz, 1H); 13C NMR δ 28.2,
31.3, 37.1, 69.6, 80.6, 124.2, 125.1, 128.0, 128.5, 130.2, 136.1,
153.6. Anal. Calcd for C14H21NO5S: C, 53.32, H, 6.71.
Found: C, 53.26, H, 6.70.
(S)-2-(2-((ter t-Bu t yloxyca r b on yl)a m in o)p h en yl)et h yl
Th ioa ceta te (5). To a stirred solution of cesium thioacetate
(4.66 g, 14.3 mmol) in DMF (70 mL) at room temperature was
added 4 (4.10 g, 13 mmol) in DMF (30 mL). The reaction
mixture was stirred for 14 h at room temperature before water
(200 mL) was added. The mixture was extracted with EtOAc
(3 × 100 mL), and the combined extracts were washed with
water and brine and dried. Removal of the solvent followed
by column chromatography on silica gel (eluent: CH2Cl2/
hexane, 4:3) gave 5 as white crystals (3.69 g, 96%): mp 55-
56 °C; 1H NMR δ 1.55 (s, 9H), 2.39 (s, 3H), 2.76-2.82 (m, 2H),
2.91-2.96 (m, 2H), 7.00 (t, J ) 7.3 Hz, 1H), 7.12 (d, J ) 6.6
(S)-2-(2-((ter t-Bu t yloxyca r b on yl)a m in o)p h en yl)et h yl
2-a llylth ioben zoa te (14) was prepared from 2-allylbenzoic
acid17 according to procedure A: chromatography eluent,
CH2Cl2/hexane, 2:1; colorless oil; 1H NMR δ 1.57 (s, 9H), 2.87-
2.92 (m, 2H) 3.05-3.11 (m, 2H), 3.72 (d, J ) 6.5 Hz, 2H), 5.04

5986 J . Org. Chem., Vol. 62, No. 17, 1997
Crich and Hao
(dd, J ) 2.8, 1.8 Hz, 1H), 5.09 (dd, J ) 3.0, 1.6 Hz, 1H), 5.92-
6.03 (m, 1H), 7.04 (td, J ) 7.4, 1.2 Hz, 1H), 7.19 (dd, J ) 7.6,
1.5 Hz, 1H), 7.27-7.34 (m, 3H), 7.47 (td, J ) 7.4, 1.3 Hz, 1H),
7.71 (s, 1H), 7.81 (dd, J ) 8.3,1.0 Hz, 1H), 8.04 (d, J ) 1.2 Hz,
1H); 13C NMR δ 28.4, 29.7, 32.5, 37.5, 80.2, 116.2, 121.6, 123.5,
126.3, 127.7, 128.7, 129.8, 130.8, 132.1, 136.6, 137.1, 138.7,
153.6, 195.4. Anal. Calcd for C23H27NO3S: C, 69.49, H, 6.85.
Found: C, 69.22, H, 6.81.
procedure B: white solid; mp 137-138 °C; 1H NMR (CD3OD)
δ 3.02-3.08 (m, 3H), 3.23-3.28 (m, 2H), 4.87 (d, J ) 2.4 Hz,
2H), 7.08 (td, J ) 8.0, 0.8 Hz, 1H), 7.25 (d, J ) 8.2 Hz, 1H),
7.40-7.58 (m, 5H), 7.75 (dd, J ) 7.8, 1.7 Hz, 1H); 13C NMR
(CD3OD) δ 30.2, 31.9, 57.5, 77.8, 115.5, 122.6, 124.9, 128.8,
130.5, 130.6, 130.7, 132.7, 135.1, 135.5, 157.3, 193.2. Anal.
Calcd for C18H18ClNO2S: C, 62.15, H, 5.22. Found: C, 61.99,
H, 5.33.
(S)-2-(2-((ter t-Bu t yloxyca r b on yl)a m in o)p h en yl)et h yl
2-a llyl-4-n itr oth ioben zoa te (15) was prepared from 8 ac-
cording to procedure A: chromatography eluent, CH2Cl2;
(S)-2-(2-Am in op h en yl)eth yl 2-a llylth ioben zoa te HCl
sa lt (21) was prepared from 14 according to procedure B:
colorless oil; 1H NMR (CD3OD) δ 3.11-3.16 (m, 2H), 3.28-
3.33 (m, 2H), 3.58 (d, J ) 5.8 Hz, 2H), 5.00-5.06 (m, 2H),
5.90-6.03 (m, 1H), 7.35-7.61 (m, 7H), 7.77 (d, J ) 8.0, 1H);
13C NMR (CD3OD) δ 29.9, 31.6, 38.2, 116.1, 124.5, 127.3, 129.3,
129.4, 130.1, 131.9, 132.4, 133.0, 134.7, 138.0, 138.5, 139.4,
195.9; HRMS calcd 297.1187, found 297.1187.
1
yellow crystals; mp 64-65 °C; H NMR δ 1.54 (s, 9H), 2.89-
2.94 (m, 2H), 3.13-3.19 (m, 2H), 3.70 (d, J ) 6.6 Hz, 2H),
5.08-5.18 (m, 2H), 5.86-5.96 (m, 1H), 7.04 (td, J ) 7.4, 1.2
Hz, 1H), 7.18 (dd, J ) 7.6, 1.6 Hz, 1H), 7.26 (td, J ) 5.9, 1.6
Hz, 1H), 7.39 (s, 1H), 7.86 (d, J ) 8.4 Hz, 1H), 7.92 (d, J ) 8.0
Hz, 1H), 8.12-8.15 (m, 2H); 13C NMR δ 28.6, 30.2, 32.4, 37.3,
80.5, 118.1, 121.6, 122.3, 124.0, 125.7, 129.0, 130.0, 135.0,
(S)-2-(2-Am in oph en yl)eth yl 2-allyl-4-n itr oth ioben zoate
HCl sa lt (22) was prepared from 15 according to procedure
1
136.7, 140.8, 142.8, 149.5, 153.8, 194.7. Anal. Calcd for C23
H26N2O5S: C, 62.43, H, 5.92. Found: C, 62.24, H, 5.82.
-
B: white solid; mp 153-154 °C; H NMR (CD3OD) δ 2.94 (s,
2H), 3.15-3.20 (m, 2H), 3.39-3.44 (m, 2H), 3.68 (d, J ) 6.5
Hz, 2H), 5.11 (s, 1H), 5.15 (dd, J ) 8.0, 1.6 Hz, 1H), 5.96-
6.05 (m, 1H), 7.41-7.63 (m, 4H), 7.97 (d, J ) 8.2 Hz, 1H), 8.22
(dd, J ) 9.6, 2.4 Hz, 1H); 13C NMR (CD3OD) δ 30.1, 31.2, 37.7,
117.6, 122.3, 124.5, 126.2, 129.5, 130.2, 130.3, 132.5, 134.5,
136.6, 141.5, 143.9, 150.7, 194.9. Anal. Calcd for C18H19ClN2-
O3S: C, 57.06, H, 5.05. Found:C, 56.53, H, 4.85.
(S)-2-(2-((ter t-Bu t yloxyca r b on yl)a m in o)p h en yl)et h yl
2-a llyl-5-m eth oxyth ioben zoa te (16) was prepared from
2-allyl-5-methoxybenzoic acid according to the procedure A:
chromatography eluent, CH2Cl2/hexane, 5:1; colorless crystals;
mp 50-52 °C; 1H NMR δ 1.55 (s, 9H), 2.85-2.90 (m, 2H), 3.04-
3.10 (m, 2H), 3.60 (d, J ) 6.5 Hz, 2H), 3.84 (s, 3H), 4.99 (dd,
J ) 6.2, 1.8 Hz, 1H), 5.04 (s, 1H), 5.84-5.96 (m, 1H), 6.97-
7.05 (m, 2H), 7,16-7.31 (m, 4H), 7.61 (s, 1H), 7.98 (d, J ) 8.2
Hz, 1H); 13C NMR δ 2.84, 29.7, 32.5, 36.7, 55.4, 80.1, 114.1,
115.8, 117.5, 121.7, 123.6, 127.7, 129.0, 129.8, 130.4, 132.0,
(S)-2-(2-Am in op h en yl)eth yl 2-a llyl-5-m eth oxyth ioben -
zoa te HCl sa lt (23) was prepared from 16 according to
procedure B: white solid; mp 124-125 °C; 1H NMR (CD3OD)
δ 3.06-3.11 (m, 2H), 3.30-3.35 (m, 2H), 3.44 (d, J ) 6.4 Hz,
2H), 3.80 (s, 3H), 4.93 (dd, J ) 8.5, 1.5 Hz, 1H), 4.98 (s, 1H),
5.82-5.95 (m, 1H), 7.04 (dd, J ) 8.5, 2.6 Hz, 1H), 7.19-7.22
(m, 2H), 7.37-7.48 (m, 3H), 7.55 (d, J ) 8.1 Hz, 1H); 13C NMR
(CD3OD) δ 29.9, 31.5, 37.3, 55.8, 114.7, 115.7, 118.2, 124.6,
129.4, 130.2, 130.4, 131.1, 132.5, 133.1, 134.9, 138.4, 139.3,
159.2, 195.7. Anal. Calcd for C19H22ClNO2S: C, 62.71, H,
6.09. Found: C, 62.79, H, 6.14.
136.7, 137.1, 138.0, 153.7, 157.8, 195.2. Anal. Calcd for C24
H29NO4S: C, 67.42, H, 6.84. Found: C, 67.34, H, 6.78.
-
(S)-2-(2-((ter t-Bu tyloxycar bon yl)am in o)ph en yl)eth yl 3,3-
bis(eth oxyca r bon yl)-5-h exen eth ioa te (17) was prepared
from 10 according to procedure A: chromatography eluent,
CH2Cl2; colorless oil; 1H NMR δ 1.25 (t, J ) 7.1 Hz, 6H), 1.54
(s, 9H), 2.74-2.82 (m, 4H), 2.93-2.98 (m, 2H), 3.26 (s, 2H),
4.20 (q, J ) 7.1 Hz, 4H), 5.11 (s, 1H), 5.15 (s, 1H), 5.60-5.76
(m, 1H), 7.01 (t, J ) 7.4 Hz, 1H), 7.07 (s, 1H), 7.12 (d, J ) 6.9
(S)-2-(2-Am in op h en yl)eth yl 3,3-bis(eth oxyca r bon yl)-5-
h exen eth ioa te HCl sa lt (24) was prepared from 17 according
Hz, 1H), 7.23 (t, J ) 7.5 Hz, 1H), 7.85 (d, J ) 8.1 Hz, 1H); 13
C
1
to procedure B: white solid; H NMR (CD3OD) δ 1.23 (t, J )
NMR δ 13.9, 28.3, 28.9, 32.1, 37.1, 45.5, 52.1, 55.7, 61.7, 80.3,
120.0, 122.1, 123.8, 127.6, 128.9, 129.6, 132.0, 136.2, 153.6,
169.5, 196.9. Anal. Calcd for C25H35NO7S: C, 60.83, H, 7.15.
Found: C, 60.58, H, 6.99.
6.9 Hz, 6H), 2.68 (d, J ) 7.3 Hz, 2H), 3.14-3.32 (m, 6H), 4.19
(q, J ) 7.0 Hz, 4H), 5.06 (s, 1H), 5.10 (s, 1H), 5.53-5.64 (m,
1H), 7.33-7.38 (m, 3H), 7.62 (s, 1H), 10.44 (s, 2H); 13C NMR
(CD3OD) δ 14.5, 29.7, 31.9, 38.6, 46.9, 57.3, 63.1, 120.7, 123.7,
129.1, 129.4, 129.7, 132.5, 133.5, 133.6, 171.2, 198.3. Anal.
Calcd for C20H28ClNO5S: C, 55.87, H, 6.56. Found: C, 56.07,
H, 6.47.
P r oced u r e B: Rem ova l of th e Boc Gr ou p . The ap-
propriate Boc-protected amines (1 mmol) were treated at room
temperature with a 3 M HCl/EtOAc solution (5 mL). After
the reaction was complete the solvent was removed and the
residue was added into dry ether. The ether was then
decanted and the residue further washed with ether several
times. The resulting solid can be used directly for the next
step.
(S)-2-(2-Am in op h en yl)eth yl 2-(a llyloxy)th ioben zoa te
HCl sa lt (18) was prepared from 11 according to procedure
B: white solid; mp 131-132 °C; 1H NMR (CD3OD) δ 2.99-
3.23 (m, 2H), 3.20-3.26 (m, 2H), 4.68 (dt, J ) 5.1, 1.6 Hz, 2H),
5.26 (dt, J ) 9.1, 1.6 Hz, 1H), 5.46 (dt, J ) 17.3, 1.7 Hz, 1H),
6.05-6.14 (m, 1H), 7.04 (td, J ) 7.3, 1.0 Hz, 1H), 7.12 (d, J )
8.4 Hz, 1H), 7.34-7.40 (m, 3H), 7.47-7.51 (m, 2H), 7.74 (dd,
J ) 7.8, 1.8 Hz, 1H); 13C NMR (CD3OD) δ 29.8, 31.7, 70.6,
114.7, 117.9, 121.5, 124.3, 127.3, 129.3, 130.0, 130.5, 132.3,
134.0, 134.8, 135.0, 158.3, 191.3. Anal. Calcd for C18H20Cl-
NO2S: C, 61.79, H, 5.76. Found: C, 62.03, H, 5.76.
(S)-2-(2-Am in op h en yl)eth yl 2-(m eth a llyloxy)th ioben -
zoa te HCl sa lt (19) was prepared from 12 according to
procedure B: white solid; mp 126.5-127 °C; 1H NMR (CD3OD)
δ 1.89 (s, 3H), 3.02-3.08 (m, 2H), 3.23-3.28 (m, 2H), 4.60 (s,
2H), 5.00 (s, 1H), 5.15 (s, 1H), 7.02 (t, J ) 7.6 Hz, 1H), 7.12 (d,
J ) 8.4 Hz, 1H), 7.40-7.54 (m, 5H), 7.75 (dd, J ) 7.8, 1.7 Hz,
1H); 13C NMR (CD3OD) δ 19.9, 30.2, 31.9, 73.6, 114.0, 121.7,
125.0, 128.1, 129.6, 130.5, 130.5, 130.6, 130.7, 132.6, 135.3,
135.5, 142.0, 158.6, 193.1. Anal. Calcd for C19H22ClNO2S: C,
62.71, H, 6.09. Found: C, 63.02, H, 6.12.
P r oced u r e C: P r ep a r a tion of Dia zon iu m Sa lts.
A
solution of the appropriate amine hydrochloride (0.1 mmol)
and 48% HBF4 (54 mg, 0.3 mmol) in EtOH (1 mL) at 0 °C was
treated with isoamyl nitrite (20 mg, 0.17mmol). After 30 min,
ether (5 mL) was added to the solution and stirring continued
for another 30 min. A white solid was obtained by filtration
and washed with cold water and ether several times. The solid
was recrystallized from acetone/ether and isolated in the form
of white or yellow crystals. No characterization, other than
1H NMR spectroscopy, was attempted on these compounds
which were used directly in the next step.
2-{2-[[2-(Allyloxy)ben zoyl]th io]eth yl}ben zen ed ia zon i-
u m tetr a flu or obor a te (25) was prepared from 18 according
1
to procedure C: yellow solid; H NMR (CD3COCD3) δ 3.49-
3.63 (m, 2H), 3.57-3.63 (m, 2H), 4.77 (dt, J ) 5.1, 1.5 Hz, 2H),
5.30 (dq, J ) 10.6, 1.5 Hz, 1H), 5.52 (dq, J ) 17.2, 1.7 Hz,
1H), 6.09-6.18 (m, 1H), 7.08 (td, J ) 7.1, 1.0 Hz, 1H), 7.22 (d,
J ) 8.4 Hz, 1H), 7.55-7.61 (m, 1H), 7.77 (dd, J ) 15.5, 1.8
Hz, 1H), 7.98 (td, J ) 7.8, 1.2 Hz, 1H), 8.12 (d, J ) 8.0 Hz,
1H), 8.35 (td, J ) 7.8, 1.3 Hz, 1H), 8.86 (dd, J ) 8.4, 1.2 Hz,
1H).
2-{2-[[2-(Meth a llyloxy)ben zoyl]th io]eth yl}ben zen ed ia -
zon iu m tetr a flu or obor a te (26) was prepared from 19 ac-
1
cording to procedure C: white solid; H NMR (CD3COCD3) δ
1.88 (s, 3H), 3.47-3.53 (m, 2H), 3.55-3.63 (m, 2H), 4.67 (s,
2H), 5.02 (s, 1H), 5.19 (s, 1H), 7.10 (td, J ) 7.7, 1.0 Hz, 1H),
7.23 (d, J ) 4.9 Hz, 1H), 7.57 (td, J ) 7.3, 1.8 Hz, 1H), 7.77
(dd, J ) 7.8, 1.8 Hz, 1H), 7.98 (td, J ) 8.1, 1.1 Hz, 1H), 8.12
(S)-2-(2-Am in op h en yl)eth yl 2-(p r op a r gyloxy)th ioben -
zoa t e HCl sa lt (20) was prepared from 13 according to

Acyl Radicals from Thiol Esters
J . Org. Chem., Vol. 62, No. 17, 1997 5987
(d, J ) 7.9 Hz, 1H), 8.36 (td, J ) 7.8, 1.3 Hz, 1H), 8.86 (dd, J
) 8.4, 1.1 Hz, 1H).
3-(Iod om eth yl)-1-isoch r om a n on e (37):30 1H NMR δ 3.13
(dd, J ) 16.1, 10.4 Hz, 1H), 3.23 (dd, J ) 16.2, 3.7 Hz, 1H),
3.42 (dd, J ) 10.5, 7.2 Hz, 1H), 3.52 (dd, J ) 10.5, 4.6 Hz,
1H), 4.52-4.62 (m, 1H), 7.28 (d, J ) 7.6Hz, 1H), 7.42(t, J )
7.7 Hz, 1H), 7.57 (t, J ) 7.7Hz, 1H), 8.10 (d, J ) 7.7Hz, 1H).
2-{2-[[2-(P r op a r gyloxy)b en zoyl]t h io]et h yl}b en zen e-
d ia zon iu m tetr a flu or obor a te (27) was prepared from 20
according to procedure C: white solid; 1H NMR (CD3COCD3)
δ 3.21 (t, J ) 2.4 Hz, 1H), 3.47-3.53 (m, 2H), 3.58-3.64 (m,
2H), 4.98 (d, J ) 2.4 Hz, 2H), 7.14 (td, J ) 6.9, 0.8 Hz, 1H),
7.33 (d, J ) 8.4 Hz, 1H), 7.63 (td, J ) 8.7, 1.7 Hz, 1H), 7.77
(dd, J ) 7.8, 1.8 Hz, 1H), 7.99 (t, J ) 8.4 Hz, 1H), 8.14 (d, J )
7.5 Hz, 1H), 8.37 (td, J ) 7.8, 1.1 Hz, 1H), 8.87 (d, J ) 8.4 Hz,
1H).
2-[2-[(2-Allylben zoyl)th io]eth yl]ben zen edia zon iu m tet-
r a flu or obor a te (28) was prepared from 21 according to
procedure C: white solid; 1H NMR (CD3COCD3) δ 3.54-3.59
(m, 4H), 3.60-3.68 (m, 2H), 5.00-5.06 (m, 2H), 5.89-6.00 (m,
1H), 7.38 (td, J ) 7.6, 1.3 Hz, 1H), 7.56 (td, J ) 7.5, 1.9 Hz,
1H), 7.79 (dd, J ) 8.7, 1.5 Hz, 1H), 8.00 (td, J ) 8.5, 1.2 Hz,
1H), 8.14 (dd, J ) 7.9, 0.7 Hz, 1H), 8.37 (td, J ) 7.7, 1.3 Hz,
1H), 8.86 (dd, J ) 8.4, 1.2 Hz, 1H).
2-[2-[(2-Allyl-4-n itr oben zoyl)th io]eth yl]ben zen ed ia zo-
n iu m tetr a flu or obor a te (29) was prepared from 22 accord-
ing to procedure C: white solid; 1H NMR (CD3COCD3) δ 3.45-
3.57 (m, 4H), 3.62 (d, J ) 6.4 Hz, 2H), 5.03-5.19 (m, 2H),
5.89-5.99 (m, 1H), 7.85 (t, J ) 7.5 Hz, 1H), 7.95 (dd, J ) 9.2,
3.0 Hz, 1H), 8.01 (d, J ) 7.9 Hz, 1H), 8.15-8.27 (m, 3H), 8.65
(d, J ) 8.4 Hz, 1H).
6-Nit r o-1-n a p h t h ol (39): yellow solid; mp 165-167 °C,
1
lit.31
mp 181-182 °C; H NMR δ 5.51 (s, 1H), 7.01 (dd, J )
7.5, 0.9 Hz, 1H), 7.47 (t, J ) 7.6 Hz, 1H), 7.63 (d, J ) 8.3 Hz,
1H), 8.22 (dd, J ) 9.2, 2.2 Hz, 1H), 8.35 (d, J ) 9.2 Hz, 1H),
8.76 (d, J ) 2.2 Hz, 1H).
3-(Iodom eth yl)-6-n itr oisoch r om an on e (40): yellow solid;
1
mp 120-122 °C; H NMR δ 3.25 (dd, J ) 16.5, 10.8 Hz, 1H),
3.38 (dd, J ) 16.5, 3.5 Hz, 1H), 3.45 (dd, J ) 10.7, 7.1 Hz,
1H), 3.55 (dd, J ) 10.7, 4.5 Hz, 1H), 4.57-4.65 (m, 1H), 8.18
(s, 1H), 8.26 (d, J ) 8.5 Hz, 1H), 8.30 (d, J ) 8.5 Hz, 1H); 13
C
NMR δ 4.8, 33.4, 123.1, 129.7, 132.2, 139.7, 151.0, 162.6;
HRMS calcd 332.9457, found 332.9497.
2-Meth ylen e-6-m eth oxyin d a n on e (41): pale yellow oil;
1H NMR δ 3.68 (s, 2H), 3.85 (s, 3H), 5.62 (dt, J ) 1.7, 0.9 Hz,
1H), 6.35 (dt, J ) 3.5, 0.8 Hz, 1H), 7.20 (dd, J ) 8.4, 2.6 Hz,
1H), 7.30 (d, J ) 2.5 Hz, 1H), 7.38 (d, J ) 8.4 Hz, 1H); 13C
NMR δ 31.0, 55.5, 105.7, 119.1, 124.2, 127.0, 139.4, 142.9,
144.0, 159.4, 193.3. Anal. Calcd for C11H10O2: C, 75.50, H,
5.76. Found: C, 75.60, H, 6.01.
4,4-B is (e t h o x y c a r b o n y l)-2-m e t h y le n e c y c lo p e n t a -
1
n on e (42): colorless oil; H NMR δ 1.27 (t, J ) 7.1 Hz, 6H),
2-[2-[(2-Allyl-5-m et h oxyb en zoyl)t h io]et h yl]b en zen e-
d ia zon iu m tetr a flu or obor a te (30) was prepared from 23
2.91 (s, 2H), 3.24 (t, J ) 2.5 Hz, 2H), 4.22 (q, J ) 7.1 Hz, 1H),
5.42 (q, J ) 1.7 Hz, 1H), 6.07 (q, J )2.0 Hz, 1H); 13C NMR δ
13.9, 36.8, 45.0, 54.0, 62.1, 118.9, 141.4, 170.5, 201.4; HRMS
calcd 240.0998, found 240.0998.
1
according to procedure C: white solid; H NMR (CD3COCD3)
δ 3.43-3.46 (m, 6H), 3.82 (s, 3H), 4.90-4.98 (m, 2H), 5.81-
5.95 (m, 1H), 7.08 (dd, J ) 8.5, 2.7 Hz, 1H), 7.22-7.26 (m,
2H), 7.86 (t, J ) 8.1 Hz, 1H), 7.99 (d, J ) 7.9 Hz, 1H), 8.23 (t,
J ) 7.8 Hz, 1H), 8.63 (d, J ) 8.3 Hz, 1H).
2-{2-[[3,3-Bis(eth oxyca r bon yl)-5-h exen oyl]th io]eth yl}-
ben zen ed ia zon iu m tetr a flu or obor a te (31) was prepared
from 24 according to procedure C: yellow oil; 1H NMR
(CD3COCD3) δ 1.23 (t, J ) 7.1 Hz, 6H), 2.67 (d, J ) 7.5 Hz,
2H), 3.21 (s, 2H), 3.39-3.44 (m, 2H), 3.49-3.54 (m, 2H), 4.16
(q, J ) 7.1 Hz, 4H), 5.10 (s, 1H), 5.15 (d, J ) 4.3 Hz, 1H),
5.63-5.74 (m, 1H), 7.97 (t, J ) 8.5 Hz, 1H), 8.06 (d, J ) 7.4
Hz, 1H), 8.33 (td, J ) 7.8, 1.2 Hz, 1H), 8.83 (dd, J ) 8.4, 1.1
Hz, 1H).
P r oced u r e D: Rea ction of 25-31 w ith Na I. NaI (27 mg,
0.18 mmol) in redistilled, degassed acetone (1 mL) was added
dropwise under Ar into a solution of the diazonium salt (60
mg, 0.15 mmol) in redistilled, degassed acetone (50 mL) at
room temperature. After the addition, the reaction mixture
was stirred for 6 h at room temperature. Removal of the
volatiles and preparative TLC or column chromatography on
silica gel enabled isolation of the various products as indicated
in Table 1.
Cycliza tion of 2-Allylben zoic Acid w ith Iod osoben -
zen e Dia cet a t e: 3-(Iod om et h yl)isoch r om a n on e (40).
Iodosobenzene diacetate (71 mg, 0.22 mmol) and iodine (71
mg, 0.3 mmol) were added to a solution of 2-allylbenzoic acid
(33 mg, 0.2 mmol) in acetone (5 mL) and the mixture irradiated
through Pyrex in a Rayonet photoreactor (254 nm) with
stirring for 1 h at room temperature. Removal of the solvent
followed by chromatography on a silica gel gave 40 (55 mg,
95%) identical with the sample isolated above.
Rea ction of 25 w ith Cu CN: 3-(Cya n om eth yl)ch r o-
m a n on e (54) a n d 3-Meth ylch r om a n on e (55). A solution
of CuCN (11 mg, 0.12 mmol) in DMSO (1 mL) was added
dropwise to a solution of 25 (40 mg, 0.1 mmol) in DMSO (20
mL). After addition was complete the reaction mixture was
stirred for 12 h before brine (50 mL) was added and the
mixture was extracted with EtOAc (3 × 20 mL). The combined
extracts were washed with water and brine and dried. After
removal of the solvent, purification by column chromatography
on silica gel (eluent: first CH2Cl2/hexane, 1:1; then CH2Cl2/
EtOAc, 9:1) gave 54 as a colorless oil (6.7 mg, 36%), 55 (2 mg,
12%), and 32 (2 mg, 12%). 54: 1H NMR δ 2.60 (dd, J ) 17.3,
9.1 Hz, 1H), 3.00 (dd, J ) 17.3, 4.6 Hz, 1H), 3.14-3.23 (m,
1H), 4.35 (t, J ) 11.7 Hz, 1H), 4.75 (dd, J ) 11.4, 5.2 Hz, 1H),
7.02 (d, J ) 8.5 Hz, 1H), 7.07 (t, J ) 8.0 Hz, 1H), 7.53 (td, J
) 7.2, 1.7 Hz, 1H), 7.90 (dd, J ) 7.9, 1.8 Hz, 1H); 13C NMR δ
14.1, 42.0, 69.4, 117.1, 117.9, 119.8, 122.0, 127.4, 136.6, 161.6,
190.0; HRMS calcd 187.0633, found 187.0633. 55:2 1H NMR
δ 1.23 (d, J ) 7.0 Hz, 3H), 2.83-2.91 (m, 1H), 4.16 (t, J )
11.2 Hz, 1H), 4.51 (dd, J ) 11.3, 5.1 Hz, 1H), 6.96 (d, J ) 8.8
Hz, 1H), 7.02 (t, J )7.0 Hz, 1H), 7.47 (td, J ) 9.0, 1.8 Hz, 1H),
7.90 (dd, J ) 7.8, 1.7 Hz, 1H).
3-Meth ylen ech r om a n on e (32):17 1H NMR δ 5.01 (dd, J
) 1.5, 1.3 Hz, 1H), 5.58 (dt, J ) 1.5, 1.1 Hz, 1H), 6.32 (dt, J )
1.3, 1.1 Hz, 1H), 6.98 (dd, J ) 8.4, 0.9 Hz, 1H), 7.06 (ddd, J )
8.0, 7.8, 0.9 Hz, 1H), 7.49 (ddd, J ) 8.4, 7.8, 1.8 Hz, 1H), 7.99
(dd, J ) 8.0, 1.8 Hz, 1H).
2,3-Dih yd r oben zoth iop h en e (33):2 1H NMR δ 3.27-3.38
(m, 4H), 7.00 (t, J ) 7.3 Hz, 1H), 7.11 (t, J ) 7.3 Hz, 1H), 7.20
(t, J ) 8.2 Hz, 1H).
3-(Iod om eth yl)-3-m eth ylch r om a n on e (34): colorless oil;
1H NMR δ 1.27 (s, 3H), 3.27 (d, J ) 10.4 Hz, 1H), 3.55 (d, J )
10.4 Hz, 1H), 4.18 (d, J ) 11.7 Hz, 1H), 4.40 (d, J ) 11.7 Hz,
1H), 6.97 (dd, J ) 7.4, 0.7 Hz, 1H), 7.04 (td, J ) 8.0, 1.0 Hz,
1H), 7.50 (td, J ) 7.6, 1.8 Hz, 1H), 7.90 (dq, J ) 7.9, 0.3 Hz,
1H); 13C NMR δ 10.0, 19.1, 44.6, 75.5, 117.8, 119.2, 127.8,
136.1, 161.0, 192.4; HRMS calcd 301.9763, found 301.9803.
3-(Iod om eth ylen e)ch r om a n on e (35): colorless oil; 1H
NMR δ 5.07 (d, J ) 1.8 Hz, 2H), 7.00 (d, J ) 8.4 Hz, 1H), 7.07
(t, J ) 7.9 Hz, 1H), 7.51 (td, J ) 7.2, 1.2 Hz, 1H), 7.98 (dd, J
) 7.9, 1.5 Hz, 1H), 8.05 (t, J ) 1.7 Hz, 1H); 13C NMR δ 73.0,
97.0, 118.1, 120.4, 122.2, 128.0, 136.4, 141.6, 161.6, 178.1;
HRMS calcd 285.9450, found 285.9490.
Rea ction of 26 w ith P h SNa : 3-Meth yl-3-((p h en ylth io)-
m eth yl)ch r om a n on e (56). A solution of PhSNa (0.184
mmol) in DMSO (0.5 mL) was added to a solution of 26 (52
mg, 0.12mmol) in DMSO (15 mL) at room temperature and
the mixture stirred under Ar for 6 h. After extractive workup
the residue was separated by column chromatography on silica
gel (eluent: CH2Cl2/hexane, 2:1), giving 56, a pale yellow oil
(12 mg, 35%), as the only significant cyclized product: 1H NMR
δ 1.27 (s, 3H), 3.20 (d, J ) 13.4 Hz, 1H), 3.31 (d, J ) 13.4 Hz,
1H), 4.18 (d, J ) 11.6 Hz, 1H), 4.49 (d, J ) 11.6 Hz, 1H), 6.95
(dd, J ) 8.3, 0.7 Hz, 1H), 7.03 (td, J ) 7.2, 1.1 Hz, 1H), 7.20
3-Meth ylen ein d a n on e (36):17 1H NMR (CDCl3) δ 3.75 (s,
2H), 5.65 (s, 1H), 6.37 (s, 1H), 7.38 (t, J ) 7.7 Hz, 1H), 7.48 (d,
J ) 5.0 Hz, 1H), 7.60 (t, J ) 5.0 Hz, 1H), 7.85 (d, J ) 7.7 Hz,
1H).
(30) Grunewald, G. L.; Dahanukar, V. H. J . Heterocycl. Chem. 1994,
31, 1609-1618.
(31) Hodgson, H. H.; Turner, H. S. J . Chem. Soc. 1944, 8-10.

5988 J . Org. Chem., Vol. 62, No. 17, 1997
Crich and Hao
(d, J ) 7.2 Hz, 1H), 7.24-7.30 (m, 2H), 7.40 (dd, J ) 8.5, 1.5
Hz, 1H), 7.48 (td, J ) 7.1, 1.2 Hz, 1H), 7.92 (dd, J ) 7.7, 0.7
Hz, 1H); 13C NMR δ 18.0, 38.8, 46.5, 74.0, 118.0, 119.7, 121.9,
126.8, 128.1, 129.2, 130.2, 136.2, 136.8, 161.3, 195.5. Anal.
Calcd for C17H16O2S: C, 71.80, H, 5.67. Found: C, 71.60, H,
5.57.
Su p p or tin g In for m a tion Ava ila ble: Protocols for the
1
synthesis of 7-10, H NMR spectra for diazonium salts 25-
1
31, and H and 13C NMR spectra for 21, 34, 35, 40, 42, and 54
(22 pages). This material is contained in libraries on micro-
fiche, immediately follows this article in the microfilm version
of the journal, and can be ordered from the ACS; see any
current masthead page for ordering information.
Ack n ow led gm en t. We thank the NIH (CA60500)
for support of this work.
J O970500J