Vinyl-λ3-iodanes act as efficient sulfur atom acceptors: Vinylic SN2-based strategy for conversion of tertiary thioamides to amides

Article abstract of DOI:10.1039/b209097j

Exposure of tertiary thioamides to (E)-1-hexenyl(phenyl)-λ³-iodane results in vinylic S_N2 reaction to give the inverted (Z)-S-vinylthioimidonium salts, which under alkaline hydrolysis (Na₂CO₃ or K₂CO<

Full text of DOI:10.1039/b209097j

3
Vinyl-l -iodanes act as efficient sulfur atom acceptors: vinylic S 2-based
N
strategy for conversion of tertiary thioamides to amides
Masahito Ochiai* and Shinji Yamamoto
Faculty of Pharmaceutical Sciences, University of Tokushima, 1-78 Shomachi, Tokushima 770-8505, Japan.
E-mail: mochiai@ph2.tokushima-u.ac.jp; Fax: +81 88 633 9504; Tel: +81 88 633 7281
Received (in Cambridge, UK) 18th September 2002, Accepted 8th October 2002
First published as an Advance Article on the web 24th October 2002
Exposure of tertiary thioamides to (E)-1-hexenyl(phenyl)-
1, a variety of N,N-dimethyl and N-methyl-N-phenyl tertiary
thioamides as well as cyclic N-methylpyrrolidine-2-thione
afford S-vinylthioimidonium salts 2 in high yields.
The imidonium salts 2 are labile and highly susceptible to
hydrolysis with moisture (Scheme 2); exposure of 2a to THF–
3
l -iodane results in vinylic S
Z)-S-vinylthioimidonium salts, which under alkaline hy-
drolysis (Na CO or K CO ) selectively afford amides, while
N
2 reaction to give the inverted
(
2
3
2
3
(
Z)-S-vinyl thioesters are obtained in high yields via the
hydrolysis under acidic conditions (HCl).
2
H O (10:1) at room temperature for 4 h results in the hydrolysis
1
2
to give a mixture of the amide 3a (R = c-C
6
H11, R = Me,
3
(
E)-Alkenyl(phenyl)-l -iodanes 1 undergo vinylic S
N
2 reac-
71%) (probably with liberation of (Z)-1-mercapto-1-hexene)
n
1
tions under mild conditions because of the very high leaving
and (Z)-S-vinyl thiocarboxylate 4a (R = Bu , R = c-C
6 11
H ,
3
1
group ability of phenyl-l -iodanyl groups. The reaction affords
29%). Use of alkali metal carbonates (M CO : M = Na, K, Rb,
2
3
(
Z)-vinylic compounds with exclusive inversion of configura-
Cs) as an additive not only accelerates the hydrolysis but also
increases the selectivity for amide formation (Table 2): thus,
Na CO or K CO in THF gave a high yield of the amide 3a
2 3 2 3
( > 90%) within 20 min at room temperature (Table 2, entries 2
and 3), along with the formation of (Z)-S-vinyl thiocarboxylate
4a in less than 8% yield. Formation of thioamide (14–17%) was
observed when the hydrolysis was carried out in the presence of
2,3
N
tion. Nucleophiles that undergo vinylic S 2 reaction with (E)-
3
2
alkenyl(phenyl)-l -iodanes 1 include halides, dialkyl sulfides
4a
and selenides,3a phosphoroselenoates, dithiocarbamates,
4b
5
and carboxylic acids. Formamides and acetamides with rather
3
low nucleophilicity also act as good nucleophiles toward l -
iodanes 1, and afford (Z)-vinyl formates and (Z)-vinyl acetates,
respectively, in a highly stereoselective manner.6 Use of
thioamides as nucleophiles, however, affords (Z)-enethiols
7
stereoselectively, instead of (Z)-S-vinyl thiocarboxylates: for
instance, reaction of (E)-1-decenyl(phenyl)-l -iodane 1b with
3
thioacetamide in dichloromethane at room temperature results
in formation of (Z)-1-mercaptodec-1-ene in 82% yield with
exclusive inversion of configuration. This reaction involves the
intervention of the highly labile (Z)-S-vinylthioimidonium salt,
produced through nucleophilic attack by the sulfur atom of
3
Scheme 1
thioacetamide on (E)-1-decenyl-l -iodane 1b from the side
4
opposite the hyperleaving group PhI(BF ) stereoselectively.
Table 1 Synthesis of (Z)-S-vinylthioimidonium tetrafluoroborates 2 via
Subsequent hydrolysis of the (Z)-S-vinylthioimidonium salt
affords the retained (Z)-enethiol. The fact that, in the reaction
3
a
vinylic S
N
2 reaction of vinyl-l -iodane 1a with thioamides
3
with thioamides, (E)-alkenyl(phenyl)-l -iodane 1b selectively
Thioamide
Product [yield (%)]b
captures the sulfur atom by forming (Z)-enethiols suggested to
3
us that the l -iodane 1 could function as an agent for the
R1
R2
Entry
T/°C (t/h)
2
conversion of thioamides to amides. We report herein on vinylic
S
N
2-based conversion of thioamides into amides, in which (E)-
1
2
3
4
5
6
7
8
9
a
c-C H
Me
Me
Me
Me
Me
Me
Ph
50 (17)
25 (48)
50 (14)
25 (32)
25 (47)
25 (55)
50 (15)
50 (15)
50 (13)
2a (98)
2b (92)
2c (91)
2d (92)
2e (92)
2f (95)
2g (97)
2h (94)
2i (93)
6
n
11
3
alkenyl(phenyl)-l -iodanes 1 act as efficient sulfur atom
Bu
c-C
Ph
acceptor agents.
H
5 9
Diverse synthetic methods are available for the conversion of
8
6 4
p-MeC H
thioamides into amides. These include oxidative conversion
p-ClC
Bu
6
H
4
using hydrogen peroxide, m-chloroperbenzoic acid, diaryl
telluroxide, manganese dioxide and (diacetoxyiodo)benzene, as
well as hydrolytic conversion catalyzed by soft metal ions such
n
Ph
Ph
2 3
–(CH ) –
as Cu(
I
), Ag( ) and Hg(II). Alkylation of thioamides followed by
I
Reactions were carried out using a thioamide (1.1 equiv.) in dichloro-
alkaline hydrolysis is an effective alternative for conversion into
amides.
b
2
methane under N . Isolated yields.
3
Exposure of tertiary thioamides to (E)-1-hexenyl(phenyl)-l -
iodane 1a, prepared from (E)-1-hexenylboronic acid by the
3
BF -catalyzed reaction with (diacetoxyiodo)benzene via boron-
3
9
N
l -iodane exchange in 82% yield, results in vinylic S 2
reaction to give the inverted (Z)-S-vinylthioimidonium salts 2
stereoselectively in > 90% yields (Scheme 1). For instance,
3
reaction of l -iodane 1a with N,N-dimethylcyclohexanecarbo-
thioamide in dichloromethane at 50 °C for 17 h gave (Z)-S-
vinylthioimidonium tetrafluoroborate 2a (98%) as a colorless
oil.† A small vicinal coupling constant (J = 8.9 Hz) between
1
the vinylic protons in H NMR indicates a cis structure. The
1
reaction is exclusively stereoselective to the limits of H NMR
detection with inversion of olefin geometry. As shown in Table
Scheme 2
2
802
CHEM. COMMUN., 2002, 2802–2803
This journal is © The Royal Society of Chemistry 2002

Table 2 Hydrolysis of (Z)-S-vinylthioimidonium tetrafluoroborates 2 to
amides 3 under basic conditions
decyl sulfide (72%), along with the formation of amide 3a
81%) and thioester 4a (6%). The extent of C–S bond cleavage
7
a
(
decreases when the reaction was carried out under acidic
conditions. Under acidic conditions, protonation to the tetra-
hedral intermediate 5 with formation of the conjugate acids
would play an important role and the (Z)-S-vinyl thiocarbox-
ylate 4 is produced selectively through protonation at the more
basic nitrogen atom. Amide formation via S-protonation of 5
will be a disfavoured process.
In the alkali metal carbonate-accelerated hydrolysis of 2,
changing the metal cation from Li to Na, K, Rb and Cs increases
the selectivity for formation of the amide 3 over the thioester 4
Product [yield (%)]b
Entry
2
Base (equiv.)
t
3
4
(1)c
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2a
2a
2b
2c
2d
2d
2e
2e
2f
Li
5% Na
5% K CO
5% Rb
5% Cs
AgOAc (2)
2
CO
3
20 min
20 min
20 min
20 min
20 min
20 min
20 min
20 min
4 h
70
30
8
8
2
CO
3
3
(1)
(1)
92 (79)
92 (67)
79
2
de
2
CO
3
(1)
(1)
4
d
2
CO
3
c
83
3
87 (58)
89
13
9
5% Na
5% Na
5% Na
2
2
2
CO
CO
CO
3
3
3
(1)
(1)
(
Table 1, entries 1–5). The results probably reflect differences
88
11
—
13
—
9
in ionicity in the metal–oxygen bond, which increase in the
order Li CO < Na CO < K CO < Rb CO < Cs CO .
2 3 2 3 2 3 2 3 2 3
d
(2)
83 (82)
86 (86)
80
1
1
f
10
11
12
13
14
15
16
17
a
AgOAc (1.2)
3 h
3 h
3 h
2 h
d
An increased ionicity will result in a decrease in the rate of N-
protonation of 5 leading to the formation of the thioester 4.
In conclusion, a vinylic S 2-based strategy provides a
N
5% K
AgOAc (1.2)
5% K CO
(2)d
2
CO
3
(2)
f
85
2
3
80
5
2g
2h
2i
5% Na
5% Na
2
CO
CO
3
(1)
(1)
20 min
30 min
30 min
4 h
84
4
method for conversion of thioamides to amides, in which (E)-
3
2
3
83
81
88
13
—
—
alkenyl(phenyl)-l -iodanes serve as efficient sulfur atom accep-
5% K
AgOAc (1.2)
2
CO
3
(2)
tors. The basic hydrolysis of (Z)-S-vinylthioimidonium salts 2
involves selective C–S bond cleavage of charged tetrahedral
intermediates 6, whereas the acidic hydrolysis involves se-
lective C–N bond cleavage of the conjugate acids of 5.
f
2i
Unless otherwise noted, reactions were carried in THF at room
b
1
temperature under nitrogen. Yields were determined by H NMR. Isolated
c
d
yields are shown in parenthesis. In THF–H
2
O (2+1). Thioamides were
obtained in 14–20% yields. e Reaction temperature: 0 °C. In THF–H
f
O
2
(4+1).
Notes and references
Rb
effective alternative and afforded 3a in 87% yield (Table 2,
entry 6). Hydrolysis of the cyclic imidonium salt 2i with K CO
2 3 2 3 2
CO or Cs CO . Use of AgOAc in THF–H O (2+1) is an
†
Typical experimental procedure for synthesis of (Z)-S-vinylthioimidon-
3
ium tetrafluoroborates 2 (Table 1, entry 1): to a stirred solution of l -iodane
2
3
1
a (0.27 mmol) in dichloromethane (5 mL) was added N,N-dimethylcyclo-
gave an 81% yield of N-methyl-2-pyrrolidinone 3i. The alkaline
hexanecarbothioamide (0.29 mmol) at room temperature under nitrogen and
the mixture was warmed at 50 °C for 17 h. After cooling, the mixture was
concentrated in vacuo. Purification of the crude product by repeated
decantation with dichloromrthane–hexane gave (Z)-S-vinylthioimidonium
1
hydrolysis of the imidonium salts 2d–f with aromatic R group
proceeds slowly and takes a longer reaction time than that of
1
2
a–c with aliphatic R groups.
tetrafluoroborate 2a (98%) as a colorless oil: d
H
(300 MHz, CDCl
.93 (t, J 7.1, 3H), 1.2–1.8 (m, 10H), 1.90–2.05 (m, 4H), 2.31 (q, J 6.8, 2H),
.09 (tt, J 11.6 and 3.2, 1H), 3.68 (s, 3H), 3.78 (s, 3H), 6.33 (br d, J 8.9, 1H),
.38 (dt, J 8.9 and 6.8, 1H); nmax(neat)/cm 2931, 2859, 1607, 1453,
150–1000; HRMS (FAB): calc. for C15
3
, J/Hz)
In marked contrast, hydrolysis of the imidonium salts 2 under
0
3
6
1
2
acidic conditions is slow and selectively gives rise to (Z)-S-
vinyl thiocarboxylates 4: thus, treatment of 2a with 10%
aqueous HCl solution at room temperature for 11 h afforded the
thiocarboxylate 4a as a colorless oil in 81% yield, along with the
formation of the amide 3a (14%).10 Under similar conditions,
the imidonium salts 2c, 2g and 2h gave the (Z)-S-vinyl
2
1
+
H
4
28NS [(M 2 BF ) ], m/z
54.1942, found 254.1962.
n
1
1
1 (a) T. Okuyama, T. Takino, T. Sueda and M. Ochiai, J. Am. Chem. Soc.,
1995, 117, 3360; (b) M. Ochiai, in, Chemistry of Hypervalent
Compounds, ed. K. Akiba, Wiley–VCH, New York, 1999, ch. 12.
5 9
thiocarboxylates 4c (R = Bu , R = c-C H ), 4g (R = R =
n
n
1
Bu ) and 4h (R = Bu , R = Ph) in 81, 72 and 83% yields,
respectively. Acidic hydrolysis accompanies the isomerization
of the double bond geometry to a discernible extent by H
2
(a) M. Ochiai, K. Oshima and Y. Masaki, J. Am. Chem. Soc., 1991, 113,
059; (b) T. Okuyama, T. Takino, K. Sato and M. Ochiai, J. Am. Chem.
1
7
NMR: less than 5% for 4c and 4g, and 10% for 4h.
Soc., 1998, 120, 2275; (c) T. Okuyama, T. Takino, K. Sato, K. Oshima,
S. Imamura, H. Yamataka, T. Asano and M. Ochiai, Bull. Chem. Soc.
Jpn., 1998, 71, 243.
Hydrolysis of the imidonium salts 2 under basic conditions
probably involves the tetrahedral uncharged 5 and charged
intermediates 6 (Scheme 3). Decomposition of 6 is a product
determining step and selectively produces the amide 3 through
C–S bond cleavage with liberation of (Z)-enethiol, because of
the greater leavimg ability of a vinylthio group than that of an
amino group. Formation of (Z)-enethiol 7 was confirmed by the
3
3 For reviews of nucleophilic vinylic substitutions of alkenyl(phenyl)-l -
iodanes, see: (a) M. Ochiai, J. Organomet. Chem., 2000, 611, 494; (b)
T. Okuyama, Rev. Heteroat. Chem., 1999, 21, 678; (c) N. Sh Pirkuliev,
V. K. Brel and N. S. Zefirov, Russ. Chem. Rev., 2000, 69, 105; (d) G. F.
Koser, in, The Chemistry of Halides, Pseudo-halides and Azides,
Supplement D2, ed. S. Patai and Z. Rappoport, Wiley, New York, 1995,
ch. 21.
hydrolysis (5% Na
2
CO
3 8
/THF/rt/25 min) of 2j (R = n-C H
17, R1
2
=
c-C
6
H11, R = Me), which afforded a mixture of (Z)-enethiol
4
(a) J. Yan and Z.-C. Chen, Tetrahedron Lett., 1999, 40, 5757; (b) J. Yan
and Z.-C. Chen, Synth. Commun., 1999, 29, 2867.
7
(R = n-C
8
H17, 14%) and its dimer, (Z)-1-decenyl 1-mercapto-
5
6
7
T. Okuyama and M. Ochiai, J. Am. Chem. Soc., 1997, 119, 4785.
M. Ochiai, S. Yamamoto and K. Sato, Chem. Commun., 1999, 1363.
M. Ochiai, S. Yamamoto, T. Suefuji and D.-W. Chen, Org. Lett., 2001,
3
, 2753.
For reviews, see: A. Corsaro and V. Pistara, Tetrahedron, 1998, 54,
5027; W. Walter and J. Voss, in, The Chemistry of Amides, ed. J.
8
9
1
Zabicky, Wiley, London, 1970, ch. 8.
M. Ochiai, M. Toyonari, T. Nagaoka, D.-W. Chen and M. Kida,
Tetrahedron Lett., 1997, 38, 6709.
1
0 For hydrolysis of thioimidate esters, see: (a) R. K. Chaturvedi, A. E.
MacMahon and G. L. Schmir, J. Am. Chem. Soc., 1967, 89, 6984; (b) R.
K. Chaturvedi and G. L. Schmir, J. Am. Chem. Soc., 1969, 91, 737; (c)
R. E. Barnett and W. P. Jencks, J. Am. Chem. Soc., 1969, 91, 2358.
1 (a) M. G. Stanton and M. R. Gagne, J. Am. Chem. Soc., 1997, 119, 5075;
1
(b) C. Lambert and R. Schleyer, Angew. Chem., Int. Ed. Engl., 1994, 33,
Scheme 3
1129.
CHEM. COMMUN., 2002, 2802–2803
2803