Rhodium-catalyzed addition of arylboronic acids to 2-methylene-1,3-dithiane monoxide

Article abstract of DOI:10.1055/s-2007-980373

Treatment of 2-methylene-1,3-dithiane 1-oxide with arylboronic acid under rhodium catalysis in aqueous dioxane at 25°C provided the corresponding adduct, which is a useful 2-aryl-alkanal equivalent. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-980373

1622
LETTER
Rhodium-Catalyzed Addition of Arylboronic Acids to 2-Methylene-1,3-
dithiane Monoxide
A
ddition of Ar
u
ylboronic
A
g
u
thylene-1, 3-d
r
ithiane
Monoxide Yoshida, Hideki Yorimitsu,* Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura, Nishikyo-ku,
Kyoto 615-8510, Japan
Fax +81(75)3832438; E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp; E-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received 23 March 2007
Table 1 Rhodium-Catalyzed Addition of Arylboronic Acids 2 to 2-
Methylene-1,3-dithiane 1-Oxide (1a)a
Abstract: Treatment of 2-methylene-1,3-dithiane 1-oxide with
arylboronic acid under rhodium catalysis in aqueous dioxane at
25 °C provided the corresponding adduct, which is a useful 2-aryl-
alkanal equivalent.
O–
S+
O–
1a
S
Key words: rhodium, arylboronic acid, addition, methylene
dithiane monoxide
cat. [Rh(OH)(cod)]2
S+
R
+
1,4-dioxane, H2O
25 °C, 3 h
S
R
3
B(OH)2
Ketene dithioacetal is useful as a ketene equivalent in
organic synthesis.1 In the course of our studies on the use
of ketene dithioacetal as substrates for metal-catalyzed
organic reactions,2 we examined rhodium-catalyzed
addition reactions to ketene dithioacetals. However, no
reaction took place after several attempts. We turned our
attention to the use of activated ketene dithioacetals. We
now report that 2-methylene-1,3-dithiane 1-oxide (1a) un-
dergoes rhodium-catalyzed addition of arylboronic acids.3
Similar rhodium-catalyzed 1,4-additions to a,b-unsaturat-
ed carbonyl compounds are extensively studied.4 On the
other hand, the reactions of heteroatom-substituted elec-
tron-deficient alkenes are still unexplored.5
2
Entry
R
H
2
3
Yield (%)
1
2
3
4
5
6
7
2a
2b
2c
2d
3a
3b
3c
3d
3e
3f
97
89
p-MeO
p-Me
p-CF3
89
100
90
p-MeOOC
o-MeO
2e
2f
96
o-BocNHb
2g
3g
96c
Treatment of 1a with phenylboronic acid (2a, 1.2 equiv)
in the presence of [Rh(OH)(cod)]2 (5 mol%) in aqueous
dioxane at 25 °C for 3 hours provided the corresponding
adduct 3a in 97% yield (Table 1, entry 1).6 The reaction
was completely stereoselective,7 and none of the trans-
isomer of 3a was detected.8
a Reaction conditions are described in ref. 6.
b Boc = t-BuOC(=O).
c 2 equiv of 2g.
O–
S+
A variety of arylboronic acids participated in the reaction.
Electron-donating as well as electron-withdrawing sub-
stituents had little influence on the efficiency of the reac-
tions (entries 2–5). Arylboronic acids having a substituent
at the ortho position added to 1a under the rhodium catal-
ysis to yield the corresponding adducts in excellent yields
(entries 6 and 7). Alkenylboronic acid 2h was less reac-
tive, and an excess of 1,5-cyclooctadiene and a larger
amount of the rhodium complex were necessary to
achieve satisfactory yield (Scheme 1).
O–
10 mol% [Rh(OH)(cod)]2
S+
1a
S
+
2.0 equiv COD
Ph
S
Ph
1,4-dioxane, H2O
25 °C, 3 h
B(OH)2
2h (1.5 equiv)
3h 70%
Scheme 1
with an excess of 2a (Scheme 2). In contrast to the reac-
tion of 1a, the reaction of 4 provided a mixture of stereo-
isomers.
Acyclic ketene dithioacetal monoxide 4 was the less reac-
tive Michael acceptor to furnish 59 in only 41% yield and
to recover 40% of 4 even at an elevated temperature and
O–
Me
5 mol% [Rh(OH)(cod)]2
Me
O–
S+
S+
2.0 equiv PhB(OH)2
Ph
Me
Me
S
1,4-dioxane, H2O
100 °C, 12 h
S
5
41%
4
(6:4 mixture of diastereomers)
SYNLETT 2007, No. 10, pp 1622–1624
1
8
.0
6
.2
0
0
7
+ 4 (40% recovery)
Advanced online publication: 07.06.2007
DOI: 10.1055/s-2007-980373; Art ID: U02507ST
© Georg Thieme Verlag Stuttgart · New York
Scheme 2

LETTER
Addition of Arylboronic Acids to 2-Methylene-1,3-dithiane Monoxide
1623
The phenylation reaction of 1b required a longer reaction Treatment of 3g with trifluoroacetic anhydride in nitro-
time and two equivalents of phenylboronic acid, yet af- methane provided N-Boc-protected indole 10 in excellent
fording an excellent yield of the corresponding product 6a yield (Scheme 5). The trifluoroacetylation of the
(Scheme 3). The reaction of 1c with a large excess of sulfoxide oxygen followed by the cleavage of the carbon–
phenylboronic acid proceeded to completion within 24 sulfur bond13 would yield the cationic intermediate 12. In-
hours with the aid of 10 mol% of [Rh(OH)(cod)]2. In this tramolecular attack of the Boc-protected amino group led
case, a small amount of a stereoisomer was detected, the to the formation of the dihydroindole 13 with concomitant
configuration of which has not been assigned yet.10 Un- liberation of trifluoroacetate. Elimination of dithiacyclo-
fortunately, gem-diphenyl-substituted 1d resisted the pentane yielded 10.
reaction.
Boc
Boc
5 mol% [Rh(OH)(cod)]2
2.0 equiv PhB(OH)2
NH
O–
O–
2.0 equiv (CF3CO)2O
S+
S+
S
N
Ph
Ph
MeNO2, 0 °C, 30 min
S+
O–
1,4-dioxane, H2O
25 °C, 15 h
S
S
3g
10 92%
Ph
Ph
6a 90%
1b
10 mol% [Rh(OH)(cod)]2
6.0 equiv PhB(OH)2
O–
O–
Boc
NH
Boc
S+
S+
Boc
N
NH
S+
S
+
S
1,4-dioxane, H2O
25 °C, 24 h
S
S
+
S
Me
Me
6b 70%
diastereomer ratio
major/minor > 10:1
1c
S
S
CF3
CF3COO–
O
CF3
O
CF3COO–
O–
O–
5 mol% [Rh(OH)(cod)]2
2.0 equiv PhB(OH)2
CF3COO–
13
S+
S+
O
O
11
12
Ph
Ph
Ph
1,4-dioxane, H2O
25 °C, 24 h
S
S
Scheme 5
Ph
Ph
6c 0%
1d
Scheme 3
In summary, we have found rhodium-catalyzed addition
of arylboronic acids to ketene equivalents 1. The products
are 2-arylalkanal equivalents, which can be subjected to a
variety of organic transformations.
The products 3 and 6 are 2-arylalkanal equivalents. We
examined the utility of the products (Scheme 4). All the
attempts to convert 3a into phenylacetaldehyde resulted in
the formation of complex mixtures or no conversion. In-
stead, treatment of 3a with ethylene glycol in the presence
of sulfuric acid in hot toluene afforded 2-benzyl-1,3-diox-
olane (7) in 84% yield.11 Deprotonation of 3a with lithium
diisopropylamide followed by addition of iodomethane
provided a benzyl methyl ketone equivalent 8 in good
yield.12 Interestingly, under conditions similar to those in
the transformation of 3a to 7, the attempted acetalization
of 8 unexpectedly produced benzyl methyl ketone (9) in
high yield.
Acknowledgment
This work was supported by Grants-in-Aid for Scientific Research
and COE Research from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan.
References and Notes
(1) (a) Kolb, M. Synthesis 1990, 171. (b) Yus, M.; Nájera, C.;
Foubelo, F. Tetrahedron 2003, 59, 6147.
(2) Yoshida, S.; Yorimitsu, H.; Oshima, K. J. Organomet.
Chem. 2007, 692, in press; doi: 10.1016/
3.0 equiv H2SO4
O–
j.jorganchem.2006.12.029.
S+
6.0 equiv HOCH2CH2OH
O
(3) Ketene dithioacetal monoxide is known as a Michael
acceptor: (a) Herrmann, J. L.; Kieczykowski, G. R.;
Romanet, R. F.; Wepplo, P. J.; Schlessinger, R. H.
Tetrahedron Lett. 1973, 14, 4711. (b) Nakane, M.;
Hutchinson, C. R. J. Org. Chem. 1978, 43, 3922.
(4) (a) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics
1996, 16, 4229. (b) Fagnou, K.; Lautens, M. Chem. Rev.
2003, 103, 169. (c) Hayashi, T.; Yamasaki, K. Chem. Rev.
2003, 103, 2829. (d) Yoshida, K.; Hayashi, T. In Modern
Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.;
Wiley-VCH: Weinheim, 2005, Chap. 3.
Ph
Ph
toluene, 100 °C, 2 h
S
O
7 84%
3a
1) LDA, –78 °C, 1 h
2) MeI
3.0 equiv H2SO4
6.0 equiv HOCH2CH2OH
O–
S+
O
Ph
Ph
toluene, 100 °C, 1 h
S
Me
Me
8 80%
(single isomer)
(5) Addition to alkenylphosphonates: (a) Hayashi, T.; Senda,
T.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 1999, 121,
11591. (b) Addition to nitroalkenes: Hayashi, T.; Senda, T.;
Ogasawara, M. J. Am. Chem. Soc. 2000, 122, 10716.
9 87%
Scheme 4
Synlett 2007, No. 10, 1622–1624 © Thieme Stuttgart · New York

1624
S. Yoshida et al.
LETTER
(6) Experimental Procedure
(10) We are tempted to assume the stereochemistry of 6b based
on the plausible reaction mechanism shown here
(Scheme 6). Attempts to prepare X-ray-quality crystals of
6b or related compounds are in progress.
The [Rh(OH)(cod)]2 (7.3 mg, 0.016 mmol) was placed in a
flask under an atmosphere of argon. A dioxane (3.0 mL)
solution of 2-methylene-1,3-dithiane 1-oxide (1a, 44.1 mg,
0.30 mmol) and H2O (0.3 mL) were added. Then,
phenylboronic acid (2a, 43.8 mg, 0.36 mmol) was added,
and the mixture was stirred at 25 °C for 3 h. The reaction
mixture was poured into sat. aq NaHCO3 (5 mL) and
extracted with EtOAc (3 × 10 mL). The combined organic
layer was dried over anhyd Na2SO4 and concentrated in
vacuo. Purification by chromatography on a silica gel
column provided 2-benzyl-1,3-dithiane 1-oxide (3a, 65.6
mg, 0.29 mmol, 97%).
[Rh]–
S+
S
S
S+
–
[Rh]
Ph
O
O
O
S
H
S
Ph
H
Me
Me
Ph
H
Me
6b
H
(tentative
structure)
Scheme 6
(7) The product 3a is a known compound. The 1H NMR and 13
C
(11) Ogura, K.; Tsuchihashi, G. Tetrahedron Lett. 1971, 34,
3151.
(12) The relative stereochemistry of 8 has not been determined.
(13) Page, P. C. B.; Shuttleworth, S. J.; McKenzie, M. J.;
Schilling, M. B.; Tapolczay, D. J. Synthesis 1995, 73.
NMR spectra of 3a were identical to the reported data: Page,
P. C. B.; Wilkes, R. D.; Namwindwa, E. S.; Witty, M. J.
Tetrahedron 1996, 52, 2125.
(8) The mechanism for the stereoselective formation of the cis-
product 3a is not clear at this stage. Protonation of the
intermediate shown in Figure 1 would be the key step.
(9) The relative stereochemistry of 5 is not clear.
[Rh]
[Rh]
Bn
S
O
S
S
or
O
S
Bn
Figure 1
Synlett 2007, No. 10, 1622–1624 © Thieme Stuttgart · New York

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