Rhodium catalyzed 1,4-conjugate addition of 1,5-azastibocines with electron deficient olefins

Article abstract of DOI:10.1248/cpb.56.1502

The rhodium-catalyzed reaction of Sb-aryl-1,5-azastibocines with α,β-unsaturated ketones and esters is described. Exclusive formation of 1,4-conjugate adduct was achieved in aqueous NMP (N-methyl-2-pyrrolidinone) in the presence of 5 mol% of [RhCl(cod)]

Full text of DOI:10.1248/cpb.56.1502

1502
Communications to the Editor
Chem. Pharm. Bull. 56(10) 1502—1504 (2008)
Vol. 56, No. 10
Rhodium Catalyzed 1,4-Conjugate
Addition of 1,5-Azastibocines with
Electron Deficient Olefins
partners for soft electrophiles such as a,b-unsaturated car-
bonyl compounds.
For 1,4-conjugate addition, one of the most conventional
and prevailing methods is the use of soft copper reagents
such as organocuprates.7) However, because these reagents
have to be prepared from moisture sensitive organolithiums,8)
Grignard reagents,9) and organozinc reagents,10) the reactions
have to be carried out in strict anhydrous conditions under an
inert atmosphere.
Another method for 1,4-conjugate addition was pioneered
by Miyaura and co-workers using boronic acid in the pres-
ence of rhodium catalysts.11) Inspired by this work, a number
of main group compounds were investigated for the tran-
sition metal catalyzed 1,4-conjugate addition including
organo-aluminum,12) -boron,13) -tin,14) -silicon,15) -bismuth,16)
-indium,17) -plumbum,18) -zirconium19) and -zinc20) com-
pounds. Unlike copper reagents, these compounds exhibit a
tolerance for hard electrophiles such as water and the reac-
tions can be carried out in an aqueous medium.
Naoki KAKUSAWA and Jyoji KURITA*
Faculty of Pharmaceutical Sciences, Hokuriku University;
Kanagawa-machi Ho-3, Kanazawa 920–1181, Japan.
Received May 30, 2008; accepted July 24, 2008; published online
July 30, 2008
The rhodium-catalyzed reaction of Sb-aryl-1,5-azastibocines
with a,b-unsaturated ketones and esters is described. Exclusive
formation of 1,4-conjugate adduct was achieved in aqueous
NMP (N-methyl-2-pyrrolidinone) in the presence of 5 mol% of
[RhCl(cod)]2, and no formation of Heck adduct was observed in
this condition. Reactions with various enones and enoates were
also demonstrated to prove generality of the 1,4-conjugate addi-
tion.
Key words 1,5-azastibocine; 1,4-conjugate addition; rhodium catalyst;
Over the past few years, we have investigated the chem-
istry of organoantimony compounds and revealed that 1,5-
azastibocines (1) with N–Sb intramolecular interaction are
organoantimony compound; main group element; aqueous solvent
Recent advances of metal catalyzed C–C bond formation excellent transmetallating agents in Pd-catalyzed cross-cou-
are remarkable,1) as a result of the development of sophisti- pling reactions.21,22) These results prompted us to investigate
cated ligands of transition metals,2) elaboration of effective 1,4-conjugate addition using 1,5-azastibocines (1) with an
transmetallating agents,3) employment of ionic liquids as re- expectation of mild reaction conditions in aqueous media.
action medium,4) and microwave technology.5) Especially, re-
First, various transition metal catalysts were investigated
search on effective transmetallating agents is a field of atten- for the reaction of Sb-phenyl-1,5-azastibocines (1a) with
tion. With these agents, the transition metal-catalyzed reac- methyl vinyl ketone (2) in 1,4-dioxane : H2O (10 : 1). The re-
tions can be carried out efficiently under mild conditions and action mixture was heated at 100 °C under an argon atmo-
the reactions become applicable to unstable compounds with sphere until almost all the starting material was consumed. In
labile functional groups.
the presence of 5 mol% of palladium catalysts, none of the
Progress in chemistry of main group elements6) con- conjugate adduct (3) was observed and only Heck-type prod-
tributes much to the development of efficient transmetallat- uct (4) was formed (Table 1, entries 1—3). Nickel catalysts
ing agents because main group compounds exhibit suitable are reported to be effective for indium-mediated 1,4-conju-
properties for the metal catalyzed reaction. Particularly, heav- gate addition,23) however, neither NiCl2(PPh3)2 nor Ni(cod)2
ier element compounds below third low show soft nucle- promoted the reaction of 1,5-azastibocine (1a) with methyl
ophilic characteristics, and are considered to be reasonable vinyl ketone (2) and all the starting stibocine (1a) was recov-
Table 1. Investigation of Catalyst and Solvent
Entry
Catalyst
Pd(OAc)2
Solvent
Time (h)
3 (%)b)
4 (%)b)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Dioxane : H2O (10 : 1)
24
24
24
24
16
14
16
9
5.5
3.5
1
1
2.5
1
—
—
—
36
55
78
80
81
70
84
75
76
77
83
74
79
43
14
36
11
—
11
—
—
—
—
6
PdCl2
PdCl2(PPh3)2
Rh(acac)(C2H4)2
Rh(nbd)ClO4
Rh(cod)BF4
[Rh(OH)(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
THF : H2O (10 : 1)
DME : H2O (10 : 1)
C2H5OH
DMU : H2O (10 : 1)
TMU : H2O (10 : 1)
NMP : H2O (10 : 1)
NMP
—
—
9
1
a) Oil bath temperature. b) Isolated yield.
∗ To whom correspondence should be addressed. e-mail: j-kurita@hokuriku-u.ac.jp
© 2008 Pharmaceutical Society of Japan

October 2008
1503
ered unchanged. Under the rhodium catalysts (5 mol%), the the aryl group on antimony and a reduction of the reaction
reaction proceeded efficiently to give the expected 1,4-adduct time.
(3) as the major product (entries 4—8). Especially, rhodium
A possible catalytic cycle for the conjugate addition was
complexes with cod (cyclooctadiene) ligand worked effec- proposed which may be similar to the mechanism for the
tively. Among them, [RhCl(cod)]2 was found to be a suitable 1,4-addition of organoboronic acid to enones (Chart 2).24—26)
catalyst in terms of yield and selectivity of the products (3) The aryl group on 1,5-azastibocine was transmetallated to
(entry 8).
rhodium catalyst to form aryl-rhodium complex (A). Inser-
Next, the most suitable solvent for the reaction was inves- tion of a,b-unsaturated compound then took place to the
tigated by use of [RhCl(cod)]2 as the catalyst. When the reac- aryl-rhodium bond to give h3-oxa-p-allyl rhodium complex
tion was attempted in aqueous ethereal solvents, the conju- (B), which was hydrolyzed with water from aqueous solvent
gate adduct (3) was produced in good yield, although the re- to give 1,4-conjugate adduct (C) and rhodium hydroxide (D).
action required a prolonged time for completion (entries 8— In the aqueous solvent, the hydrolysis process may be more
10). A neutral protic solvent like ethanol was a good alterna- favorable than the b-elimination process. So, no Heck-type
tive to aqueous ethereal solvents (entry 11), while acetic acid
was unsuitable because of decomposition of 1,5-azastibocine
Table 2. Reaction of 1a with Various Enones and Enoates
(1a). Aqueous dipolar solvents were appropriate for the reac-
tion to give the conjugate adduct (3) in good yield in a short
time (entries 12—14). Among them, aqueous NMP (N-
methyl-2-pyrrolidinone) was found to be the best choice of
solvent giving rise to the expected product (3) exclusively in
83% yield in 1 h and no Heck type adduct (4) was observed
(entry 14). Water plays an important role in this reaction.
When the reaction was conducted in dehydrated NMP, Heck
type adduct (4) was formed in 9% yield which was never ob-
served in aqueous NMP (entry 15).
Entry
Electrophile
Conjugate adduct
Yield (%)b)
1
2
80
80
Under this optimized condition, various Sb-aryl-1,5-azasti-
bocines (1a—d) were reacted with methyl vinyl ketone (2)
(Chart 1). Regardless of the electronic nature of the aryl
group, all the 1,4-conjugate addition proceeded in 1 h at
100 °C in good yield. From these results, 1,5-azastibocines
(1) were found to be good aryl donors in the 1,4-conjugate
addition.
The reactions of Sb-phenyl-1,5-azastibocine (1a) with var-
ious enones and enoates were investigated (Table 2). The re-
actions with enone unsubstituted at b-position and with
cyclic enones gave the expected 1,4-adducts in good yield
(entries 1—3). However, the yields of the 1,4-adduct were
decreased in the reaction of enones with bulky substituent at
b-position (entry 4). In the reaction of enoates, steric hinder-
ance of ester moiety did not affect the reaction because
methyl, butyl, and t-butyl esters gave the corresponding 1,4-
adducts in high yield (entries 5—7). However, substituent on
double bond inhibited the 1,4-addition in moderate yield
(entry 8).
3
4
92
59
5
6
84
94
7
8
99
66
a) Oil bath temperature. b) Isolated yield.
Under the [RhCl(cod)]2 catalyst in aqueous NMP, methyl
vinyl ketone (2) also underwent 1,4-conjugate addition with
triphenylstibane (Ph3Sb) which was not activated by in-
tramolecular N–Sb interaction. However, the reaction re-
quired a much longer time (24 h). The intramolecular N–Sb
interaction in 1,5-azastibocine (1) contributed to activation of
Chart 1. Reaction of Various Sb-Aryl-1,5-Azastibocines (1) with Methyl
Vinyl Ketone (2)
Chart 2. Possible Catalytic Cycle

1504
Vol. 56, No. 10
(2007).
adduct (E) was produced and almost exclusive formation of
1,4-conjugate adduct (C) was observed. The rhodium hy-
droxide (D) then underwent transmetallation by 1,5-azasti-
bocine to regenerate aryl-rhodium complex (A).
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Acknowledgements This work is supported in part by a Grant-in-Aid
for Scientific Research from The Ministry of Education, Culture, Sports,
Sciences and Technology (MEXT) of Japan. Financial support by The Spe-
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