Reductive intramolecular cyclization of α-bromo silyl ethers mediated by samarium diiodide

Article abstract of DOI:10.1039/a807736c

A new SmI₂-promoted intramolecular reductive cyclization of β-(α-bromo siloxy) carbonyl compounds is reported.

Full text of DOI:10.1039/a807736c

Reductive intramolecular cyclization of a-bromo silyl ethers mediated by
samarium diiodide
H. S. Park, I. S. Lee, D. W. Kwon and Y. H. Kim*
Department of Chemistry, Korea Advanced Institute of Science and Technology, Taejon 305 - 701 Korea.
E-mail:kimyh@sorak.kaist.ac.kr
Received (in Cambridge, UK) 5th October 1998, Accepted 12th November 1998
A new SmI2-promoted intramolecular reductive cyclization
of b-(a-bromo siloxy) carbonyl compounds is reported.
Br
Si
Si
Si
O
O
i
O
O
R1
HO
R1
In the last decade, SmI2 has become one of the most developed
reagents in organic synthesis due to the oxophilicity of
samarium metal and its powerful one election donor reactivity
with various functional groups.1 Reductions, reductive cycliza-
tions or coupling reactions using SmI2 have been intensively
studied. In particular, intramolecular reductive cyclizations
have brought noticeable results in the formation of highly
functionalized carbocycles1,2 and heterocycles.1,3 Barbier type
reactions,1c,4 Reformatsky type reactions,1c,5 pinacolic coupling
reactions1c,6 and ketone-olefin coupling reactions1b,c,7 have
been investigated for intramolecular reductive cyclization. Aryl
radical cyclization,8 halide induced cyclization,1b,c,9 and se-
quence cyclization1a,10 have also been reported. Of these
reactions, Barbier type reactions give excellent results for
cyclization with high stereoselectivity.1c
Intramolecular cyclizations of b-(a-bromo siloxy) alkenes or
alkynes or vinyl bromo siloxy derivatives via a free radical
process by treatment with Bu3SnH gave various useful cyclic
silyl ethers11 with high degrees of regio-, chemo- and stereo-
selectivity; the reaction products are potentially useful inter-
mediates which can be converted to triols by Tamao oxida-
tion.12
+
R4
R4
HO
R1
R4
R2
R2
R3
R3
R3
R2
2
3
1
Scheme 2 Reagents and conditions: i, SmI2 (2 equiv.), HMPA (4 equiv.),
THF, 278 °C.
Here we describe a new intramolecular reductive cyclizations
of b-(a-bromo siloxy) carbonyl compounds 1 with SmI2 in the
presence of HMPA to 2, as shown in Scheme 2.
In order to generalize the cyclization of b-(a-bromo siloxy)
carbonyl substrates, both acyclic (1a–j) and cyclic substrates
(1k–n) were subjected to the cyclizations under the optimized
reaction conditions [SmI2 (2.2 equiv.), HMPA (4 equiv.), THF,
278 °C]. The results obtained are summarized in Table 1.
Formation of two stereoisomers is possible; one is the syn
isomer, which has the R3 and OH groups pointing in the same
direction, and the other is anti isomer, which has the R3 and OH
groups pointing in opposite directions. As a result the syn
isomer 2 was obtained together with trace amount of the anti
isomer 3. The configuration of 2 (2f) was identified by 1H and
13C NMR and NOE experiments (Fig. 1) and mass spectros-
copy. The syn isomer conformation obtained could be explained
by steric hindrance in the transition state. In the four possible
transition states, conformation A seems to be the most favorable
due to steric effects, as suggested by Molander.9
Although many attempts have been made to construct
functionalized carbocycles or heterocycles by ring closure of a
ketyl radical or anion with a ketene or alkyne, there is no
reported example of radical or anion cyclization of b-(a-bromo
siloxy) carbonyl derivatives mediated by SmI2. Matsuda and
co-workers examined cyclization of b-(a-bromo siloxy) car-
bonyl derivatives in sugar moieties, and demonstrated that no
cyclization occurred.13
In the absence of HMPA, the yield of 2 is low and desilylated
aldol products were obtained as the major product. Erythro or
threo cyclohexanone substrates gave the corresponding erythro
or threo products respectively in good yields. The substrate 1d
gave the desired cyclized product 2d (44%) together with olefin
We were intrigued by the possibility of another Barbier type
reaction, this time with b-(a-bromo siloxy) carbonyl substrates
using SmI2. The b-(a- bromo siloxy) carbonyl substrates were
prepared via two steps as shown in Scheme 1. The ketones were
condensed with aldehydes or ketones under typical aldol
conditions.14 For the preparation of a-substituted aldol prod-
a
Table 1 Cyclization of siloxy derivatives using SmI2
Ratio
t/min 2:3
Yield
(%)b
ucts, Bun BOTf was used and the erythro product was obtained
Substrate R2
R1
R3
R4
2
as the major product. The resulting b-hydroxy ketone was
treated with bromomethyl(dimethyl)chlorosilane in the pres-
ence of pyridine at 0 °C to provide the desired product 1 in
excellent yields as shown in Scheme 1. Their structures were
identified by 1H and 13C NMR and mass spectroscopy.
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
H
H
H
H
H
Me
Me
Me
Me
Me
–(CH2)4–
H
–(CH2)3–
–(CH2)3–
Ph
Ph
Me
Pri
Me
Et
Et
Et
Ph
Ph
H
H
H
H
H
H
K
H
H
H
H
Et
Pr
Pr
Pr
10
15
30
30
> 99:1 61
> 99:1 75
> 99:1 72
> 99:1 44c
> 99:1 57
95:5 65 (15)d
90:10 67
95:5 62
92:8 71
95:5 35
c-Hex 30
Ph
Pr
But
H
Ph
Ph
30
30
30
15
10
10
10
10
30
Br
O
Si
O
OH
R3
R3
i,iii or ii,iii
iv
O
O
> 99:1 74
> 99:1 69
> 99:1 80
> 99:1 63
R1
R1
R4
–(CH2)4– Ph
H
H
R1
R4
R2
R2
Ph
Et
R3
R2
a All reactions were carried out using SmI2 (2.2 equiv.) in THF and HMPA
(4 equiv.) at 278 °C. b Isolated yields. c Eliminated olefin was obtained in
ca. 20% yield. d The reaction was carried out in the absence of HMPA.
Scheme 1 Reagents and conditions: i, LDA, THF, 278 °C; ii, Bun2BOTf,
Pri2NEt, THF, 278 °C; iii, R4CHO, 278 °C; iv, ClMe2SiCH2Br, pyridine,
CH2Cl2, 0 °C.
Chem. Commun., 1998, 2745–2746
2745

2.0%
The a-effect of the silicon moiety may also help to promote
the organosamarium pathway. Most of the reactions gave the
reduced aldol products in ca. 20% yield as a side product.
Formation of the aldol side product also supports the organosa-
marium pathway. If the reaction occurs via a diradical pathway,
the carbonyl moiety might be reduced to a b-OH moiety.
However, only the desilylated aldol products (up to 20%) were
obtained and confirmed.
R2
O
2.5%
CH3
O
R1
CH2CH3
CH3
_
R3
H
H
R4
Ph
SmI2
O
Si
Si
OH
H
CH3
A
Fig. 1 NOE correlations of b-hydroxy cyclic silyl ether.
The authors acknowledge the financial support of the Korea
Research Foundation.
Si
O
HO
Notes and references
Br
1 (a) G. A. Molander and C. R. Harris, Tetrahedron, 1998, 55, 3321; (b)
G. A. Molander and C. R. Harris, Chem. Rev., 1996, 96, 307; (c) G. A.
Molander, Chem. Rev., 1992, 92, 29; B. M. Trost, Comprehensive of
Organic Synthesis, 1991, vol. 1, p. 235; (d) J. A. Soderquist,
Aldrichchim. Acta., 1991, 24, 15; (e) H. B. Kagan and J. L. Namy,
Tetrahedron, 1986, 42, 6573.
Si
2d
O
O
i
+
OH
1d
2 G. A. Molander and C. R. Harris, J. Org. Chem., 1997, 62, 2944; G. A.
Molander and C. del Pozo, J. Org. Chem.,1997, 62, 2935; G. A.
Molander and C. R. Harris, J. Org. Chem., 1997, 62, 7418; C. F. Sturino
and A. G. Fallis, J. Am. Chem. Soc., 1995, 116, 7447; Z. Zhou and S. M.
Bennett, Tetrahedron Lett., 1997, 1153.
3 D. C. Ha, C. S. Yun and E. Yu, Tetrahedron Lett., 1996, 37, 2577; J. E.
Baldwin and M. G. Moloney, Tetrahedron, 1994, 50, 9411; J. M.
Aurreoechea and M. S. Spizua, Heterocycles, 1994, 37, 223; S. I.
Fukuzawa and T. Tsuchimoto, Synlett, 1993, 803.
4 G. A. Molander and C. R. Harris, J. Am. Chem. Soc., 1997, 117, 3705;
G. A. Molander and J. A. Mckie, J. Org. Chem., 1991, 56, 4112.
5 G. A. Molander, J. B. Etter and L. S. Harry, J. Am. Chem. Soc., 1991,
113, 8036.
6 M. Carpiatero, A. F. Mayorals and C. Jaramillo, J. Org. Chem., 1997,
62, 1916; T. Wirth, Angew. Chem., Int. Ed. Engl., 1996, 35, 61; J. L.
Chiara, W. Cabri and S. Hanessian, Tetrahedron Lett., 1991, 32,
1125.
7 G. A. Molander and C. L. Pozo Losada, J. Org. Chem., 1997, 62, 2935;
M. K. Schwarbe and R. P. Little, Synth. Commun., 1997, 27, 837; G. A.
Molander and S. R. Shakya, J. Org. Chem., 1996, 61, 5885; T. K. Sarkar
and S. K. Nancy, Tetrahedron Lett., 1996, 37, 5195.
8 J. M. Arrecoechea, A. Arricta and F. P. Cossio, J. Org. Chem., 1997, 62,
1125; M. Murakami, M. Hayashi, Y. Ito, F. Pallemer, J. Collin and
H. B. Kagan, Appl. Organomet. Chem., 1995, 9, 385; D. P. Curran and
M. J. Totleben, J. Am. Chem. Soc., 1992, 114, 6050; D. P. Curran and
P. Wipf, J. Org. Chem., 1992, 57, 1740.
9 Z. Zhou, D. Larouche and S. M. Bemelt, Tetrahedron, 1995, 51, 11623;
C. F. Stariro and A. G. Fallis, J. Am. Chem. Soc., 1994, 116, 7447;
G. A. Molander and J. A. Mckie, J. Org. Chem., 1993, 58, 7126.
10 T. Skrydstrup, Angew. Chem., Int. Ed. Engl., 1997, 36, 345.
11 S. Bogen, M. Journet, and M. Malacria, Synth. Commun., 1994, 24,
1215; M. Journet, W. Smadja and M. Malacria, Synlett, 1991, 320; M.
Koreeda and L. G. Hanmann, J. Am. Chem. Soc., 1990, 112, 8175; K.
Tamao, K. Maeda, T. Yamaguchi and Y. Ito, J. Am. Chem. Soc., 1989,
111, 4984.
12 K. Tamao, N. Ishida, T. Tanaka and M. Kumada, Organometallics,
1983, 2, 1694. The product 1l was smoothly converted into the triols in
70% yield via Tamao oxidation. The structure was determined by 1H
NMR and EI mass spectroscopy (m/z 236, 85%).
4
Scheme 3 Reagents and conditions: i, SmI2 (2.2 equiv.), HMPA (4 equiv.),
THF, 278 °C.
4 (20%) which is formed by elimination of the siloxy moiety as
shown in Scheme 3.
In the reaction mechanism, there are two possible process; a
radical–radical coupling process and a samarium Grignard-type
anion process (Scheme 4). In the radical–radical coupling
reaction, 2 equiv. of SmI2 generates both a ketyl radical and an
alkyl radical which couple each other. On the other hand, the
organosamarium Grignard-type species, which could be gen-
erated from an alkyl radical by one more electron transfer from
SmI2, could add to the carbonyl group. Since the reactivity of
primary alkyl bromides with SmI2 is higher than that of
carbonyl groups, it can be considered that the organosamarium
Grignard-type process is more favorable.
Br
Si
O
Si
HO
R1
O
O
2 SmI2
R4
R1
R4
R2
2a
R3
R3
R2
1
H+
2 SmI2
I2Sm
O
Si
Si
O
O
I2SmO
R1
R4
R1
R4
13 S. Ichikawa, S. Shuto, N. Minakawa and A. Matsuda, J. Org. Chem.,
1997, 62, 1368.
14 D. A. Evans, E. Vogel and J. V. Nelson, J. Am. Chem. Soc., 1979, 101,
6120.
R2
R3
R3
R2
Scheme 4
Communication 8/07736C
2746
Chem. Commun., 1998, 2745–2746