Desymmetrization of 4-dimethylsiloxy-1,6-heptadiynes through sequential double silylformylation.

Article abstract of DOI:10.1021/ol0156594

[reaction in text] Desymmetrization of dimethylsilyloxyalkadiynes (1) by Rh-catalyzed intramolecular silylformylation affords 5-exo-(formylmethylene)oxasilacyclopentanes 2 in high yields. Novel sequential double silylformylation of 1a also provides desymm

Full text of DOI:10.1021/ol0156594

ORGANIC
LETTERS
2001
Vol. 3, No. 9
1303-1305
Desymmetrization of
4-Dimethylsiloxy-1,6-heptadiynes
through Sequential Double
Silylformylation
Dominique Bonafoux and Iwao Ojima*
Department of Chemistry, State UniVersity of New York at Stony Brook,
Stony Brook, New York 11794-3400
iojima@notes.cc.sunysb.edu
Received February 5, 2001
ABSTRACT
Desymmetrization of dimethylsilyloxyalkadiynes (1) by Rh-catalyzed intramolecular silylformylation affords 5-exo-(formylmethylene)-
oxasilacyclopentanes 2 in high yields. Novel sequential double silylformylation of 1a also provides desymmetrization, giving 3-(3-silyl-2-
formylprop-2-enyl)-5-exo-(formylmethylene)oxasilacyclopentanes 4 in excellent yields. Reduction of 2a and 4 with NaBH4 gives the corresponding
5-exo-(hydroxymethylmethylene)oxasilacyclopentanes 3a and 5, respectively.
Silylformylation of alkynes catalyzed by Rh and Co-Rh
complexes has been extensively studied in the past decade
and provides a powerful method for the regio- and stereo-
selective syntheses of â-formylvinylsilanes.1-6 The reaction
has been applied to the efficient synthesis of pyrrolizidine
alkaloids and other organic syntheses.1d,2b,7,8 The silylformyl-
ation of 1-alkynes gives (Z)-1-silyl-2-formyl-1-alkenes with
complete regio- and stereoselectivity.1-4 However, this means
that it is practically impossible to obtain the products with
opposite regiochemistry, i.e, (Z)-2-silyl-1-formyl-1-alkenes.
The control of regioselectivity is, however, difficult for the
reaction of simple internal alkynes.2 To solve this problem,
the intramolecular silylformylation of 1-alkynes and internal
alkynes has been successfully developed by introducing a
dimethylsiloxy, i.e., HMe2SiO, moiety as the directing
group.5 A similar reversal of selectivity was achieved by
introducing a HSiR2 moeity to the alkyl terminal carbon of
alkynes.6 Intramolecular silylformylation of ω-hydrosiloxy-
alkenes has also been developed using Rh(acac)(CO)2 as
catalyst under very high pressure of CO (68 atm).9 We
(1) (a) Ojima, I.; Ingallina, P.; Donovan, R. J.; Clos, N. Organometallics
1991, 10, 38. (b) Ojima, I.; Donovan, R.; Ingallina, P.; Clos, N.; Shay, W.
R.; Egushi, M.; Zeng, Q.; Korda, A. J. Cluster Sci. 1992, 3, 423. (c) Egushi,
M.; Zeng, Q.; Korda, A.; Ojima, I. Tetrahedron Lett. 1993, 34, 915. (d)
Ojima, I.; Donovan, R. J.; Egushi, M.; Shay, W. R.; Ingallina, P.; Korda,
A.; Zeng, Q. Tetrahedron 1993, 49, 5431. (e) Ojima, I.; Li, Z.; Donovan,
R. J.; Ingallina, P. Inorg. Chim. Acta 1998, 270, 279. (f) Ojima, I.; Li, Z.;
Zhu, J. In The Chemistry of Organic Silicon Compounds; Rappoport, Z.,
Apaloig, Y.; Ed.; John Wiley & Son: New York, 1998; Chapter 29, p 1687.
(2) (a) Matsuda, I.; Ogiso, A.; Sato, S.; Izumi, Y. J. Am. Chem. Soc.
1989, 111, 2332. (b) Matsuda, I.; Ogino, A.; Sato, S. J. Am. Chem. Soc.
1990, 112, 6120. (c) Matsuda, I.; Sakakibara, J.; Nagashima, H. Tetrahedron
Lett. 1991, 32, 7431. (d) Matsuda, I.; Sakakibara, J.; Inoue, H.; Nagashima,
H. Tetrahedron Lett. 1992, 33, 5799. (e) Matsuda, I.; Fukuta, Y.;
Tsuchihashi, T.; Nagashima, H.; Itoh, K. Organometallics 1997, 16, 4327.
(3) (a) Doyle, M. P.; Shanklin, M. S. Organometallics 1993, 12, 11. (b)
Doyle, M. P.; Shanklin, M. S. Organometallics 1994, 13, 1081.
(4) Zhou, J. Q.; Alper, H. Organometallics 1994, 13, 1586.
(7) Ba¨rfacker, L.; Hollmann, C.; Eilbracht, P. Tetrahedron 1998, 54,
4493.
(8) Eilbracht, P.; Hollmann, C.; Schmidt, A. M.; Ba¨rfacker, L. Eur. J.
Org. Chem. 2000, 7, 1131.
(5) Ojima, I.; Vidal, E.; Tzamarioudaki, M.; Matsuda, I. J. Am. Chem.
Soc. 1995, 117, 6797.
(6) Monteil, F.; Matsuda, I.; Alper, H. J. Am. Chem. Soc. 1995, 117,
4419.
(9) Leighton, J. L.; Chapman, E. J. Am. Chem. Soc. 1997, 119, 12416.
10.1021/ol0156594 CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/04/2001

describe here our preliminary results on the successful
desymmetrization of dimethylsiloxyalkadiynes based on Rh-
catalyzed silylformylation, as well as a novel sequential
double silylformylation protocol.
double silylformylation of 1a should take place in the
presence of 1 equiv of a hydrosilane to give 3-(3-silyl-2-
formylprop-2-enyl)-5-exo-(formylmethylene)-oxasilacyclo-
pentane 4 (Table 1). In fact, the reaction of 1a catalyzed by
Desymmetrization of Dimethylsiloxyalkadiynes. Intra-
molecular silylformylation of 4-dimethylsiloxy-1,6-hepta-
diyne (1a) catalyzed by Rh(acac)(CO)2 (0.5 mol %) in
toluene (0.072 M) at 25 °C and 10 atm of CO proceeded
smoothly to give 5-exo-(formylmethylene)oxasilacyclo-
pentane 2a in 98% yield (Scheme 1). When the reaction was
Scheme 3. Mechanism of the Double Silylformylation of 1a
with PhMe2SiH
Scheme 1. Desymmetrization of
4-Dimethylsiloxy-1,6-heptadiyne (1a) by Rh-Catalyzed
Intramolecular Silylformylationa
a (i) Rh(acac)(CO)2, CO (10 atm), toluene, rt, 16 h, 98%; (ii)
NaBH4, MeOH, O °C, 50 min, 70%.
carried out under 1-5 atm of CO, intramolecular hydro-
silylation of 1a took place in addition to the desired
silylformylation. Since 2a was found to be unstable for
purification through a silica gel column, it was reduced to
the corresponding alcohol 3a using NaBH4 in methanol (70%
isolated yield after purification though silica gel column).
In a similar manner, the reaction of 5-dimethylsiloxy-2,7-
nonadiyne (1b) at 60 °C and 20 atm of CO cleanly gave the
corresponding intramolecular silyformylation product 2b in
82% isolated yield, which was stable for chromatographic
purification on silica gel (Scheme 2).
Scheme 2. Desymmetrization of the
5-Dimethylsiloxy-2,7-nonadiyne (1b) by Rh-Catalyzed
Intramolecular Silylformylationa
a (i) Rh(acac)(CO)2, CO (20 atm), toluene, 60 °C, 16 h, 82%.
Rh(acac)(CO)2 (0.5 mol %) in the presence of HSiMe2Ph or
HSiEt3 at 25 °C and 10 atm of CO proceeded smoothly to
give 4 (R3Si ) (a) PhMe2; (b) Et3Si) in quantitative yield.
The reaction using a bulky and less reactive hydrosilane,
HSiMe2 Bu, required 50 °C for 24 h to complete, affording
4c in excellent yield. Results are summarized in Table 1.
To establish the mechanism of this double silylformylation,
the reaction of 1a in the presence of the most reactive silane
(Me2PhSiH) was monitored by 1H NMR. The integration of
These reactions have achieved the desymmetrization of
siloxyalkadiynes to give highly functionalized useful syn-
thetic intermediates 2a and 2b, which can readily be further
manipulated at the unreacted acetylene moiety as well as
the R,â-unsaturated aldehyde moiety. It is obvious that after
appropriate reduction of the aldehyde moiety the subsequent
Tamao oxidation10 of these compounds would lead to the
formation of the corresponding 1,3,5-triols.11
t
(10) (a) Tamao, K.; Tohma, T.; Inui, N.; Nakayama, O.; Ito, Y.
Tetrahedron Lett. 1990, 31, 7733. (b) Tamao, K.; Nakajima, T.; Sumiya,
R.; Arai, H.; Higushi, N.; Ito, Y. J. Am. Chem. Soc. 1986, 108, 6090. (c)
Graeme, R. J.; Landais, Y. Tetrahedron 1996, 52, 7599.
Desymmetrization of 1a via Sequential Double Silyl-
formylation. If the intramolecular silylformylation of 1a is
much faster than the intermolecular reaction, the sequential
(11) Zacuto, M. J.; Leighton J. L. J. Am. Chem. Soc. 2000, 122, 8587.
1304
Org. Lett., Vol. 3, No. 9, 2001

molecular reaction). This scrambling clearly indicates that
H-D exchange takes place at a certain intermediate in the
catalytic cycle. We propose a catalyst cycle that can
accommodate the observed results in Scheme 3. Cycle 1
depicts the intramolecular reaction, and cycle 2 the inter-
molecular reaction. It is very likely that the observed H-D
exchange takes place at the intermediate C, where PhMe2-
SiD can react with C instead of 1a through σ-bond metathesis
(see transition state I) to form PhMe2SiH and deuterated 2a
after reductive elimination. When PhMe2SiH thus generated
is involved in cycle 2, it leads to the formation of nondeu-
terated aldehyde moiety. When the concentration of 1a is
sufficient enough, the resulting PhMe2Si[Rh]H does not react
with the unreacted acetylene moiety of 2a to go into cycle
2 but rather reacts with 1a to regenerate A and go back to
cycle 1 through σ-bond metathesis (see transition state II).
This is due to the fact that 1a has a much stronger affinity
to Rh-catalyst species than PhMe2SiH(D) because of its two
acetylene groups. It is reasonable to assume that PhMe2-
SiH(D) would start competing with 1a when the concentra-
tion of 1a is decreased as the intramolecular reaction
proceeds.
Table 1. Sequential Double Silylformylation of
4-Dimethylsilyl-1,6-heptadiyne 1aa
hydrosilane
conditions
4 (%)b
5 (%)c
a
b
c
PhMe2SiH
Et3SiH
tBuMe2SiH
rt, 8 h
rt, 18 h
50 °C, 24 h
100
100
98
56
74
62
a Conditions: (i) R3SiH, Rh(acac)(CO)2, CO (10 atm), toluene; (ii)
NaBH4, MeOH, 0 °C. b GC yield using methylene chloride as external
standard. c Isolated yield.
the aldehyde signals at δ 9.5 (d, 3J ) 4.12 Hz, intramolecular
silylformylation) and δ 9.7 (s, intermolecular silylformyl-
ation) as well as the integration of the signal corresponding
In conclusion, the desymmetrization of dimethylsilyloxy-
alkadiynes 1 by Rh-catalyzed intramolecular silylformylation
and novel sequential double silylformylation of 1a was
successfully achieved to afford highly functionalized useful
synthetic intermediates, oxasilacyclopentanes 2 and 4.
4
to the unreacted terminal alkyne at δ 2.0 (t, J ) 2.5 Hz)
allowed an accurate determination of the composition of the
reaction mixture at a given time. It was found that during
the first 2 h of the reaction, the intramolecular silylformyl-
ation proceeded exclusively, affording 2a. Once the intramo-
lecular reaction had completed (t g 2 h), the intermolecular
reaction took place to give 4a. Thus, this transformation can
be called “sequential double silylformylation”.
Acknowledgment. This research was supported by grants
from the National Institutes of Health (NIGMS) and the
National Science Foundation. Generous support from Mit-
subishi Chemical Corp. is gratefully acknowledged.
To look into the mechanism of the unique sequential
double silylformylation process, a labeling experiment was
performed using PhMe2SiD. Then, rather unexpectedly, the
deuterium incorporation to both aldehyde moieties was
observed (35% to the aldehyde arising from the intra-
molecular silylformylation and 65% to that from the inter-
Supporting Information Available: The characterization
datas of compounds 2-5. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL0156594
Org. Lett., Vol. 3, No. 9, 2001
1305