Diastereoselective synthesis of seven-membered-ring trans-alkenes from dienes and aldehydes by silylene transfer

Article abstract of DOI:10.1021/ja305713v

Silver-catalyzed silylene transfer to alkenes forms vinylsilacyclopropanes regioselectively. These allylic silanes undergo additions to aldehydes to form seven-membered-ring trans-alkenes with high diastereoselectivity. The high reactivity of the trans-alkenes is evidenced by their formal [1,3]-sigmatropic rearrangement reactions and the rapid additions of oxygen-hydrogen bonds across the carbon-carbon double bonds.

Full text of DOI:10.1021/ja305713v

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Communication
Diastereoselective Synthesis of Seven-Membered Ring trans-
Alkenes from Dienes and Aldehydes by Silylene Transfer
Margaret A Greene, Michel Prévost, Joshua Tolopilo, and Keith A. Woerpel
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja305713v • Publication Date (Web): 11 Jul 2012
Downloaded from http://pubs.acs.org on July 16, 2012
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Diastereoselective Synthesis of Seven-Membered
Ring trans-Alkenes from Dienes and Aldehydes by
Silylene Transfer
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Margaret A. Greene,† Michel Prévost,‡ Joshua Tolopilo, and K. A. Woerpel*
Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003 USA
Supporting Information.
a
single diastereomer (as determined by 1H NMR
ABSTRACT: Silver-catalyzed silylene transfer to alkenes
formed vinylsilacyclopropanes regioselectively. These
allylic silanes underwent additions to aldehydes to form
spectroscopy).21 This seven-membered ring trans-alkene was
highly reactive: attempts to isolate alkene 4a led to addition
reactions (vide infra). Even in the absence of additional
reagents, the trans-cycloalkene 4a underwent formal [1,3]-
sigmatropic rearrangement over several hours to form an
oxasilacyclopentane (5a) that could be isolated and purified.
seven-membered
ring
trans-alkenes
with
high
diastereoselectivity. The high reactivity of the trans
alkenes is evidenced by their formal [1,3]-sigmatropic
rearrangement reactions and their rapid additions of
oxygen–hydrogen bonds across the carbon–carbon double
bonds.
Scheme 1. One-flask synthesis of seven-membered ring
trans-alkenes.
t-Bu
t-Bu
Si
2
Me
Me
t-Bu
Me
Me
t-Bu
Si
Investigations of the chemistry of seven-membered ring
trans-alkenes have been limited by the difficulty of making
such highly strained alkenes.1 The development of methods
for the synthesis of seven-membered cyclic trans-alkenes
should lead to useful applications of these strained
compounds, considering that advances in the preparation of
the larger eight- and nine-membered ring trans-alkenes have
enabled these highly reactive compounds to be used in
synthesis2,3,4,5 and bioconjugation.6 In contrast to the larger
cyclic trans-alkenes, however, no methods have been
developed for the synthesis of functionalized seven-membered
ring cyclic trans-alkenes. Photo-isomerization of cis-
cycloheptene provides minute quantities of the trans isomer,
which was unstable at –30 ˚C.7 Trapping of transient trans-
cycloheptenes has not proven to be synthetically useful,8,9 and
syntheses of seven-membered ring trans-alkenes containing
heteroatoms in the ring are lengthy and not general.10,11
AgCO2CF3
(1 mol %)
99% (NMR)
1a
3a
H
Me
Me
Me
22 ˚C
67%
(overall
isolated
yield)
H
Si
Me
Ph
PhCHO
t-Bu
O
O
H
Ph
Si
t-Bu
99%
(NMR)
t-Bu
t-Bu
4a
5a
A number of seven-membered ring trans-alkenes can be
synthesized using different substituted dienes and aldehydes
(eq 1, Table 1). In all cases, the silylene transfer reaction was
regioselective and complete in less than ten minutes, and the
addition to the aldehyde was diastereoselective and rapid (less
than ten minutes, except for branched alkyl aldehydes, which
required three hours). Silylene transfer to (E)-1-
(triisopropylsiloxy)-1,3-butadiene (diene 1c) occurred at the
less electron-rich double bond even though silylene transfer
generally occurs to the more electron-rich alkene.22 The
resulting vinylsilacyclopropane, however, reacted not as the
enol ether, but as the allylic silane.15,23
In this Communication, we report a one-flask synthesis of
seven-membered ring trans-alkenes by regioselective,
catalytic silylene transfer to a diene followed by a rapid
diastereoselective addition of an aldehyde. Initial studies
indicate that these strained alkenes are highly reactive.
Our diastereoselective synthesis of seven-membered ring
trans-alkenes was predicated on the high reactivity of strained
allylic silanes with aldehydes.12,13,14,15 The preparation of the
requisite allylic silane (such as 3a, Scheme 1) could be
challenging because it required a formal [2+1] cycloaddition
of a silylene with a diene instead of the formal [4+2]
cycloaddition that is typically observed.16,17,18,19 The silver-
catalyzed silylene transfer reaction to diene 1a, however, gave
vinyl silacyclopropane 3a regioselectively (Scheme 1).20 After
the silylene transfer reaction was complete (less than ten
minutes), one equivalent of benzaldehyde was added, and
within ten minutes, the allylic silane underwent quantitative
insertion of an aldehyde to afford the cyclic trans-alkene 4a as
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Page 2 of 4
O
2
AgCO2CF3;
t-Bu
R1
H
R1
t-Bu
R1
Me
Ph
1
2
3
∆
Si
R2
R3
2(1)
R3
O
Me
t-Bu
Ph
H
H
Si
R
Si
(3)
t-Bu
O
t-Bu
Me
O
Si
R2
R3CHO
t-Bu
8
H
7
Me
1
4
5
t-Bu
t-Bu
4
5
6
7
8
9
The formation of the trans double bond in the seven-
membered ring can be explained by considering the
mechanism of insertion of the aldehyde. The Lewis acidic
silicon atom.12,13,27,28 of the vinylsilacyclopropane intermediate
enables complexation of the aldehyde. Cyclization through
closed, chair-like transition state14,15,29 A would form the
observed trans double bond in the product (eq 4).
Table 1. Formation and rearrangement of trans-oxasilacycloheptene
entry
R1
Me
H
R2
R3
Ph
4
a
b
c
%
99
99
99
75
84
5
a
b
c
%
1
2
3
4
5
Me
67a
51a
99b
80b
86b
Me
Ph
H
OTIPS
OTIPS
OTIPS
Ph
10
11
12
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H
i-Pr
d
e
d
e
H
H
H
(E)-
OTIPS
Ph
t-Bu
OTIPS
Ph
CHCHCH3
O
H
O
H
Si
Si
(4)
t-Bu
6
H
OTIPS
CHCH3Ph
f
75
f
71b
t-Bu
t-Bu
B (= 4c)
a ∆ = room temperature, isolated yield. b ∆ = 60 ˚C, 1H NMR yield
based on comparison to mesitylene internal standard.
A
The highly organized transition state for the insertion also
enables the mutual kinetic of
resolution30
The stereochemical configuration of the seven-membered
a
1
ring trans-alkene was determined by H NMR spectroscopy
vinylsilacyclopropane and a chiral aldehyde. Insertion of
racemic 2-phenylpropanal into the silacyclopropane derived
from a silyloxydiene 1c provided trans-oxasilacycloheptene 4f
as a single diastereomer (Table 1, entry 6). The X-ray crystal
and is consistent with the high reactivity of these compounds
(vide infra). The vinyl protons of the unstable seven-
membered ring trans-alkenes couple with coupling constants
ranging from J = 17.2-17.6 Hz. These values are consistent
with the reported coupling constants of trans-cycloheptene
measured by low temperature NMR spectroscopy (J = 18 Hz).7
structure
obtained
after
rearrangement
to
the
oxasilacyclopentane revealed that the mutual kinetic resolution
matched (S)-2-phenylpropanal with (S)-vinylsilacyclopropane
3c (and the (R)-isomers with each other). Formation of this
diastereomer is consistent with Felkin–Anh addition to the
aldehyde, which minimizes syn-pentane interactions31 (as
shown for the (S,S)-pair in eq 5).
In contrast, the vinyl protons of
a
stable cis-
oxasilacycloheptene exhibit a much smaller coupling constant
(J = 10.9 Hz).16 Nuclear Overhauser Effect experiments are
consistent with the assignment of the alkene geometry and the
overall conformational preference depicted for compounds 4:
irradiation of each vinyl proton leads to NOE enhancements to
substituents on opposite faces of the ring. Further evidence
for the stereochemical assignment results from cleavage of the
silicon–oxygen bond and isolation of the stable allylic silane 6,
which exhibits coupling between the vinylic protons (J = 15.2
Hz) that is consistent with other (E)-allylic silanes.24,25
H
H
H
Me
Me
t-Bu
OTIPS
H
Ph
OTIPS
O
H
Si
O
H
t-Bu
(5)
Si
H
Ph
D (= 4f)
t-Bu
t-Bu
C
Preliminary studies revealed the high reactivity of the
alkenes formed by these new reactions. Attempts to purify
trans-alkene 4a by silica gel chromatography resulted in the
regioselective and stereoselective hydration of the double
bond (Scheme 2). Acetic acid also added selectively across
trans-cycloheptene 4a (Scheme 2).32 The double bond of the
H
H
t-Bu
H
OAc
OTIPS
Ph
n-Bu4NF;
t-Bu
Si
Ph
(2)
O
Si
AcO
Ac2O, NEt3,
DMAP
t-Bu
H
t-Bu
H
OAc
4c
6
oxasilacyclopentane 5c
also
underwent
a
highly
Although the seven-membered ring trans-alkene products
hydrolyzed readily upon handling, they isomerized slowly to a
product that could be isolated and purified (alkene 5, eq 1).
This [1,3]-silyl rearrangement to a stable oxasilacyclopentene,
which would be expected to require high temperatures (500
°C),26 occurred readily at room temperature in most cases. In
the case of the trans-alkene derived from 3-methylpentadiene,
isomerization did not occur, which is likely because this
product would be sterically congested (eq 3). The half-lives
for the formal [1,3]-sigmatropic rearrangement at room
temperature average ten to twelve hours. The rearrangement
stereoselective reaction: when it was treated with MCPBA, a
single diastereomer of the trans-fused epoxide 9 was formed
(eq 6). The oxasilacyclopentane likely underwent epoxidation
followed by acid-catalyzed rearrangement to the eight-
membered ring trans-alkene33 then rapid epoxidation of this
strained carbon–carbon double bond.
Scheme 2. Reactivity of the seven-membered ring trans-
alkene 4a.
H
Me
H
Me
Ph
silica gel
HO
t-Bu
from
seven-membered
ring
trans-alkene
to
H
O
H
Me
Si
50%
from diene
oxasilacyclopentane is likely a thermal process, because
irradiation under a UV lamp (254 nm) did not accelerate the
rearrangement. On the other hand, heating the trans-alkenes
at 60 ˚C reduced the half-life to 30 minutes and improved its
yield (Table 1). The ease of this transformation compared to
known 1,3-silyl rearrangements26 provides additional
confirmation that the cyclic trans-alkene is highly strained.
Me
Ph
t-Bu
9
O
Si
t-Bu
H
H
AcOH
t-Bu
Me
4a
H
Me
Ph
36%
from diene
AcO
t-Bu
O
H
Si
t-Bu
10
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Journal of the American Chemical Society
H
6. Taylor, M. T.; Blackman, M. L.; Dmitrenko, O. Fox, J. M. J.
Am. Chem. Soc. 2012, 133, 9646–9649.
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Lett. 1989, 30, 6805–6808.
8. Hoffmann, R. Inoue, Y. J. Am. Chem. Soc. 1999, 121, 10702–
O
MCPBA
1
2
3
4
5
H
Si
OTIPS
Ph
OTIPS
(6)
t-Bu
O
t-Bu
O
O
Ph
Si
H
t-Bu
t-Bu
5c
11
10710.
9. Bogen, S.; Fensterbank, L. Malacria, M. C. R. Acad. Sci. II C
2001, 4, 423–426.
In conclusion, we have developed a rapid synthesis of
seven-membered ring trans-alkenes by single-flask
6
a
10. Krebs, A.; Pforr, K.-I.; Raffay, W.; Thölke, W. A.; Hardt, I.
Boese, R. Angew. Chem., Int. Ed. Engl. 1997, 36, 159–160.
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14182–14183.
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T.; Koetzle, T. F.; Mason, S. A. Albinati, A. Organometallics 1999,
18, 3921–3932.
19. For examples of stable vinylsilacyclopropanes, see: Zhang, S.;
Wagenseller, P. E. Conlin, R. T. J. Am. Chem. Soc. 1991, 113, 4272-
4278.
20. These vinylsilanes were stable as long as they were protected
from oxygen and water. No isomerization to silacyclopentenes, the
product of a formal [4+2] cycloaddition, was observed.
21. A control experiment suggested that silver trifluoroacetate
plays no role in the reaction with the aldehyde. Addition of
tetramethylethylenediamine, which should complex silver (Comuzzi,
C.; Novelli, R.; Portanova, R.; Tolazzi, M. Supramol. Chem. 2001,
13, 455–460), before addition of aldehyde had no impact on the
insertion reaction.
22. Driver, T. G. Woerpel, K. A. J. Am. Chem. Soc. 2003, 125,
10659–10663.
23. This methodology can be employed on a preparative scale:
trans-oxasilacycloheptene 4c was prepared on a 1 mmol scale
during the preparation of allylic silane 6. Details are provided as
Supporting Information.
24. Alberts, V.; Cuthbertson, M. J.; Hawker, D. W. Wells, P. R.
Org. Magn. Resonance. 1984, 22, 556–560.
25. Acyclic (Z)-allylic silanes show coupling constants between
10.7 and 11.0 Hz, whereas (E)-allylic silanes exhibit coupling
constants between 14.9 and 15.2 Hz: see Smitrovich, J. H. Woerpel,
K. A. J. Org. Chem. 2000, 65, 1601–1614.
26. Slutsky, J. Kwart, H. J. Am. Chem. Soc. 1973, 95, 8678–8685.
27. Denmark, S. E.; Jacobs, R. T.; Dai-Ho, G. Wilson, S.
Organometallics 1990, 9.
28. Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X. Leighton,
J. L. J. Am. Chem. Soc. 2002, 124, 7920–7921.
29. Zimmerman, H. E. Traxler, M. D. J. Am. Chem. Soc. 1957, 79,
1920–1923.
7
8
9
reaction. This process involves silylene transfer to a diene
followed by diastereoselective insertion of an aldehyde
into the resultant allylic silane. The highly ordered
transition state of this reaction enables a chiral aldehyde to
discriminate between the enantiomers of the vinyl
silacyclopropane.
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ASSOCIATED CONTENT
Supporting Information. Experimental procedures and
characterization data, including X-ray crystallographic data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Professor Keith Woerpel, Department of Chemistry, New
York University, 100 Washington Square East, New York,
NY 10003 USA
kwoerpel@nyu.edu
Present Addresses
†Department of Chemistry, University of California, Irvine, CA
92697-2025 USA
‡Institut de Recherches Cliniques de Montréal, 110 avenue des
Pins Ouest, Montréal (Québec), H2W 1R7, Canada
ACKNOWLEDGMENT
This research was supported by the National Institute of
General Medical Sciences of the National Institutes of
Health (GM-54909). A Fonds Québécois de la Recherche
sur la Nature et les Technologies fellowship to M. P. is also
acknowledged. We thank Dr. Phil Dennison (UCI) and Dr.
Chin Lin (NYU) for assistance with NMR spectroscopy.
Dr. John Greaves (UCI), Ms. S. Sorooshian (UCI), and Dr.
Lin (NYU) are acknowledged for assistance with mass
spectrometry. We thank Dr. Joe Ziller (UCI) and Dr.
Chunhua Hu (NYU) for X-ray analysis and the Molecular
Design Institute of NYU for purchasing a single crystal
diffractometer.
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Albanov, A. I. Shainyan, B. A. J. Organomet. Chem. 2009, 694,
420–426.
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Table of Contents Graphic
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t-Bu
R1
Si
H
R1
t-Bu
R2
R3
O
Si
R2
AgCO2CF3;
R3CHO
t-Bu
H
t-Bu
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