Diastereoselective synthesis of eight-membered-ring allenes from propargylic epoxides and aldehydes by silylene insertion into carbon-oxygen bonds

Article abstract of DOI:10.1002/anie.201306093

Bent out of shape: Silver-catalyzed insertions of silylenes into propargylic C - O bonds of epoxides regioselectively form 1,2-silaoxetanes, which add to aldehydes to give the title allenes as single diastereomers (see scheme; Ts=4-toluenesulfonyl). An X-ray crystal structure confirmed the stereochemistry of the allene, which is bent significantly from linearity (164°). Copyright

Full text of DOI:10.1002/anie.201306093

Angewandte
Chemie
DOI: 10.1002/anie.201306093
Medium-Ring Compounds
Diastereoselective Synthesis of Eight-Membered-Ring Allenes from
Propargylic Epoxides and Aldehydes by Silylene Insertion into
Carbon–Oxygen Bonds**
Christina Z. Rotsides, Chunhua Hu, and K. A. Woerpel*
The synthesis of eight-membered-ring allenes is limited by the
difficulty of constraining cumulated double bonds within
a medium-sized ring. Forcing the allene functionality into
a medium-sized ring puts significant strain on the ring and
distorts the allene from its optimal bond and torsional
angles.[1] As a result, eight-membered-ring allenes are either
reactive intermediates[2,3] or require bulky substituents to
stabilize them.[4,5] Introducing elements with longer atomic
radii such as sulfur, selenium, phosphorus, or silicon reduces
the ring strain of cyclic allenes sufficiently in some cases to
permit isolation.[6–9] For example, six-, seven-, and eight-
membered-ring allenes containing three silicon atoms have
been isolated.[10–12] Most cyclic allenes contain carbon–hetero-
Scheme 1. Insertion of a silylene into a propargylic carbon–oxygen
atom bonds directly on the allene, which impart stability by
polarizing the allene functionality to favor charge-separated
resonance forms.[13] For example, four- and five-membered-
ring allenes have been reported that rely on p-donor
substituents to stabilize the highly distorted allene functional
group.[14,15]
bond and subsequent aldehyde addition. TBS=tert-butyldimethylsilyl,
Ts =4-toluenesulfonyl.
Herein, we report the two-step, one-flask diastereoselec-
tive synthesis of eight-membered-ring allenes. An X-ray
crystal structure revealed significant deviations from the
optimal bond and torsional angles as compared to uncon-
strained allenes.[16] Deprotection of these cyclic allenes
provided tetrasubstituted allenes with control of the relative
configurations between the carbon stereocenter and the axis
of chirality.[17,18]
The synthesis of eight-membered-ring allenes relies on the
unique reactivity of silylenes and strained cyclic silanes.
Treatment of the epoxide 1a with a catalytic amount of
a silver salt at À208C for three hours provided the silaoxetane
3a (Scheme 1). The uncatalyzed[19] addition of an aldehyde to
this strained propargylic silane formed the eight-membered-
ring allene as a single diastereomer (Scheme 1). When the
epoxide 1b was used, a similar allene was obtained [Eq. (1)].
The trisubstituted allenes 4a and 4b, however, were not stable
to isolation: they were so reactive that they decomposed
readily even when stored under a nitrogen atmosphere.
By contrast, tetrasubstituted allenes derived from more
substituted propargylic epoxides were isolable and stable to
silica gel chromatography. This reaction sequence was general
for a variety of propargylic epoxides (Table 1) and aldehydes
(Table 2), thus yielding tetrasubstituted allenes as single
diastereomers. The epoxide 5c provided the allene 6c in
lower yield, probably because of steric congestion at the atom
undergoing insertion. The yield of 7d is lower than those of
the other allenes because of the difficulty with purification,
Table 1: Formation of eight-membered-ring cyclic allenes.
[*] C. Z. Rotsides, Dr. C. Hu, Prof. K. A. Woerpel
Department of Chemistry, New York University
100 Washington Square East, New York, NY 10003 (USA)
E-mail: kwoerpel@nyu.edu
Entry
R1
R2
6
Yield [%][a]
1
2
3
4
Me
Me
iPr
C6H13
CH2CH2OTBS
C6H13
6a
6b
6c
6d
71
58
35
66
[**] The authors thank New York University and the Margaret and
Herman Sokol Fellowship (to C.Z.R.) for support of this research.
We thank the NYU Molecular Design Institute for the purchase of
the Bruker SMART APEXII diffractometer.
Me
SiMe3
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201306093.
[a] Yield of isolated product from reaction run on a preparative scale
(1 mmol).
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Table 2: Aldehyde scope for allene synthesis.
Entry
RCHO
7
Yield [%][a]
1
2
7a
7b
60
54
3
7c
49
4
5
7d
7e
21
53
iPr
Figure 1. Molecular structure of 8 (ellipsoids set at 50% probability).
Hydrogen atoms on the phenyl ring and tert-butyl groups are emitted
for clarity. Selected bond lengths [ꢀ] and angles [8]: C2–C3 1.300(7),
C3–C4 1.321(8), O1–Si1 1.648(4), O2–Si1 1.637(4); C2-C3-C4 164.0(6),
O1-Si1-O2 116.7(2).[38]
[a] Yield of product isolated from reaction run on a preparative scale
(1 mmol).
thus suggesting that this crotonaldehyde-derived allene is
more reactive. The observation that only tetrasubstituted
allenes could be isolated and purified demonstrates that the
allene is strained, thus requiring steric hinderance to prevent
undesired decomposition reactions.[4,20]
torsion angles around the allene is 81.68, as compared to 908,
thus indicating that the ends of the allene are not perpendic-
ular to each other.[25]
These cyclic allenes could be deprotected to provide
either homoallylic alcohols or linear allene diols depending
on reaction conditions. The allene 6b containing a primary
silyl ether could be selectively deprotected to provide the
allene 8 [Eq. (2)]. More forcing conditions were required to
remove the di-tert-butylsilyl group [Eq. (3)]. When the allenes
Because the strained allene is not stabilized by a hetero-
atom substituent, the bond angle and torsional angle dis-
tortions are not likely the result of electronic effects.
Heteroatoms in other cyclic allenes stabilize the cumulated
bonds by donating electron density into the allene antibond-
ing p* orbitals, thus leading to charge-separated resonance
forms.[13] This electronic interaction results in twisting of the
ends of an allene towards a coplanar orientation and length-
ening of the allene carbon–carbon bonds. In one example,
a five-membered ring allene with four heteroatom substitu-
ents has coplanar allene substituents, and the allene carbon–
carbon bond lengths are dramatically lengthened (1.370 and
1.386 ꢀ).[14] By contrast, a seven-membered-ring allene with
one silicon atom connected to the allene is twisted by 308, but
the allene carbon–carbon bond lengths are closer to their
unconstrained values (1.307 and 1.293 ꢀ compared to
1.31 ꢀ).[12] Because the bond distances in 8 do not deviate
considerably from the optimal bond length for allenes
(1.31 ꢀ)[26] and the allene is not highly twisted, the deviations
from optimal bond angle and torsional angles in 8 most likely
result from strain induced by the ring.[17]
6a and 7a were heated with a solution of nBu4NF that had
been dried over 3 ꢀ molecular sieves, the di-tert-butylsilyl
group was removed. In contrast, the allene was not compat-
ible with standard acidic conditions for deprotection.[21]
X-ray crystallography revealed significant deviations of
both the bond and torsion angles of the allene, thus indicating
Experiments with substituted propargylic epoxides
revealed that carbon–carbon bond formation is stereospecific,
but silylene transfer is not. Silylene transfer to the diastereo-
meric propargyl epoxides 11a and 11b provided diastereo-
meric silaoxetanes, although some erosion of stereochemistry
occurred (Table 3).[27] Upon addition of benzaldehyde, dia-
stereomeric allenes were formed with product ratios matching
those of the silaoxetane mixtures.[28] Similar observations
were made when the epoxide 11c was employed.
The loss of stereochemistry during insertion of the silylene
(Table 3) into the carbon–oxygen bond suggests that insertion
proceeds through a ring-opened intermediate such as dirad-
ical B (Scheme 2).[29,30] After coordination of a silver silylene
that these allenes are strained (Figure 1).[22] The C2-C3-C4
bond angle is bent from linearity by 168.[23] Comparison of
other bond angles in similar eight-membered-ring systems
reveals that this 1648 bond angle is among the smallest bond
angles reported for cyclic allenes.[24] The average of the
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Table 3: Synthesis of diastereomeric allenes.
transition state for aldehyde addition (Figure 2). Coordina-
tion of the carbonyl group to the Lewis-acidic silicon atom[37]
of the strained four-membered-ring silane forms the adduct C
Entry
11
R1
R2
R3
%
d.r.[c]
1
2
3
11a
11b
11c
Me
H
H
H
Me
H
H
H
Me
49[a]
46[b]
32[b]
71:29 (71:29)
37:63 (33:67)
73:27 (70:30)
1
[a] Yield determined by H NMR spectroscopy using mesitylene as an
internal standard. [b] Yield of product isolated after removal of the TBS
group. [c] Determined using 1H NMR spectroscopy. Values within
parentheses are for the silaoxetane intermediates.
Figure 2. Transition state for aldehyde addition.
intermediate to the epoxide oxygen atom (intermediate A),
homolytic cleavage of the propargylic carbon–oxygen bond
would afford the intermediate B. If carbon–carbon bond
rotation were competitive with radical ring closure, then
in which the aldehyde is activated for carbon–carbon bond
formation.[27] This pentacoordinate silicon atom adopts
a geometry in which the tert-butyl groups are placed in
basal positions to avoid steric interactions with each
other.[27,36] The cyclic transition-state D accounts for how
the point chirality of the starting material is translated to both
the point chirality and axial chirality of the product.
In conclusion, allenes embedded within the constraints of
an eight-membered ring can be synthesized as single diaste-
reomers by inserting a silylene into a propargylic carbon–
oxygen bond followed by aldehyde addition. These tetrasub-
stituted cyclic allenes are stable to ambient conditions and do
not require any special handling. Examination of the X-ray
crystal structure revealed that the allene is bent significantly
from linearity by the strain caused by incorporation of this
functional group into a medium-sized ring.
Received: July 12, 2013
Published online: October 9, 2013
Scheme 2. Insertions of silylenes into propargylic carbon–oxygen
bonds.
Keywords: allenes · medium-ring compounds ·
reactive intermediates · silicon · strained molecules
.
scrambling of stereochemistry would be expected.[31,32] Stabi-
lization of a radical by an adjacent alkynyl group supports this
mechanism and explains the observed regioselectivity of
silaoxetane formation.[33]
Insertions of silylenes into carbon–oxygen bonds do not
require release of ring strain from an epoxide.[34,35] Silylene
transfer to the acylic propargyl ethers 14a,b provided
propargyl silanes 15a,b as single regioisomers [Eq. (4)]. The
allenes 16a,b, which would result from transposition of the
p bond, were not observed. By contrast, insertions of silylenes
into allylic carbon–oxygen bonds are accompanied by allylic
transposition.[27,31,32,36]
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