Silylene-mediated polarity reversal of dienoates: Additions of dienoates to aldehydes at the δ-position to form trans-dioxasilacyclononenes

Article abstract of DOI:10.1021/ja109631z

Silylene transfer to αβ,γ,δ-unsaturated carbonyl compounds produced oxasilacyclopentenes that underwent thermal additions to aldehydes to produce trans-dioxasilacyclononenes as single stereoisomers. This reaction, which converts the δ-position of the unsa

Full text of DOI:10.1021/ja109631z

Published on Web 12/17/2010
Silylene-Mediated Polarity Reversal of Dienoates: Additions of Dienoates to
Aldehydes at the δ-Position To Form trans-Dioxasilacyclononenes
Christian C. Ventocilla and K. A. Woerpel*
Department of Chemistry, UniVersity of California, IrVine, California 92697-2025, United States, and
Department of Chemistry, New York UniVersity, New York, New York 10003, United States
Received October 26, 2010; E-mail: kwoerpel@nyu.edu
The anti configuration of the addition product 4 is likely
Abstract: Silylene transfer to R,ꢀ,γ,δ-unsaturated carbonyl com-
established through a Zimmerman-Traxler-like10 transition state
pounds produced oxasilacyclopentenes that underwent thermal
additions to aldehydes to produce trans-dioxasilacyclononenes
center (A, Figure 1). Although E-allylic silanes typically react with
in which the aldehyde is activated by coordination to the silicon
as single stereoisomers. This reaction, which converts the
δ-position of the unsaturated carbonyl compound into a nucleo-
philic center, represents an inversion of polarity from the normal
pattern of reactivity. The stereospecificity of the reaction suggests
that the addition to aldehydes occurred through a closed, chairlike
six-membered transition state. This reaction can be used to
prepare enantiomerically pure materials by the use of chiral
auxiliaries to control the formation of the oxasilacyclopentenes.
Figure 1
Functionalization of the resulting trans-cycloalkene occurred with
complete stereoselectively.
aldehydes in the presence of Lewis acids through open transition
states to give syn products,11,12 allylic silanes can react through
closed transition states if the silicon atom is particularly Lewis
The different positions of unsaturated carbonyl compounds exhibit
acidic.8,13 Three facts support the closed transition state for the
predictable patterns of reactivity. While the R- and γ-positions are
formation of adduct 4: (1) an external Lewis acid was not required
donor sites, the ꢀ- and δ-positions are acceptors.1 For example, the
to activate the addition of silane 3 to an aldehyde; (2) the E-allylic
aldol reaction, in which the R-position is nucleophilic, is a common
silane gave the anti product, not the syn product; and (3) no
transformation,2 and the vinylogous aldol reaction uses the γ-position
Mukaiyama14 R-aldol products were formed by reaction of the more
as a nucleophile.3 Conjugate addition reactions capitalize on the
nucleophilic silyl ketene acetal moiety.15
electrophilicity of the ꢀ- and δ-positions.4 The polarity of these
The stereospecificity of the addition reaction also indicates that
positions can be reversed in some cases. For example, formal
it proceeds through a closed transition state.16 The product obtained
homoaldol reactions employ the ꢀ-position as a nucleophilic site.5
from the Z-dienoate 6 was the syn isomer of the trans-dioxasila-
Umpolung reactivity where the δ-position is nucleophilic, on the other
cyclononene (7, eq 2).9 The relative configuration of trans-
hand, is uncommon.6
dioxasilacyclononene 7 is also consistent with its formation through
In this communication, we present a method for addition of
a closed, chairlike transition state.11,12
aldehydes to dienoates at the δ-carbon. Silylene transfer to a
dienoate forms a vinyl oxasilacyclopentene in which the δ-carbon
becomes the nucleophilic site. These intermediates undergo nu-
cleophilic additions to aldehydes, forming trans-dioxasilacy-
clononenes stereoselectively and stereospecifically.
The one-flask conversion of dienoate 1 and benzaldehyde to the
protected adduct 5 illustrates this transformation. Silver-catalyzed
silylene transfer7 to dienoate 1 afforded vinyl oxasilacyclopentene 3
The trans-cyclononene products can be formed with control
cleanly. Heating strained8 vinyl oxasilacyclopentene 3 with benzal-
of absolute stereochemistry. The chiral auxiliary of dienimide
8 controlled the silylene transfer reaction, resulting in stereo-
selective formation of intermediate 9 (Scheme 1). Heating this
silane with benzaldehyde promoted the diastereoselective forma-
tion of trans-dioxasilacyclononadiene 10.17 Treatment of diene
10 with acid under biphasic conditions removed the chiral
auxiliary, providing enantioenriched trans-dioxasilacyclononene
(-)-5.
dehyde produced the dienol ether 4 as a single diastereomer. Filtration
through silica gel hydrolyzed the silyl ketene acetal to provide the
corresponding trans-dioxasilacyclononene 5 as one diastereomer.9
The addition of aldehydes at the δ-position of dienoates is
general for a number of unsaturated esters (eq 3). Reaction times,
however, depend upon the nucleophilicity of the allylic silane
formed after silylene transfer. Substrates that possessed a methyl
substituent at the γ-position (Table 1, entries 1, 2, and 4)
produced methallyl silanes that underwent faster addition relative
to substrates that only had a hydrogen atom at that position.15
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406 J. AM. CHEM. SOC. 2011, 133, 406–408
10.1021/ja109631z  2011 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Asymmetric Formation of trans-Dioxasilacyclononene
formed by the Lewis acid catalyzed process was again consistent
with a closed, chairlike transition state. The Lewis acid likely
coordinated to the oxygen atom of the O-Si bond of the vinyl
oxasilacyclopentene 3, increasing the electrophilicity of the
silicon center.18
Stereochemically homogeneous products can be made by kinetic
resolution. Addition to a chiral aldehyde (Table 2, entry 4) produced
the adduct as a single diastereomer.17 The relative stereochemistry
of trans-dioxasilacyclononene 21 is consistent with a closed,
chairlike transition state where the vinyl oxasilacyclopentene
approached the chiral aldehyde on a Felkin trajectory.19 This result
suggests that the use of chiral, nonracemic aldehydes would give
enantioenriched products.
Because substituted trans-cyclononenes adopt specific conforma-
tions and are slow to isomerize,20 functionalization of the
carbon-carbon double bond only occurred on the outside face.
Treatment of trans-dioxasilacyclononene 21 with m-CPBA followed
by deprotection afforded epoxide 23 as a single diastereomer. This
selectivity is noteworthy because epoxidations of acyclic alkenes
with m-CPBA in which the faces of the alkene are only differenti-
ated by A1,2 strain are generally not diastereoselective.21 In addition,
hydroxyl-directed epoxidation of free alcohols with structures
analogous to cyclononene 21 would give epoxides with the opposite
relative configuration compared to epoxide 23.21
The longer reaction times of the substrates that only had a
hydrogen atom at the γ-position led to more decomposition
products and lower yields.
Table 1. Dienoate Scope in Formation of
trans-Dioxasilacyclononenes (eq 3)a
entry
Dienoate
R1
R2
R3
Conditions
Product
Yield
1
2
3
4
5
6
1
6
11
12
13
14
H
Me
H
H
Me
H
Me
H
Me
H
Me
H
Me
Me
H
Me
H
100 °C, 18 h
100 °C, 18 h
100 °C, 5 d
100 °C, 2 d
100 °C, 10 d
100 °C, 5 d
5
7
15
16
17
18
77%
67%
59%
53%
38%
37%
In summary, silylene transfer to dienoates afforded intermedi-
ates that function as δ-enolate equivalents that react with
aldehydes to form addition products stereoselectively and
stereospecifically. Enantiopure products can be synthesized by
employing a chiral auxiliary to control silylene transfer. Further
functionalization of the trans-cycloalkene occurred diastereo-
selectively. This methodology has potential application for the
synthesis of polypropionate natural products and related struc-
tures.22
H
a Products were formed as one isomer as determined by 1H NMR
spectroscopy and GCMS. Yields reported are isolated yields.
A number of aldehydes participated in the addition reaction
(eq 4). Reactions of sterically hindered aldehydes required longer
reaction times (Table 2, entries 3 and 4). A Lewis acid catalyzed
the allylation, leading to faster reactions, even at room temper-
ature (entry 4). The relative stereochemistry of the products
Acknowledgment. This project was supported by the National
Institute of General Medical Sciences of the National Institutes of
Health (GM-54909). C.C.V. thanks the NIGMS for a predoctoral
fellowship (F31GM080157). K.A.W. thanks Amgen and Lilly for
awards to support research. We thank Dr. Phil Dennison (UCI) for
assistance with NMR spectroscopy, Dr. Joseph W. Ziller (UCI)
for X-ray crystallography, and Dr. John Greaves and Ms. Shirin
Sorooshian (UCI) for mass spectrometry.
Table 2. Aldehyde Scope (eq 4)a
Supporting Information Available: Experimental procedures;
spectroscopic, analytical, and X-ray data for the products (PDF,CIF).
This information is available free of charge via the Internet at http://
pubs.acs.org.
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