Regiochemical control in the metal-catalyzed transposition of allylic silyl ethers

Article abstract of DOI:10.1021/ja0620639

A novel mode of regiochemical control over the allylic [1,3]-transposition of silyloxy groups catalyzed by Re2O7 has been developed. This strategy relies on a cis-oriented vinyl boronate, generated from the Alder-ene reaction of homoallylic silyl ethers a

Full text of DOI:10.1021/ja0620639

Published on Web 06/03/2006
Regiochemical Control in the Metal-Catalyzed Transposition of Allylic Silyl
Ethers
Eric C. Hansen and Daesung Lee*
Department of Chemistry, UniVersity of Wisconsin, Madison, Wisconsin 53706
Received April 4, 2006; E-mail: dlee@chem.wisc.edu
Table 1. Protecting Group Effect for Alder-ene Reaction of
Borylated Alkynes-Deprotection-Allylic Transposition
In the context of manipulating synthetic intermediates, the
efficient [1,3]-transposition of allylic heteroatom functionalities is
an important goal in synthetic chemistry.1 One of the most direct
and atom-economical methods for this transformation is a transition-
metal-catalyzed rearrangement of an allylic hydroxyl group.2 Al-
though the rhenium catalyst-based rearrangement developed by Os-
born and co-workers3 is the most efficient method, it generally suf-
fers from low regioselectivity, giving equilibrium mixtures of two
isomers (eq 1). Efforts to control the regioselectivity have focused
on introducing stereoelectronic biasing elements around the allylic
double bond,2c such as conjugation or by taking advantage of the
steric environment of the allylic hydroxyl group.2a,c,4 To further
improve the scope of this rearrangement, we envisioned a new
approach where the equilibrium can be shifted toward the desired
direction by introducing certain functionality within the molecule
that can interact with the [1,3]-transposed hydroxyl group (eq 2).
yield 1
yield 2
yield 3
entry
P
)
(%)
b: deprotection
(%)
(%)d
1
2
3
4
5
CO2Et (a)
Ac (b)
CH2OMe (c)
CO2CH2CCl3 (d)
TBS (e)
68
70
67
33
77
K2CO3/MeOH
LiOH/MeOH
HF/pyr
Zn/AcOH
TBAF
25
30
0e
95
0f
17
20
0
31
0
a With 10 mol % of RuCp(CH3CN)3PF6 at 25 °C. b Deprotection
conditions. c Ph3SiOReO3 or Re2O7 in CH2Cl2, 25 °C. d Three-step yield.
e Protodeboronation was observed. f Decomposition was observed.
protecting group was used. Although the deprotection was nicely
accomplished in Zn/AcOH as expected, the first coupling step gave
low yield of 1d probably due to the ionization of the allylic C-O
bond with the highly activated Troc group.6 A silyl protecting group,
such as TBS (1e), was found to be problematic for its removal in
the presence of the boronate functionality (entry 5).
Having allylic alcohol 2 in hand, we next tried the allylic [1,3]-
transposition. The rearrangement was found to be very efficient to
give an excellent yield of the singly allylic [1,3]-transposed product
in <5 min using either Ph3SiOReO37 or Re2O7 at room temperature.
Surprisingly, the identity of the rearranged product is not the
expected vinyl boronate with the transposed hydroxyl group but
instead the cyclic vinyl boronic acid 3.8 Despite the efficient allylic
transposition, the significance of this overall transformation was
compromised by unacceptably low yields for the three-step sequence
caused by the protecting group incompatibility in the first two steps.
At this juncture, we turned our attention to the possibility of
direct rearrangement of the protected form of hydroxyl functionality.
On the basis of examples of the allylic [1,3]-transposition of silyl
ethers3b,9 in combination with their efficient preparation, we chose
1e as the model substrate for the rearrangement. Gratifyingly,
treatment of 1e with Re2O7 (CH2Cl2, 25 °C, 2 h) provided silyl-
group-free product, which was identical to vinyl boronic acid 3,
the structure of which was confirmed after conversion to 4 via
Suzuki coupling (eq 4).10
In search of a suitable platform that allows us to test this concept,
we became interested in boron’s unique affinity for hydroxyl group.
The cis-vinyl boronate generated from the ruthenium-catalyzed
Alder-ene reaction5 between homoallylic alcohol derivatives and
alkynyl boronates nicely sets the stage for testing the subsequent
allylic [1,3]-transposition, after removal of the hydroxyl protecting
group (eq 3). Herein we report a successful implementation of a
two-step protocol for an efficient synthesis of cyclic vinyl boronic
acids via a novel mode of regiochemical control in the allylic [1,3]-
transposition induced by boronate trapping of hydroxyl and silyloxy
groups.
Having recognized the critical role of the protecting group in
the Alder-ene reaction as well as in the deprotection step,
particularly due to the unstable nature of the boronate both under
basic and acidic conditions, we tested several common protecting
groups on the substrate homoallylic alcohol (Table 1). First, an
ethyl carbonate and an acetate group were used (entries 1 and 2),
which gave a good yield of the Alder-ene reaction products 1a and
1b, respectively. However, deprotection of these protecting groups
under typical mildly basic conditions gave only low yield of free
alcohol 2. Again, ethereal protecting group MOM is suitable for
the first step, but its removal under acidic conditions led to rapid
protodeboronation (entry 3). To avoid both basic and acidic aqueous
conditions for the deprotection, the Troc (trichloroethyloxycarbonyl)
Encouraged by this observation, a variety of cis-vinyl boronates
were synthesized via the Alder-ene reaction in order to test the
generality of the rearrangement (Table 2). Substrates 5a-d were
obtained in good yield and moderate selectivity for the Z-isomer.11
Under typical conditions (Re2O7; CH2Cl2 or Et2O, 25 °C), these
substrates provided the rearrangement products 6a-d in excellent
yields.12 Unexpectedly, products 5e and 5f were not obtained from
9
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J. AM. CHEM. SOC. 2006, 128, 8142-8143
10.1021/ja0620639 CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Suzuki Coupling of Cyclic Vinyl Boronic Acids
Table 2. Allylic [1,3]-Transposition of Silyl Ethers
regiochemical control in the allylic [1,3]-transposition was achieved
by using the oxygen affinity of a cis-oriented vinyl boronate to
trap out the hydroxyl and silyloxy group. Application of this
consecutive Alder-ene reaction followed by allylic transposition to
natural products synthesis is underway.
Acknowledgment. We thank NIH (CA106673) for financial
support of this work as well as the NSF and NIH for NMR and
mass spectrometry instrumentation. E.C.H. thanks Abbott Labo-
ratories for an Abbott fellowship. D.L. is a fellow of the Alfred P.
Sloan Foundation.
Supporting Information Available: General procedures and
characterization of represented compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
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a With 5 mol % of RuCp(CH3CN)3PF6 in acetone at 25 °C. b With 2.5
mol % of Re2O7 in CH2Cl2 or ether at 25 °C. c Mixtures of boronate
stereoisomers. d Based on recovered starting material. e Racemic mixture.
Table 3. Chirality Transfer for Allylic [1,3]-Transposition
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the Alder-ene reaction. Instead, the reaction directly lead to the
[1,3]-transposed products 6e and 6f in 43 and 54% yields,
respectively (entries 5 and 6).10,13 This tandem Alder-ene reaction
followed by allylic transposition is probably due to the activated
nature of the benzylic silyl ether toward the cationic ruthenium
catalyst employed.6
The rearrangement of 5d renders the important issue of chirality
transfer during the reaction (entry 4). Because the assessment of
the diastereomeric ratio of 6d14 was not trivial, enantioenriched
substrates 5b and 5c were tested. Interestingly, when the rearrange-
ment was performed in CH2Cl2, significant loss of stereochemical
information was observed for 6b and 6c (Table 3). However, when
the reaction was run in ether, the stereochemical integrity was
preserved.15 The efficiency of chirality transfer from 5b to 6b and
5c to 6c was determined by analysis of the Mosher ester derivatives
after conversion to 7b and 7c.
(7) The more soluble catalyst, Ph3SiOReO3, gave lower conversion in the
current reaction. For synthesis and structure of this catalyst, see: Schoop,
T.; Roesky, H. W.; Noltemeyer, M.; Schmidt, H.-G. Organometallics 1993,
12, 571-574.
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S. K.; Srinivas, D. J. Org. Chem. 2001, 66, 7148-7150. (b) Micalizio,
G. C.; Schreiber, S. L. Angew. Chem., Int. Ed. 2002, 41, 3272-3276. (c)
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M. R. Inorg. Chem. 1997, 36, 465-471.
(10) The cyclic boronic acids could be identified by crude 1H NMR, but
complete characterization was only achieved after derivitization via Suzuki
coupling.
(11) Higher Z/E ratios had been observed previously for alkenes with no
branching substituents in the homoallylic position (ref 5).
(12) The E-isomer could be recovered as a mixture of allylic silyl ether
regioisomers.
(13) Complete racemization of 6e was observed.
(14) 6d represents the C4-C16 subunit of (-)-zampanolide and (-)-dacty-
lolide. Details of its use in total synthesis will be reported in a future
article.
The cyclic vinyl boronic acids 6a-f were found to be excellent
coupling partners in Suzuki couplings.14,16 Compounds 6a-c and
6e,f underwent coupling with cis-ethyl-â-iodoacrylate to give the
corresponding coupled products 7a-c and 7e,f, representative
examples of which are illustrated in Scheme 1.
(15) Chirality transfer has been observed for cyclic allylic alcohols. See: Troste,
B. M.; Toste, F. D. J. Am. Chem. Soc. 2000, 122, 11262-11263. Acyclic
allylic alcohols require low temperatures (-78 °C) for chirality transfer
(ref 4).
(16) (a) Frank, S. A.; Chen, H.; Kunz, R. K.; Schnaderbeck, M. J.; Roush, W.
R. Org. Lett. 2000, 2, 2691-2694. (b) For a review, see: Miyaura, N.;
Suzuki, A. Chem. ReV. 1995, 95, 2457-2483.
In conclusion, we have developed a highly efficient protocol for
the synthesis of cyclic vinyl boronic acid. This novel mode of
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