Nickel-catalyzed preparation of stereodefined allylic alcohols using silicon-tethered ynals

Article abstract of DOI:10.1016/S0040-4039(01)00461-0

The nickel-catalyzed cyclization of silicon-tethered ynals is reported. The silicon heterocycles obtained may be converted into allylic alcohols that possess a stereodefined alkene unit via a cleavage process that involves stereospecific protodesilylation of the vinyl silane functionality.

Full text of DOI:10.1016/S0040-4039(01)00461-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3259–3261
Nickel-catalyzed preparation of stereodefined allylic alcohols
using silicon-tethered ynals
Mario Lozanov and John Montgomery*
Department of Chemistry, Wayne State University, Detroit, MI 48202-3489, USA
Received 28 February 2001; accepted 19 March 2001
Abstract—The nickel-catalyzed cyclization of silicon-tethered ynals is reported. The silicon heterocycles obtained may be
converted into allylic alcohols that possess a stereodefined alkene unit via a cleavage process that involves stereospecific
protodesilylation of the vinyl silane functionality. © 2001 Published by Elsevier Science Ltd.
Achiral allylic alcohols and their derivatives are ver-
satile substrates in a variety of asymmetric transforma-
tions including Claisen rearrangements and related
processes,1 epoxidations,2 cyclopropanations,3 and pal-
ladium-catalyzed allylic substitutions (Scheme 1).4
Despite the impressive utility of these processes, many
classes of the requisite allylic alcohols that possess tri-
or tetra-substituted alkenes are quite difficult to prepare
in an isomerically-pure fashion. Our group has recently
reported a method for the preparation of cyclic and
acyclic allylic alcohols by nickel-catalyzed cyclizations
or couplings of an aldehyde and an alkyne.5 Given the
broad utility of allylic alcohols in the asymmetric pro-
cesses cited above, we became interested in applying the
nickel-catalyzed ynal cyclization in the preparation of
achiral allylic alcohols with a high degree of substitu-
tion about the alkene moiety. The products obtained
would thus be attractive precursors for many asymmet-
ric processes.
The most direct entry to achiral allylic alcohols by the
nickel catalysis strategy would involve couplings of
alkynes with formaldehyde. Reactions with formalde-
hyde, however, were much less efficient than the corre-
sponding reactions with aliphatic and aromatic
aldehydes. Furthermore, regioselectivities of the alkyne
insertion were poor for most substrates. In order to
circumvent these limitations, we have examined the
temporary silicon-connection method in ynal cycliza-
tions (Scheme 2).6 This approach enjoys the entropic
advantages of the intramolecular variant and generates
adducts which may be oxidatively-degraded into the
products that would be obtained by formaldehyde cou-
plings. As demonstrated in this study, the cyclic vinylsi-
sigmatropic
rearrangements
cyclopropanation
R2
HO
R1
R3
Pd-π-allyl
chemistry
epoxidation
Scheme 1. Allylic alcohols in asymmetric synthesis.
R2
R2
R1
O
R1
HO
O
HO
R1
R3(H)
H
Si
Ph
Ph
Si
Ph
Ph
O
Scheme 2. Strategy for preparation of allylic alcohols.
Keywords: nickel; silicon heterocycles; alkenes.
* Corresponding author. Fax: (313) 577-1377; e-mail: jwm@chem.wayne.edu
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00461-0

3260
M. Lozano6, J. Montgomery / Tetrahedron Letters 42 (2001) 3259–3261
lanes may be cleaved by protodesilylation to afford allylic
alcohols with a stereodefined trisubstituted alkene.7 Fur-
thermore, electrophilic functionalization of the vinylsi-
lane moiety may ultimately provide access to allylic
alcohols that possess a stereodefined tetrasubstituted
alkene.8
For purposes of obtaining allylic alcohols with a trisub-
stituted alkene moiety, the most direct and efficient
procedure involves treatment of the crude reaction mix-
ture from a nickel-catalyzed cyclization with nBu4NF to
afford the 1,2-diol with concomitant protodesilylation of
the vinyl silane in a single step (Scheme 4).11 Treatment
of the diol with periodic acid in ether cleanly afforded
the expected aldehyde which was directly treated with
NaBH4/CeCl3 to afford the desired allylic alcohols 6a–f
in >95:5 isomeric purity. The examples shown demon-
strate that aromatic and aliphatic alkynes as well as
conjugated enynes participate in the new coupling reac-
tion. Furthermore, aromatic and aliphatic organozincs
are tolerated in the cyclization. The formation of com-
pounds 6e and 6f demonstrates high selectivity that
would undoubtedly be difficult to achieve with methods
that involve carbonyl olefination.
The requisite silicon-tethered ynals were most effectively
prepared by initial addition of a lithium acetylide to
dimethyldichlorosilane to afford chloroalkynylsilanes
1a–d.9 Chlorosilanes 1a–d and hydroxyaldehyde 2 were
then stirred in CH2Cl2 at 0°C with Et3N and catalytic
DMAP for 15 min to directly afford ynals 3a–d (Scheme
3). The gem–diphenyl moiety was chosen simply because
of the stability and ease of preparation of hydroxyalde-
hyde 2,10 and we expect that other linkages would be
equally effective in the subsequent cyclization processes.
With the desired ynals in hand, we examined the
efficiency of nickel-catalyzed cyclizations with organo-
zincs according to procedures previously developed in
our labs.5 Organozincs were prepared by treatment of
anhydrous zinc chloride in THF with an organolithium
or organomagnesium reagent (1.6:1 stoichiometry). A
mixture of the organozinc with Ni(COD)2 (10 mol%) was
transferred to a THF solution of the ynal and trimethylsi-
lyl chloride. After 1 h at 0°C, trimethylsilyl-protected
silicon heterocycles 4a–f were efficiently formed (Scheme
4). Treatment with HF·pyridine selectively deprotected
the trimethylsilyl moiety to afford alcohol derivatives
5a–f, whereas treatment with nBu4NF resulted in exhaus-
tive silyl cleavage to afford the corresponding acyclic
diols. In the nBu4NF-mediated process, protodesilyla-
tion proceeded cleanly to afford the trisubstituted alkene
in a stereospecific fashion.7
In summary, a new method for preparing highly substi-
tuted allylic alcohols utilizing temporarily-tethered ynals
was developed. Significantly, a high degree of selectivity
in the formation of trisubstituted alkenes was observed,
thus avoiding the need for tedious separation of alkene
stereoisomers. Further investigation of the utility of the
silicon heterocycles obtained is in progress.
Acknowledgements
Acknowledgement is made to the NIH (R01 GM57014)
and to the Dreyfus Foundation (Camille Dreyfus
Teacher Scholar Award to J.M.) for their support of this
research.
O
R1
OH
3a, R1 = n-hexyl (71 %)
R1
O
H
Cl
3b, R1 = Ph (62 %)
Ph Ph
O
Si
H
Si
3c, R1 = C(CH3)=CH2 (65 %)
3d, R1 = p-tolyl (60 %)
2
Ph
Ph
1a-d
(reference 9)
Et3N, DMAP
Scheme 3. Cyclization of silicon-tethered ynals.
R2Li / ZnCl2
R1
O
or R2MgBr / ZnCl2
O
H
Si
TMSCl
Ni(COD)2 (10 mol %)
Ph
R1
yield from 3
R2
product
Ph
3a-d
6a
6b
6c
6d
6e
6f
63 %
60 %
61 %
58 %
29 %
27 %
Ph
hexyl
Me
R2
Ph
1) nBu4NF
R2
Me
Me
p-tolyl
Ph
hexyl
R3O
R1
2) H5IO6
C(CH3)=CH2
Ph
3) NaBH4, CeCl3
HO
R1
Ph
Si
p-tolyl
H
O
Ph
6a-f
4, R3 = TMS
5, R3 = H
>95:5 E/Z selectivity
HF·pyr
Scheme 4. Silicon heterocycle formation and oxidative cleavage.

M. Lozano6, J. Montgomery / Tetrahedron Letters 42 (2001) 3259–3261
3261
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