Diastereoselective intramolecular cycloaddition of vinylsilanes and silyl nitronates. Effective control of remote acyclic asymmetry

Full text of DOI:10.1021/jo982180p

692
J . Org. Chem. 1999, 64, 692-693
Sch em e 1
Dia ster eoselective In tr a m olecu la r
Cycloa d d ition of Vin ylsila n es a n d Silyl
Nitr on a tes. Effective Con tr ol of Rem ote
Acyclic Asym m etr y
David G. J . Young,1 Enrique Gomez-Bengoa, and
Amir H. Hoveyda*
Department of Chemistry, Merkert Chemistry Center,
Boston College, Chestnut Hill, Massachusetts 02467
Received October 30, 1998
A number of research groups have reported protocols
through which Si tethers can be used to promote regio- and
stereoselective transformations.2 Related work from these
laboratories has focused on the synthetic applications of
chiral siloxanes,3 obtained from diastereoselective Pt-
catalyzed intramolecular hydrosilation.4 Herein, we report
on the intramolecular cycloaddition of vinyl silanes and silyl
nitronates; in these transformations, high levels of diaste-
reocontrol are effectively induced by a stereogenic carbon
center that bears a Si substituent.
Sch em e 2a
The present studies arose in the context of a total
synthesis effort that required the stereoselective preparation
of a fragment represented by I (Scheme 1). Specifically, we
were interested in devising an efficient protocol for the
control of the C1-C4 relative stereochemistry. One proposed
plan involved the use of an intermediate vinylsilane (V),
which would be converted to the corresponding nitronate
IV.5 A subsequent stereoselective [3 + 2] cycloaddition,6
followed by silyloxide elimination, would deliver II. Reduc-
tive cleavage of II was envisioned to allow access to I. The
requisite vinylsilane would be accessed through alkylation
of the corresponding siloxanes VI, which would be prepared
stereoselectively by Pt-catalyzed intramolecular hydrosila-
tion.
To examine the feasibility of this approach, we prepared
2 by the Pt-catalyzed intramolecular hydrosilation of the
siloxy hydride derived from 1 (Scheme 2). Subjection of 2 to
1.5 equiv of vinylmagnesium bromide resulted in the opening
of the siloxane ring; subsequent conversion of the primary
carbinol to nitro adduct 3 proceeded as illustrated in Scheme
2. Treatment of vinylsilane 3 with 2 equiv of TMSCl and
Et3N at 22 °C (CH2Cl2) for 12 h afforded bicyclic isoxazoline
5, presumably via isooxazolidine 4, in 90% isolated yield as
a 4.5:1 mixture of stereoisomers.7
a
Key: (a) 1.5 equiv of 1,1,3,3-tetramethyldisilazane, 0.1 mol % Pt-
divinylsiloxane, 22 °C, CH2Cl2; (b) 1.5 equiv of H2CdC(H)MgBr, -78
f 0 °C, 6 h, THF; 67% from 1; (c) 1.1 equiv of TsCl, 1.1 equiv of Et3N,
0.1 equiv of DMAP, 22 °C, CH2Cl2, 12 h; 71%; (d) 5 equiv of LiI, 65 °C,
THF, 7 h; 79%; (e) 1.7 equiv of H2NCONH2, 2.1 equiv of NaNO2; DMF,
36 h, 35%; (f) 2 equiv of TMSCl, 2 equiv of Et3N, 22 °C, 12 h, CH2Cl2;
90%.
moderate levels of diastereoselectivity (6 f 7; 7:1). As
illustrated in entry 2, when the vinyl unit is disubstituted,
isoxazoline formation occurs efficiently (72%) but also with
1
excellent stereocontrol (>20:1, 400 MHz H NMR). Diaste-
reoselective cycloadditions in entries 3-4 involve more
highly functionalized substrates. The latter two reactions
indicate that (a) both cis- and trans-vinylsilanes react
selectively to afford the corresponding heterobicycles with
complete relay of stereochemistry and (b) depending on the
stereochemical identity of the substrate, in situ protodesi-
lation8 may occur to afford the derived heterocycle (10 f
11 vs 12 f 13). This difference in stability is likely due to
the steric strain caused by the Me unit in the initial
cycloadduct obtained from 10 (Me group is oriented toward
the concave face of the cycloadduct); rupture of the C-Si
bond leads to the relief of steric strain.
The transformation depicted in entry 1 of Table 1 is
another illustration of the intramolecular cycloaddition with
a vinylsilane: the reaction proceeds in 81% yield but with
Transformations involving terminal vinyl silanes illus-
trated in entries 5 and 6 of Table 1 highlight two additional
attributes of the present method: (a) In contrast to the
reactions involving the less substituted 3 and 6, transforma-
tions with the more functionalized 14 and 16 proceed with
outstanding levels of stereochemical control. (b) Whereas
reactions with silyl nitronates occur stereoselectively, the
derived nitrile oxides9 (condition B; formed by dehydration
of the substrate with phenyl isocyanate) undergo cycload-
dition with significantly lower levels of diastereoselection.
(1) Present address: Department of Chemistry, University of Tennessee,
Knoxville, TN 37996.
(2) For recent reviews on the utility of Si-containing compounds in
synthesis, see: (a) Bols, M.; Skrydstrup, T. Chem. Rev. 1995, 95, 1253-
1277. (b) Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063-
2192.
(3) (a) Hale, M. R.; Hoveyda, A. H. J . Org. Chem. 1992, 57, 1643-1645.
(b) Hale, M. R.; Hoveyda, A. H. J . Org. Chem. 1994, 59, 4370-4374. (c)
Young, D. G. J .; Hale, M. R.; Hoveyda, A. H. Tetrahedron Lett. 1996, 37,
827-830.
(4) Tamao, K.; Nakajima, T.; Sumiya, R.; Arai, H.; Higuchi, N.; Ito, Y. J .
Am. Chem. Soc. 1986, 108, 6090-6093.
(5) For a recent application of silylnitronates, see: Narayanan Nam-
boothiri, I. N.; Hassner, A.; Gottlieb, H. E. J . Org. Chem. 1997, 62, 485-
492.
(6) For recent examples of stereoselective [3 + 2] cycloaddition involving
a Si-tethered substrate, see: (a) Righi, P.; Marotta, E.; Landuzzi, A.; Rosini,
G. J . Am. Chem. Soc. 1996, 118, 9446-9447. (b) Garner, P.; Cox, P. B.;
Anderson, J . T.; Protasiewicz, J .; Zaniewski, R. J . Org. Chem. 1997, 62,
493-498 and references therein. (c) Denmark, S. E.; Hurd, A. R.; Sacha,
H. J . J . Org. Chem. 1997, 62, 1668-1674.
(7) The identity of the major diastereomers was established by NOE
difference experiments.
(8) For recent reports on protodesilylation of siloxanes, see: (a) Reference
3a. (b) Reference 2a.
(9) (a) Wollenberg, R. H.; Goldstein, J . E. Synthesis 1980, 757-758. (b)
Kozikowski, A. P.; Stein, P. D. J . Am. Chem. Soc. 1982, 104, 4023-4024.
(c) Curran, D. P. J . Am. Chem. Soc. 1982, 104, 4024-4026.
10.1021/jo982180p CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/20/1999

Communications
J . Org. Chem., Vol. 64, No. 3, 1999 693
Ta ble 1. Dia ster eoselective In tr a m olecu la r
Sch em e 3
Vin ylsila n e-Silyln itr on a te Cycloa d d ition sa
Sch em e 4a
a
Conditions: (A) 2 equiv of TMSCl, 2 equiv of Et3N, 22 °C, 12
h, CH2Cl2; (B) 1.1 equiv of PhNCO, 1 mol % of Et3N, C6H6, 70 °C.
b
Isolated yields after silica gel chromatography.
The reaction pathways presented in Scheme 3 suggest a
plausible hypothesis for the observed difference in stereo-
control. The enhanced selectivity in reactions of silyl nitron-
ates (favoring the intermediacy of A) may be due to allylic
1,3 strain involving the appropriate N-O bonds in VII and
VIII; such unfavorable interactions are minimized in VII.
The near-linear geometry of nitrile oxides (IX and X)
precludes such stereodifferentiating elements, and therefore,
C and D are produced indiscriminately. As depicted in
Scheme 3, the intermediacy of VII and VIII is consistent
with the higher levels of selectivity observed with substrates
that bear an R Me group (e.g., 14 vs 6); the steric interaction
that destabilizes VIII is expected to be less pronounced in
the absence of an R substituent.
a
Key: (a) HCl, THF; >98% for both cases; (b) 1.3 equiv of Raney
Ni, MeOH, 1.5 h; 62% and 73% (for 23 and 24, respectively).
cally useful yields.10 As an example, the cycloaddition-
reduction sequence converts nitroalkene 10 to â-siloxy
ketone 25 in ∼50% overall yield (from vinyl silane) and with
complete control of 1,4 relative stereochemistry.
The cycloaddition presented in entry 7 proceeds with
>20:1 stereoselectivity and provides the corresponding five-
membered siloxane 19. This observation indicates that, with
a more labile neighboring alkoxy group, protodesilation may
be initiated under relatively mild conditions. The reaction
in entry 8 (20 f 21) illustrates that the present protocol
allows for efficient control of quaternary stereogenic centers.
In addition to cycloadducts that are protodesilylated in
situ (entries 3 and 7 of Table 1), the C-Si bond in other
reaction products can be readily cleaved upon treatment
with HCl in THF (e.g., 5 f 22 in Scheme 4). As shown in
Scheme 4, the derived isoxazolines may be reduced and
hydrolyzed to afford the corresponding ketones in syntheti-
Ack n ow led gm en t. The National Science Foundation
(CHE-9632278) is acknowledged for support of this re-
search. D.G.J .Y. was a National Institutes of Health
postdoctoral fellow (1F32CA66267-01); E.G.-B. was a Span-
ish Ministry of Education postdoctoral fellow.
Su p p or tin g In for m a tion Ava ila ble: Experimental proce-
dures and spectral data for starting materials and reaction
products.
J O982180P
(10) For reports on the reductive cleavage of N-O bonds in isoxazolines,
see: References 5 and 9.