Stereoselective Cyclization of Highly Enantioenriched Allylsilanes with Aldehydes via Acetal Formation: New Asymmetric Access to Tetrahydropyrans and Piperidines

Full text of DOI:10.1021/jo981173y

6096
J . Org. Chem. 1998, 63, 6096-6097
Sch em e 1a
Ster eoselective Cycliza tion of High ly
En a n tioen r ich ed Allylsila n es w ith Ald eh yd es
via Aceta l F or m a tion : New Asym m etr ic
Access to Tetr a h yd r op yr a n s a n d P ip er id in es
Michinori Suginome, Taisuke Iwanami, and
Yoshihiko Ito*
Department of Synthetic Chemistry and Biological Chemistry,
Graduate School of Engineering, Kyoto University,
Kyoto 606-8501, J apan
Received J une 22, 1998
Allylsilanes are the practically applicable building block
for selective organic synthesis, being utilized for efficient and
selective carbon-carbon bond formation with various cat-
ionic electrophiles.1 Of particular use is that allylsilanes
having a chiral center at the allylic carbon atom adjacent
to the silicon atom undergo regio- and stereoselective
carbon-carbon bond formation with the 1,3-chirality trans-
fer.2,3 However, the potential usefulness of intramolecular
cyclization with optically active allylsilanes has not been
exploited because of the synthetic inaccessibility of optically
active allylsilanes having functional groups.3-5
a
Reagents and Conditions: (a) ClPh2SiSiMe2Ph, Et3N, THF, rt, 93%
(3a ) and 99% (3b); (b) Pd(acac)2 (0.02 equiv), t-OcNC (0.15 equiv),
toluene, reflux; (c) n-BuLi, 0 °C, 73% (4a ) and 75% (4b); (d) PPTS (0.2
equiv), EtOH, 55 °C, 96% (1a ) and 90% (1b).
The allylsilanes 1 having a hydroxy group thus prepared
were reacted with isobutyraldehyde (1 molar equiv) in the
presence of trimethylsilyl triflate (TMSOTf, 1.1 molar equiv)
at -78 °C in CH2Cl2 to afford the corresponding cyclic ethers
5 and 6 (eqs 2 and 3).9 The intramolecular cyclization
Recently, we have reported a new synthetic method for
highly enantioenriched (E)-allylsilanes having a stereogenic
carbon adjacent to the silicon.6 The new synthesis of
optically active allylsilanes, which involves an intramolecu-
lar bis-silylation of optically active allylic alcohols, proceeds
with highly stereoselective 1,3-chirality transfer, producing
optically active (E)-allylsilanes without loss of the enantio-
meric excesses of the starting alcohols (eq 1).
reactions may involve oxonium ion intermediates generated
via the acetal formation from 1 and aldehydes. The stereo-
chemical discrepancy between the cyclic ethers 5 and 6 is
worth noting: 1a afforded exclusively cis-2,3-disubstituted
tetrahydrofuran, which is a 1:1 mixture of E and Z isomers
with respect to the olefin geometry, while 1b gave only trans-
2,3-disubstituted tetrahydropyran with an (E)-carbon-
carbon double bond.10 The stereochemical outcome suggests
that diastereofacial selection at the CdC as well as the Cd
Herein, we describe stereoselective synthesis of enan-
tioenriched (E)-allylsilanes bearing hydroxy and amino
functionalities, which undergo intramolecular allylation via
acetal or aminal formation under acidic conditions, giving
highly enantioenriched 2,3-disubstituted cyclic ethers and
amines, respectively. Since the related heterocyclic struc-
tures are involved in many naturally occurring compounds
in enantiomerically pure forms, development of facile access
to the heterocycles is highly desirable. For instance, ac-
cording to the procedure reported by us,6 racemic disilanyl
ethers 3a and 3b, which were prepared from the corre-
sponding allylic alcohols with the terminal hydroxy groups
protected by THP, were subjected to the intramolecular bis-
silylation catalyzed by palladium isonitrile complex at 110
°C,7 followed by treatment of the resulting reaction mixture
with n-BuLi at 0 °C to give the expected allylsilanes 4a and
4b in good yields (Scheme 1).8 Subsequent deprotection of
the THP was carried out by a catalytic amount of pyridinium
p-toluenesulfonate in ethanol at 55 °C to afford allylsilanes
1a and 1b in high yields.
O
+ is highly controlled for the intramolecular allylation with
1b rather than 1a .
Next, enantioenriched allylsilane (S)-1b of 93.2% ee,11
prepared from the allylic alcohol (R)-2b of 93.6% ee, which
is synthetically available by the Sharpless procedure (eq 4),12
was subjected to the intramolecular cyclization under condi-
tions identical to those for racemic 1b (Table 1). As expected,
reaction with isobutyraldehyde furnished the trans-2,3-
(7) (a) Suginome, M.; Ito, Y. J . Chem. Soc., Dalton Trans. 1998, 1925-
1934. (b) Suginome, M.; Ito, Y. J . Synth. Org. Chem. J pn. 1997, 55, 1040-
1051. (c) Ito, Y.; Suginome, M.; Murakami, M. J . Org. Chem. 1991, 56, 1948-
1951. (d) Suginome, M.; Takama, A.; Ito, Y. J . Am. Chem. Soc. 1998, 120,
1930-1931.
(8) Peterson, D. J . J . Org. Chem. 1968, 33, 780-784.
(1) Fleming, I.; Dunogues, J .; Smithers, R. Org. React. 1989, 37, 57-
575. Sarkar, T. K. Synthesis 1990, 969-983. Sarkar, T. K. Synthesis 1990,
1101-1111.
(2) Hayashi, T.; Konishi, M.; Kumada, M. J . Am. Chem. Soc. 1982, 104,
4963. Hayashi, T.; Konishi, M.; Kumada, M. J . Org. Chem. 1983, 48, 281-
282.
(9) Marko´, I. E.; Mekhalfia, A. Tetrahedron Lett. 1992, 33, 1799-1802.
Marko´, I. E.; Bayston, D. J . Tetrahedron Lett. 1993, 34, 6595-6598. Marko´,
I. E.; Bayston, D. J . Tetrahedron 1994, 50, 7141-7156. Marko´, I. E.; Bailey,
M.; Murphy, F.; Declercq, J . P.; Tinant, B.; Feneau-Dupont, J .; Krief, A.;
Dumont, W. Synlett 1995, 123-126. Mohr, P. Tetrahedron Lett. 1993, 34,
6251-6254. Oriyama, T.; Ishiwata, A.; Sano, T.; Matsuda, T.; Takahashi,
M.; Koga, K. Tetrahedron Lett. 1995, 36, 5581-5584. Sano, T.; Oriyama,
T. Synlett 1997, 716-718.
(3) Masse, C. E.; Panek, J . S. Chem. Rev. 1995, 95, 1293-1326.
(4) Mikami, K.; Maeda, T.; Kishi, N.; Nakai, T. Tetrahedron Lett. 1984,
25, 5151-5154.
(10) For the stereochemical assignments, see the Supporting Information.
(11) The enantiomeric excess of (S)-1b was determined by the reported
procedure involving regio- and stereoselective hydroboration with 9-BBN
followed by oxidation. See ref 7b. For the reaction of allylsilanes with 9-BBN,
see: Fleming, I.; Lawrence, H. J . J . Chem. Soc., Perkin Trans. 1 1992, 3309-
3326.
(5) Tietze, L. F. Chem. Rev. 1996, 96, 115-136.
(6) (a) Suginome, M.; Matsumoto, A.; Ito, Y. J . Am. Chem. Soc. 1996,
118, 3061-3062. (b) Suginome, M.; Iwanami, T.; Matsumoto, A.; Ito, Y.
Tetrahedron: Asymmetry 1997, 8, 859-862. (c) Suginome, M.; Matsumoto,
A.; Ito, Y. J . Org. Chem. 1996, 61, 4884-4885.
S0022-3263(98)01173-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/08/1998

Communications
J . Org. Chem., Vol. 63, No. 18, 1998 6097
Ta ble 1. Asym m etr ic Syn th esis of Tetr a h yd r op yr a n s by
Ster eoselective Cycliza tion of En a n tioen r ich ed
Allylsila n e (S)-1b w ith Ca r bon yl Com p ou n d sa
cyclization with the CdC bond. Notable is that use of CH3-
CN solvent with the decreased amount of TMSOTf to 0.1
equiv successfully led to the expected formation of 6g of
92.0% ee in 72% yield along with bicyclic 7 in less than 5%
yield (entry 7). No formation of 5-decen-1-ol, which may
arise from protodesilylation of the starting allylsilane, was
observed in any case.
The 2,3-trans stereochemistry in the six-membered cyclic
products 6 indicates that the intramolecular cationic ally-
lation proceeds through a chairlike transition state, in which
the R group of the aldehyde and the CdC bond occupy the
equatorial positions (eq 6). Furthermore, the absolute (S)-
configuration at the 3-position in 6b, which was determined
according to the Trost’s procedure,15 reveals that the in-
tramolecular allylation takes place at the CdC π-face anti
to the silyl group.
carbonyl compd
entry
R
R′ product 6 yield/% trans/cisb eec/%
1d
2
3
4
5
Me
H
b
c
a
d
e
f
89
92
98
99
88
95
72
>10:1
>10:1
99:1
99:1
9:1
93.4
92.1
92.8
92.3
93.6
91.5
92.0
n-Hex
i-Pr
H
H
cyclo-Hex
t-Bu
H
H
6
Me
CHdCMe2
Me
H
7e
g
12:1
a
(S)-1b (93.2 ( 0.2% ee), carbonyl compounds (1.1 equiv), and
TMSOTf (1.1-2 equiv) were reacted in CH2Cl2 at -78 °C unless
otherwise noted. b Stereochemistry in the six-membered ring. c The
values ((0.2) were determined by HPLC (entries 2-7) or GC (entry
d
1). Acetaldehyde diethyl acetal was used. e Reaction in CH3CN
at -30 °C to rt in the presence of TMSOTf (0.1 equiv).
The present methodology involving acetal formation fol-
lowed by intramolecular allylation was applicable to the
asymmetric synthesis of a piperidine derivative.16 Azidation
and subsequent reduction of (S)-1b afforded optically active
allylsilane (S)-8 having an amino functionality in good yield
(eq 7). Although the cyclization reaction of (S)-8 with
disubstituted THP derivative 6a of 92.8% ee (entry 3),13
indicating the intramolecular cyclization proceeded with
nearly complete (>99%) chirality transfer. Cyclohexanecar-
boxaldehyde also provided enantioenriched trans-2,3-disub-
stituted THP (6d ) diastereoselectively (entry 4). Acetalde-
hyde diethyl acetal as well as heptanal and pivalaldehyde
afforded enantioenriched trans-2,3-disubstituted THP (6b,c,e)
but with the respective cis isomers in ratios of g9:1 (entries
1, 2, and 5). Similarly, acetone underwent the cyclization
to give product 6f of 91.5% ee in high yield (entry 6).
Unexpectedly, the intramolecular allylation with R,â-
unsaturated aldehyde under identical reaction conditions
gave bicyclic organosilicon derivative 7 as a single diaste-
reomer in moderate yield (eq 5). The cyclization may
isobutyraldehyde hardly proceeded in the presence of TM-
SOTf, the reaction in the presence of CF3CO2H in refluxing
CH3CN gave trans-2,3-disubstituted piperidine 9 in high
yield (88%). The high ee of 9 reveals that the piperidine
ring formation also takes place with highly effective chirality
transfer as shown for the formation of THP derivatives.
In summary, the new optically active allylsilanes with an
hydroxy as well as an amino group were found to serve as
highly useful tools for the synthesis of optically active six-
membered ring heterocycles from aldehydes through the
effective chirality transfer.
Su p p or tin g In for m a tion Ava ila ble: Detailed experimental
procedures and characterization of the new compounds, including
determination of the enantiomeric excesses of the enantioenriched
compounds (10 pages).
proceed through [1,2]-migration of the silyl group in the
â-silyl cationic species initially formed,14 followed by a second
(12) (a) Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada, Y.; Ikeda,
M.; Sharpless, K. B. J . Am. Chem. Soc. 1981, 103, 6237-6240. (b) Gao, Y.;
Hanson, R. M.; Klunder, J . M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B.
J . Am. Chem. Soc. 1987, 109, 5765-5780. Enantioenriched (R)-2b of 93.6%
ee was obtained by the kinetic resolution at 0 °C (L-(+)-DIPT, TBHP 0.6
equiv) and used for the synthesis of (S)-1b. The ee was, however, found to
be improved to 98.5% by carrying out the resolution at -20 °C.
(13) The enantiomeric excesses described in this paper were determined
by HPLC or GC analyses ((0.2%) with chiral columns. For the determi-
nation of those for 6, the analyses were carried out for N-(3,5-dinitrophenyl)-
carbamates of the corresponding 2-substituted tetrahydropyran-3-ylmeth-
anol derivatives, which are prepared by oxidative cleavage of the CdC bonds
(OsO4, NMO, then HIO4) followed by reduction with NaBH4. The chiral
columns used are specified in the Supporting Information.
J O981173Y
(14) For examples, see: Danheiser, R. L.; Carini, D. J .; Basak, A. J . Am.
Chem. Soc. 1981, 103, 1604-1606. Kno¨lker, H.-J .; J ones, P. G.; Pannek,
J .-B. Synlett 1990, 429. Also see refs 3 and 7d.
(15) The mandelate procedure reported by Trost et al. was applied to
trans-2-hexyltetrahydropyran-3-ol, which was derived from 6b. For the
transformation, see the Supporting Information. Trost, B. M.; Belletire, J .
L.; Godleski, S.; McDougal, P. G.; Balkovec, J . M. J . Org. Chem. 1986, 51,
2370-2374.
(16) (a) Grieco, P. A.; Fobare, W. F. Tetrahedron Lett. 1986, 27, 5067-
5070. (b) Hiemstra, H.; Fortgens, H. P.; Speckamp, W. N. Tetrahedron Lett.
1985, 26, 3155-3158.