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M. Shibuya et al. / Tetrahedron Letters 43 (2002) 4145–4147
and Cu(I) Br-dimethyl sulfide complex in THF, in the
presence of TMS–Cl and HMPA,8 the 1,4-addition
product 10, mp 86–87°C, [h]2D6 +164.2 (c 0.3, CHCl3),
was obtained as a single product after workup with
diluted hydrochloric acid. Since both the 1,4-addition
to the enone 7 and the protonation of the silyl enol
ether intermediate 9 should occur from the convex-face,
the stereochemistry of the a-(1-phenylethyl)ketone 10
was presumed to be the (a-R, b-S) configuration.
(c 0.4, CHCl3), in 62% yield leaving the optically
enriched allyl alcohol (−)-15, [h]2D6 −101.1 (c 0.4, CHCl3)
in 38% yield. The optical purity of the products was
determined as 53 and 96% ee by HPLC (CHIRALCEL
OD, elution with PriOH–hexane, 1:99 for 16 and 1:9 for
15) after conversion into the corresponding p-nitroben-
zoates (Scheme 2).
In order to transform the optically enriched allyl alco-
hol (−)-15 (96% ee) thus obtained into the adamantane
derivative, it was refluxed with dimethylacetamide
dimethyl acetal in diphenyl ether at 280°C to give the
tertiary amide 17, mp 80–81°C, [h]2D8 −15.9 (c 0.8,
CHCl3), stereoselectively, as a single product in 94%
yield. The reaction was presumed to occur exclusively
from the convex-face to give the product 17 having the
b-acetamide configuration which was supported by the
1H NMR spectrum. Namely, the coupling constants
between the vicinal allylic methine proton appeared at
l 2.69 and angular methine proton was very small (<1
Hz), indicating their dihedral angle to be near 90°
which is expected for 17 upon examination of models.
Reduction of the amide 17 with lithium aluminum
hydride proceeded with concomitant removal of the
pivaloyl functionality to give the amino-alcohol 18,
[h]2D8 −15.9 (c 0.8, CHCl3), as a colorless oil. Oxidation
of the amino-alcohol 18 with a catalytic amount of
tetrapropylammonium perruthenate (TPAP)10 in the
presence of N-methylmorpholine N-oxide (NMO) pro-
ceeded without difficulty to give the amino-ketone 19,
[h]2D8 −15.9 (c 0.8, CHCl3), quantitatively. Finally, the
amino-ketone 19 was exposed to Ti(IV) chloride7 as
above to furnish the enantiomerically enriched adaman-
tane (−)-20, [h]2D9 −36.7 (c 0.4, CHCl3), in 62% yield
(Scheme 3).
On exposure to 5 mol% of Ti(IV) chloride in CH2Cl2 at
−30°C, the ketone 10 furnished the saturated adaman-
tane (+)-11, [h]2D5 +72.0 (c 0.9, CHCl3), as a colorless oil
in quantitative yield by facile cyclization while retaining
the stereochemistry of the precursor 10 (Scheme 1).
The second example utilized kinetic resolution during
the Sharpless asymmetric epoxidation.4 The same meso-
ketone 1 was first transformed into the pivalate 13 by
reduction with diisobutylaluminum hydride (DIBAL) in
dichloromethane, followed by treatment of the resulting
endo-alcohol 12, mp 50–55°C, with pivaloyl chloride
under basic conditions. Reaction of the pivalate 13 with
m-chloroperbenzoic acid (m-CPBA) in the presence of
NaHCO3 took place diastereoselectively to give the
epoxide 14, mp 96–98°C, as a single product. It was
found that the rearrangement of the epoxide 14
occurred in a surprisingly facile manner when it was
stirred in chloroform at 30°C for 2 h to furnish the allyl
alcohol ( )-15 in 84% yield. Kinetic resolution was
carried out under catalytic conditions4,9 in the presence
of 15 mol% of diisopropyl L-tartrate (DIPT), 10 mol%
of Ti(IV) isopropoxide and 65 mol% of tert-butyl
hydroperoxide (TBHP) in dichloromethane suspended
,
with molecular sieves (3 A) at −20°C to give the opti-
cally enriched epoxide (+)-16, mp 92–93°C, [h]2D8 +28.2
Ph
H
Ph
H
Ph
O
O
OR
O
iii
H
i
Li
Li
O
O
O
1
2
3
4: R= H
5: R= Ms
ii
n.O.e.
Me
H
α
H
Ph
H
Me
Ph
H
H
H
β
v
H
H
Ph
O–
OMs
O
H
OTMS
O
9
6
7
10
vi
iv
H
OH
OH
Me
H
n.O.e.
H
H
Cl
Cl
(+)-11
(+)-8
Scheme 1. Reagents and conditions: (i) (R,R)-(PhCHMe)2NH, LiCl (2 equiv.), BuLi, THF, −78°C, PhCHO. (ii) Ms–Cl, Et3N,
CH2Cl2. (iii) DBU, toluene (93%, two steps). (iv) TiCl4, CH2Cl2, −30°C (86%). (v) MeLi, CuBr–Me2S, TMS–Cl, HMPA, THF,
−78°C then 10% HCl (91%). (vi) TiCl4, CH2Cl2, −30°C (100%).