Communications
Investigations to widen the scope of the asymmetric
In conclusion we have developed the first enantioselective
intramolecular crossed-benzoin reaction catalyzed by novel
chiral N-heterocyclic carbenes. The tetracyclic triazolium salt
14 catalyzes the cyclization with generation of a quaternary
stereocenter in high yields and excellent enantiomeric excess.
An interchange of the functional groups of the title a-
hydroxy-substituted tetralones is possible as well as the
synthesis of the corresponding a-hydroxyindanone deriva-
tives with still good enantiomeric excess values.
intramolecular benzoin reaction by utilizing aldehyde-ketone
15, where the aldehyde and the ketone function are inter-
changed relative to 5, show a promising 67% ee for the
resulting acyloin 16 as well as high yields (68%). First
experiments with substrate 17 to synthesize the five-mem-
bered cyclic acyloin 18 resulted in an excellent yield and a
good enantiomeric excess (74%). When the reaction was
carried out at 58C, the enantiomeric excess could be slightly
increased to 75% (Scheme 7).
Experimental Section
Typical procedure for the asymmetric intramolecular crossed-benzoin
reaction, as exemplified for the formation of 6d: Precatalyst 14
(20.6 mg, 0.055 mmol, 20 mol%) was suspended with anhydrous THF
(1.7 mL) in a Schlenk tube under argon at room temperature. A
solution of freshly sublimed KOtBu (5.9 mg, 0.052 mmol, 19 mol%)
in anhydrous THF (0.6 mL) was added slowly, and the solution was
stirred for 5 min. Aldehyde-ketone 5d (60 mg, 0.275 mmol) was
dissolved in anhydrous THF (0.5 mL) and added to the carbene
solution. The reaction mixture was stirred for 48 h, diluted with
CH2Cl2, quenched with water, extracted two times with CH2Cl2, and
dried over MgSO4. The solvent was evaporated and the crude product
was purified by flash chromatography on silica gel (dichloromethane/
n-pentane 2:1) to yield 6d (54 mg, 91%) as a colorless liquid. ee =
98% (determined by HPLC on a chiral stationary phase (Daicel
Chiralpak AD)). [a]D23 = ꢀ30.0 (c = 1.5 in CHCl3); 1H NMR
(300 MHz, CDCl3, TMS): d = 0.85 (d, 3H, J = 6.6 Hz, CH3CH), 0.96
(d, 3H, J = 6.9 Hz, CH3CH), 1.50 (dd, 1H, J = 5.5, 14.3 Hz, CHHCH),
1.68 (dd, 1H, J = 4.7, 14.6 Hz, CHHCH), 1.84–1.97 (m, 1H, CH), 2.15
(ddd, 1H, J = 6.0, 13.5, 13.5 Hz, CCHH), 2.36 (ddd, 1H, J = 2.2, 5.0,
13.5 Hz, CCHH), 2.93–3.17 (m, 2H, CH2), 3.92 (s, 1H, OH), 7.24–
8.00 ppm (m, 4H, ArH); 13C NMR (75 MHz, CDCl3): d = 23.5, 23.7,
24.7, 26.5, 34.7, 43.8, 75.9, 126.7, 127.8, 128.8, 130.4, 133.7, 143.1,
202.5 ppm.
Scheme 7. Further substrate scope for the asymmetric intramolecular
crossed-benzoin reaction. a) 14 (20 mol%), KOtBu (19 mol%), THF
(0.1m), room temperature, 4 days; b) 14 (10 mol%), KHMDS
(10 mol%, 0.5m in toluene), THF (0.1m), 2 days. KHMDS=potas-
sium hexamethyldisilazide.
The absolute configuration of the produced quarternary
stereocenter of the acyloin 6a was determined to be S by
comparison of the measured optical rotation value with the
corresponding literature data.[18] This stereochemical out-
come might be explained by the transition state shown in
Figure 1, which is an adaptation of the transition state
The analytical and spectroscopic data of all new compounds were
correct.
Received: November 3, 2005
Published online: January 3, 2006
Keywords: asymmetric synthesis · benzoin reaction ·
.
heterocycles · homogeneous catalysis · N-heterocyclic carbenes
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Figure 1. Proposed transition state.
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Re face (R ¼
6
Bn). Furthermore, a favorable pre-arrangement
ꢀ
for the formation of the C C bond might be caused by the
activation of the ketone function by an intramolecular
H bridge. Thus, the S configuration of the new stereocenter
would be preferred, which in fact is observed.
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 1463 –1467