Communications
pressure to afford the crude allylic alcohol. Purification of the residue
by flash column chromatography on silica gel afforded the desired
product.
4) and electron-rich (Table 2, entries 5 and 6) aryl-substituted
allylic carbonates can be used as the starting materials for the
transformation. The subsequent cleavage of the silyl ether
proceeds uneventfully to yield chiral alcohols in 64–88%
yield and with 92–98% ee. Notably, the cleavage is conven-
iently carried out using TBAF in THF. However, a simple
deprotection of the crude material with 30% aqueous NaOH
in MeOH also allows straightforward access to chiral allylic
alcohols. The process tolerates substrates with additional
functional groups (for acetals, compare Table 2, entries 6 and
7) without showing any deleterious impact on the yield or
enantioselectivity. Furthermore, the reaction can be carried
out with heterocyclic-substituted allylic carbonates. Thus,
thiophene- (Table 2, entries 8 and 9) and furan-substituted
allylic alcohols (Table 2, entries 10 and 11) can be obtained in
good yields and excellent enantioselectivities (97–99% ee).
The reaction of a dienyl carbonate proceeds to give products
with high regio- and enantioselectivity (Table 2, entry 12).
The method is also tolerant of alkyl-substituted allylic
carbonates (Table 2, entry 13).[18]
In conclusion, we have reported the first highly regio- and
enantioselective Ir-catalyzed allylic etherification of a wide
range of achiral allylic carbonates substituted with aryl and
alkyl groups, by using potassium silanolates as the nucleo-
philes. Subsequent cleavage of the silyl ether of the TES
adducts gives rapid and reliable access to chiral allylic
alcohols in high yields and enantioselectivities. Stable silyl
ethers (TBS, TIPS), which can be carried through multistep
reaction sequences, can also be formed in excellent yields and
enantioselectivities. The fact that optically active allylic
alcohols are easily accessed with this methodology opens up
new avenues for the synthesis of complex molecules by Ir
catalysis. Additionally, the use of silanolates may be of
interest in other carbon–oxygen bond-forming reactions.
Further exploration of this methodology and its application
in synthesis is underway, and will be reported in due course.
Received: June 15, 2006
Published online: August 17, 2006
Keywords: alcohols · allylic compounds · asymmetric catalysis ·
.
iridium · nucleophilic substitution
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Experimental Section
Representative procedure: A Schlenk flask under argon was charged
with [{Ir(cod)Cl}2] (10.1 mg, 15 mmol, 3 mol%) and (S)-(+)-(3,5-
dioxa-4-phosphacyclohepta[2,1-a;3,4-a’]dinaphthalen-4-yl)bis[(1S)-1-
phenylethyl]amine (Feringa phosphoramidite) (16.2 mg, 30 mmol,
6 mol%). THF (0.5 mL) and n-propylamine (0.5 mL) were added,
and the reaction mixture was stirred at 508C for 30 min. The solution
was allowed to cool to RT and the volatiles were removed under high
vacuum (30 min). A solution of potassium silanolate (1.00 mmol,
2 equiv) in CH2Cl2 (2 mL) was added, followed by tert-butyl
carbonate (0.50 mmol, 1 equiv) in CH2Cl2 (2 mL), and the reaction
mixture was stirred at RT. After completion of the reaction (usually
14 h), as determined by TLC, the crude mixture was partitioned
between H2O (20 mL) and CH2Cl2 (20 mL). The aqueous layer was
then extracted with CH2Cl2 (3 15 mL). The combined organic layers
dried (Na2SO4) and concentrated under reduced pressure to afford
the crude silyl ether. The ratio of regioisomers was determined by
1H NMR analysis of the unpurified sample. The mixture was then
dissolved in THF (5 mL), cooled to 08C, and treated with TBAF (1m
in THF, 1 mL, 2 equiv). The reaction mixture was stirred for 2 h, then
partitioned between H2O (50 mL) and CH2Cl2 (20 mL). The aqueous
layer was then extracted with CH2Cl2 (3 15 mL). The combined
organic layers were dried (Na2SO4) and concentrated under reduced
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 6204 –6207