Communications
and the vial was sealed with a cap containing a PTFE septum and
removed from the drybox. The vial was placed in an ice-water bath,
and tert-butyl carbonate (0.50 mmol) was added to the reaction
mixture by syringe. The reaction mixture was slowly warmed to room
temperature over 4 h. After the reaction was complete (determined
by GC and TLC) the crude mixture was passed through a pad of silica
gel (EtOAc/hexanes 10:90), and the resulting solutions were con-
centrated. The ratio of regioisomers was determined by 1H NMR
spectroscopy of the crude sample. The mixture was then purified by
flash column chromatography on silica gel to give the desired product.
Indeed, reactions of the alkoxide derived from (S)-1-(2-
naphthyl)ethanol (2i) with allylic carbonates (1a, 1 f) cata-
lyzed by iridium complexes containing opposite enantiomers
of ligand L2 formed the opposite diastereomers of the allylic
ether with excellent yields, regio- and diastereoselectivities
(entries 10–13). The reaction was not constrained by a match
and mismatch of the substrate and catalyst chirality.
The control of enantio- and diastereoselectivity is appli-
cable to the synthesis of cis- and trans-2,5-disubstituted
dihydrofurans and cis- and trans-2,6-disubstituted dihydro-
pyrans[28,29] with control of absolute and relative stereochem-
istry with readily available, enantioenriched allylic[30,31] and
homoallylic alcohols[32,33] (Scheme 2). For example, 1a and 1e
Received: April 3, 2004
Revised: May 18, 2004
Keywords: alkoxides · allylations · asymmetric synthesis ·
.
iridium · P ligands
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Soc. 2004, 126, 1628.
Scheme 2. Synthesis of disubstituted dihydrofurans and dihydropyrans.
Ar=p-MeOC6H4, Cy=cyclohexyl.
[10] C. Thorey, J. Wilken, F. Henin, J. Martens, T. Mehler, J. Muzart,
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reacted with alkoxides derived from (R)-1-octen-3-ol and (S)-
4-penten-2-ol, respectively, in the presence of catalysts
derived from the two enantiomers of L2 to form the branched
allylic ethers 5, 5’ and 6, 6’ with excellent yields and regio- and
diastereoselectivities. Ring-closing metathesis[34] with the
Grubbs catalyst 7[35] proceeded smoothly to give the corre-
sponding cyclic ethers 8, 8’ and 9, 9’ in high yields and with
retention of configuration.[36]
In summary, we have developed the first general and
highly selective allylic etherification with both primary and
secondary aliphatic alkoxides. The ability of the catalyst to
control the newstereocenter generated from the reaction of
chiral secondary alkoxides makes possible highly enantiose-
lective and diastereoselective routes to ethers and oxygen
heterocycles that have been challenging to prepare in
uncatalyzed reactions.
[14] H. Kim, C. Lee, Org. Lett. 2002, 4, 4369.
[15] P. A. Evans, D. K. Leahy, J. Am. Chem. Soc. 2002, 124, 7882.
[16] T. Ohmura, J. F. Hartwig, J. Am. Chem. Soc. 2002, 124, 15164.
[17] F. Lopez, T. Ohmura, J. F. Hartwig, J. Am. Chem. Soc. 2003, 125,
3426.
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Soc. 2003, 125, 14272.
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2003, 1097.
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2003, 14, 3613.
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[26] The absolute configuration of the product was established by
comparison with the R configured ether prepared from com-
mercial (R)-1-phenylpropanol.
[27] J. Buckingham, Dictionary of Natural Products, University Press,
Cambridge, MA, 1994.
[28] W. Friedrichsen in Comprehensive Heterocyclic Chemistry, Vol. 2
(Ed.: C. W. Bird), Elsevier, Oxford, UK, 1996, p. 386.
Experimental Section
Representative procedure. In a drybox, lithium alkoxide (1.00 mmol)
and CuI (200 mg, 1.05 mmol) were mixed in a screw-capped vial. THF
(1.0 mL) was added, and the suspension was stirred for 30 min. To this
suspension was added
a solution of [{Ir(cod)Cl}2] (3.4 mg,
0.0051 mmol for primary alkoxides; 6.7 mg, 0.010 mmol for secondary
and tertiary alkoxides) and (Ra,Rc,Rc)-L2 (6.4 mg, 0.010 mmol for
primary alkoxides; 12.8 mg, 0.020 mmol for secondary and tertiary
alkoxides) in THF (0.5 mL for primary alkoxides; 1.0 mL for
secondary and tertiary alkoxides). A magnetic stir bar was added,
4796
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Angew. Chem. Int. Ed. 2004, 43, 4794 –4797