Communications
Scheme 4. Synthesis of 6-hydroxymethyl-d-valerolactone (27):
a) TBDPSCl, imidazole, CH2Cl2, 89%; b) PCC, 4-ꢀ MS, CH2Cl2, 508C,
70%; c) TBAF, THF, 08C, 88%. TBDPSCl=tert-butyldiphenylsilyl chlo-
ride, PCC=pyridinium chlorochromate, MS=molecular sieves,
TBAF=tetrabutyl ammoniumfluoride.
oxide is sufficient to accomplish complete conversion of the
starting diene within minutes. The scope of this novel
cyclization method has been extended by the conversion of
the initial cyclization product into a synthetically useful d-
lactone. Further investigations into the mechanism and the
development of an asymmetric variant of this type of
oxidation reaction are currently underway.
Scheme 2. Proposed mechanism for the oxidative cyclization of 1,6-
dienes.
Received: December 22, 2005
Revised: June 1, 2006
Published online: July 24, 2006
Keywords: cyclization · heterocycles · oxidation ·
.
ruthenium tetroxide · tetrahydropyrans
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Scheme 3. Oxidative cyclization of chiral 1,6-dienes: a) 5 mol% RuCl3,
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selectivity of this transformation is not satifactory it should be
noted that enantiomerically pure products with two new
stereogenic centers are accessible after separation.
We next sought to extend the scope of this new oxidative
cyclization by seeking conditions to convert the 2,6-
bis(hydroxymethyl)tetrahydropyrans into d-lactones. The
primary hydroxy function of the cyclization product 2
(which could be prepared on a gram scale) was first protected
(Scheme 4). Conditions for the oxidative cleavage of the
tertiary hydroxy methyl group were then investigated.
Pyridinium chlorochromate (PCC)[18] proved to be the most
efficient reagent for this purpose, and the oxidative cleavage
to d-lactone 26 proceeded smoothly (70% yield). Fluoride-
induced deprotection provided the free alcohol 27 in an
overall yield of 47% (over 4 steps) starting from commer-
cially available diene 1. This d-lactone has previously been
used as a key intermediate in natural product synthesis.[19]
In summary, the first general and efficient procedure for
the oxidative cyclization of 1,6-dienes has been presented.
The cyclization products were obtained in good to high yields
and excellent diastereoselectivity. 1–5 mol% ruthenium tetr-
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 6218 –6221