TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1017–1019
Enantioselective desymmetrization of a phospholene
meso-epoxide
K. Michał Pietrusiewicz,a,b,* Marek Koprowskic and Zbigniew Pakulskib
aDepartment of Organic Chemistry, Maria Curie-Skłodowska University, Gliniana 33, 20-614 Lublin, Poland
bInstitute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warszawa, Poland
cCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Ło´dz, Poland
Received 26 April 2002; accepted 16 May 2002
Abstract—Cinchona alkaloids serve as effective chiral bases in the enantioselective rearrangement of 3-phospholene epoxide. The
reaction results in the formation of a P,C-chirogenic 3-hydroxy-2-phospholene derivative with up to 52% e.e. A stereochemical
course for the epoxide rearrangement involving anti-b-proton abstraction is implied. © 2002 Elsevier Science Ltd. All rights
reserved.
Asymmetric rearrangements of achiral epoxides to
enantiomerically enriched allylic alcohols by the action
of chiral organolithium bases has recently emerged as
one of the most useful methodologies in the field of
asymmetric synthesis.1 It is accepted that these rear-
rangements proceed via initial lithium coordination to
the epoxy oxygen followed by abstraction of a syn-b-
proton.2 In the last two decades a number of successful
strategies based on this transformation have been devel-
oped for targeted syntheses of enantiomerically
enriched cyclic and acyclic compounds containing car-
bon stereogenic centers.1,3
effective catalysts for enantioselective epoxide rear-
rangement reactions,7–10 such as LDA/(S)-(+)-1-(2-
pyrrolidinylmethyl)pyrrolidine,
sec-BuLi/sparteine,
n-BuLi/sparteine or n-BuLi/bis[(S)-1-phenylethyl]-
amine, afforded the desired hydroxyphospholene 3 in
good chemical yields (53–79%) but with very poor or
no asymmetric induction (0–8% e.e.).
More promising results were obtained when Cinchona
alkaloids were used as free amine catalysts for the
rearrangement:test reactions with these bases were car-
ried out at 20°C or 55−60°C using 0.5 or 1.0 equiv. of
base in ethanol or dichloromethane and were typically
completed over prolonged reaction times in order to
achieve higher conversions. The results of the screening
in dichloromethane, which proved to be the better
solvent are presented in Table 1.
In the course of our research program directed towards
the synthesis of P-chirogenic monophosphines4 we
wanted to utilize this methodology to create a phospho-
rus stereogenic center embedded within a five-mem-
bered ring. We chose 3-phospholene epoxide 2 as a
suitable substrate as it is readily available in
diastereomerically pure form by a literature procedure
involving oxidation of 1-phenyl-3-phospholene oxide 1
with m-chloroperbenzoic acid.5,6 It is also already
known that epoxide 2 rearranges efficiently to 3-
hydroxy-2-phospholene 3 in the presence of triethyl-
amine in refluxing ethanol.5 We anticipated that the use
of a chiral base in lieu of triethylamine would result in
an efficient asymmetric synthesis of 3 (Scheme 1).
As shown in Table 1, the highest enantiomeric purities
of alcohol 3 were obtained in the reactions performed
in the presence of quinidine (52% e.e., entry 8) and
cinchonine (47% e.e., entry 6) which both favored the
Treatment of epoxide 2 in Et2O or THF solutions at
−78°C with chiral base systems known to be very
Scheme 1. Reagents and conditions: (i) 1.5 equiv. m-CPBA,
CHCl3, reflux, 10 h, 84%; (ii) base, see Table 1.
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00245-8
Pietrusiewicz
