Tetrahedron Letters
Practical synthesis of 2,5-disubstituted 1,3-dioxolane-4-ones and
highly diastereoselective cis-2,5-disubstituted 1,3-dioxolane-4-ones
from a-hydroxy acids catalyzed by N-triflylphosphoramide
Hatice Baßspınar Küçük
Department of Chemistry, Faculty of Engineering, Istanbul University, 34320 Avcılar, Istanbul, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
N-triflylphosphoramide (NTPA) was found to be an efficient Brønsted acid catalyst for the practical syn-
thesis of 2,5-disubstituted 1,3-dioxolane-4-ones. Racemic and optically pure mandelic acid and lactic acid
could be protected using several aldehydes in high selectivity and moderate yield in the presence of NTPA
without azeotropic distillation or use of a dehydrating reagent.
Received 25 February 2015
Revised 14 August 2015
Accepted 19 August 2015
Available online 20 August 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
2,5-Disubstituted 1,3-dioxolane-4-ones
Cyclocondensation
Acetalization
Brønsted acid catalyst
N-triflylphosphoramide
Mandelic acid
Lactic acid
Introduction
preparation of 1,3-dioxolanones.2b Banik and co-workers have also
reported the molecular iodine-catalyzed protection of
a
-hydroxy
Optically active
a
-hydroxy acids are useful intermediates in the
acids.15 Similarly, the protection of
a-hydroxy acids with aldehy-
synthesis of pharmaceuticals and fine chemicals.1 Additionally
they are valuable starting materials for the asymmetric synthesis
des using (MeO)3CH has been reported by Tanabe et al.16 Finally,
Dunach et al. have synthesized substituted 1,3-dioxolane-4-ones
in a reaction catalyzed by Cu(OTf)2 and Al(OTf)3 which features
of natural products which makes the protection of a-hydroxy acids
an important reaction in many organic synthetic methods.2 Vari-
ous cis-1,3-dioxolane-4-ones (also known as Seebach and Fráter’s
an intramolecular cyclization of a-methylallyloxy carboxylic
acids.17 Success in most cases relies on the azeotropic removal of
water from the reaction medium or addition of a dehydrating
agent. It would therefore be highly desirable if an alternative
method could be employed which overcomes this disadvantage.
In our previous works, we have reported the preparation
of acetals from carbonyl compounds in the presence of
Montmorillonite K-10.18 In order to explore the protection of
chiral templates), obtained from the condensation reaction of
a-
hydroxy acids with an aldehyde, have found use in numerous
stereocontrolled reactions.3 Seebach and co-workers have
described two important reactions, namely the alkylation and aldol
reactions of chiral lithium enolate acetals to generate an additional
chiral center, which is known as self-reproduction of chirality.4
This concept has been applied to the syntheses of natural products
and medicinally important targets.5 Additionally, the syntheses of
gamma-lactams,6 1,4-diketones,7 and 1,3-diketones8 by organocat-
alytic Michael addition, as well as beta-amino acids,9 glycosamino
acids,10 and alpha-hydroxy esters11 have been accomplished.
1,3-Dioxolane-4-ones are most often prepared using Lewis or
Brønsted acid catalysts; e.g., BF3ÁOEt2,12,5a TsOH,13,5a TsOH/
H2SO4,12,5a MsOH,5a TfOH.14,5a Recently, Yamamato et al. used Sc
(OTf)3 and Sc(NTf2)3 as efficient catalysts for the diastereoselective
a
-hydroxy acids, we have examined the potential of N-trifly-
lphosphoramide (phosphoramidic acid) (NTPA) as catalyst.
To the best of our knowledge, there is no report of protection
of -hydroxy acids using N-triflylphosphoramide as the catalyst
a
a
(Fig. 1). As seen from recent reports, achiral, ‘super-acidic’
organic Brønsted acids have been described with similar or
higher reactivities than those of either Lewis or inorganic
Brønsted acids.19 Additionally, Brønsted acids, as compared to
Lewis acids, can be easily handled, are generally stable toward
oxidizing media or moisture, and can be stored over long
periods of time.20
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.