HIGHLIGHT
“This is the peer reviewed version of the following article: ChemCatChem 2015, 7, 51-53, which has been published in final form at
DOI: 10.1002/cctc.201402801. This article may be used for non-commercial purposes in accordance with Wiley Terms and
Conditions for Self-Archiving published at http://olabout.wiley.com/WileyCDA/Section/id-820227.html."

HIGHLIGHT
Diastereo- and Enantioselective Valorization of Cyclic Organic
Carbonates
Arjan W. Kleij[a,b] and Christopher J. Whiteoak*[c]
The synthesis of 1,3-dioxolan-2-ones, more commonly referred to
as cyclic organic carbonates, has been attracting significant
attention. This is largely a result of their growing application
potential, for example, as electrolytes in lithium ion batteries, polar
aprotic solvents and fuel additives.[1] To date, a number of
strategies predominantly based on carbon dioxide (CO2)
utilization have been developed for their synthesis[2] and
consequently a variety of cyclic organic carbonates containing
diverse functionalities are now synthetically available.[3] Despite
having access to a library of high-potential synthons and efficient
catalyst systems for their preparation,[3b,4] surprisingly little
attention has been directed towards the application of these
organic carbonates as precursors in synthetic organic chemistry.
Recently, several reports have focused on the stereoselective formation of vicinal cis-diols, using cyclic organic
carbonate precursors as intermediates to steer the
stereoselectivity of the reaction.[5] In these examples, a cis-cyclic
epoxide is initially transformed into the corresponding cis-cyclic
organic carbonate intermediate with excellent retention of
stereochemical information through coupling with CO2, using nonchiral catalyst systems based on Fe or Al complexes. Treatment
of the cis-cyclic organic carbonates with a suitable base furnishes
the vicinal cis-diol products with high stereoselectivity,
showcasing the versatile use of these organic carbonates for the
synthesis of value-added compounds.
In an elegant but different approach, Trost and co-workers
reported on the decarboxylative coupling of 1,2-divinylethylene
carbonates (VECC; Scheme 1) with phthalimides. The reaction
utilizes the pendent vinylethylene functionalities of the cyclic
organic carbonate scaffolds as a directing group with the reaction
proceeding through a π-allyl-palladium intermediate. This
intermediate is key to the enantioselective outcome of the reaction
as rapid isomerization of the π-allyl-palladium intermediates,
directed by a chiral phosphine ligand results in a Dynamic Kinetic
Asymmetric Transformation (DYKAT).[6] A similar approach was
also described by Krische and co-workers who have reported on
an Ir-catalyzed transfer hydrogenation of a VECC using
aldehydes and alcohols as reaction partners realizing valuable
chiral 1,3-diol motifs in high diastereo- and enantioselectivities
through
a
formal
decarboxylative
carbonyl
(hydroxymethyl)allylation.[7]
The preparation of complex chiral building blocks from
racemic starting materials remains a key strategy for the synthesis
of natural products due to the expense of chiral precursors. Whilst
the two latter examples mentioned above have indicated the

[a]
[b]

[c]

Prof. Dr. A. W. Kleij, Institute of Chemical Research of Catalonia
(ICIQ), Av. Països Catalans 16, 43007 – Tarragona (Spain)
Prof. Dr. A. W. Kleij, Catalan Institute of Research and Advanced
Studies (ICREA), Pg. Lluïs Companys 23, 08010 – Barcelona
(Spain)
Dr. C. J. Whiteoak, Institut de Química Computacional i Catàlisi
(IQCC), Universitat de Girona, Campus de Montilivi, 17071 – Girona
(Spain); E-mail: christopher.whiteoak@udg.edu

potential of VECC’s as starting materials for the synthesis of chiral
synthons using decarboxylative strategies, the scope of coupling
partners still remains an open though expedient challenge.

Scheme 1. (a) Pd-catalyzed asymmetric decarboxylative coupling of Michael
acceptors and racemic substituted VECC’s for the formation of chiral
multifunctionalized tetrahydrofurans. (b) Examples of chiral multifunctionalized
tetrahydrofurans obtained.

Recently, Zhang and co-workers have reported on the Pdcatalyzed asymmetric decarboxylative coupling of racemic
substituted VECC’s with Michael acceptors (Scheme 1a)[8]
making a significant contribution to expand on the use of VECC’s
as precursors in asymmetric synthesis. This reaction provides
simple access to chiral, highly-functional tetrahydrofurans
containing two quaternary stereo-centres, in high yields and with
high levels of diastereo- and enantioselectivity (Scheme 1b). The
high enantioselectivity of the products again originates from the
use of a matching chiral ligand, in this case a phosphoramidite
ligand, (S)-L1. Interestingly, the compounds derived from
couplings with methylenemalononitriles reagents (R3 = R4 = CN)
can be easily hydrolyzed in a one-pot procedure to furnish the
corresponding chiral amino acids, exemplifying the potential of

HIGHLIGHT
these chiral tetrahydrofurans as practical and accessible
synthons for the synthesis of natural products.

kind of coupling reactions with VECC’s, controlling the
diastereoselectivity remains so far a challenge. While the
chemistry centring around the use of VECC’s has grown
tremendously, identification of new and useful coupling partners
and the realization of high diastereo- and enantioselectivity is
requisite to them becoming a common precursor in synthetic
organic chemistry. The use of alternative organic carbonate
synthons with directional functional groups may offer further
potential for expanding on the scope of chiral molecules that can
be attained from these simple precursors.
Herein, new exciting examples of the potential application of
functionalized cyclic organic carbonates as valuable precursors in
synthetic organic chemistry have been discussed. The recent
examples using Pd-catalyzed decarboxylative coupling of
racemic VECC’s with formaldehyde or activated Michael
acceptors as coupling partners exemplify the potential for easily
constructing complex molecules in a single conversion, providing
potential building blocks for natural product and pharmaceutical
drug synthesis. This highlight should serve to alert other
researchers to the potential of using easily prepared, functional
cyclic carbonates in synthetic organic chemistry. The application
of six-membered cyclic organic carbonates and also further
amplification of the nature of the coupling partners likely provides
interesting topics for further investigation.

Acknowledgements
Scheme 2. (a) Pd-catalyzed asymmetric decarboxylative coupling of racemic
substituted VECC’s with formaldehyde for the synthesis of (R)-1,3-dioxolanes
and conversion to (R)-tertiary vinylglycols. (b) Examples of (R)-1,3-dioxolanes
and (R)-tertiary vinylglycols that have been obtained.

The same authors have also recently applied another
coupling partner, namely formaldehyde, furnishing (R)-1,3dioxolanes with high enantioselectivities and yields (Scheme 2).[9]
The (R)-1,3-dioxolane intermediates can be easily converted into
the corresponding chiral vicinal diols without loss of
stereochemical information in the final hydrolysis step. This
procedure thus provides a facile two-step route towards a range
of chiral vicinal diols with variable functionality raising the potential
for application in natural product and pharmaceutical drug
preparation. In particular, the authors have indicated that a (R)1,3-dioxolane with a -(CH2)10CH3 substituent could be
successfully used as a chiral building block in the synthesis of the
natural product Tanikolide. Alternatively, the (R)-1,3-dioxolane
containing a 2,4-difluorobenzene group could be employed for the
preparation of antifungal agents such as Genaconazole,
Ravuconazole and Albaconazole.
When aldehydes are used as reaction partners it is also
possible to effectively form cyclized products with high
enantioselectivity, though with limited diastereoselectivity.[9] Thus,
although other reaction partners are shown to be useful in these

The authors thank ICIQ, ICREA and the Spanish MINECO
(CTQ2011-27385) for support.
Keywords: Cyclic Carbonates • Decarboxylation • Asymmetric
catalysis • Palladium catalysis • Synthetic methodology
[1]
[2]
[3]

[4]
[5]

[6]
[7]
[8]
[9]

T. Sakakura, K. Kohno, Chem. Commun. 2009, 11, 1312. (b)
M. North, R. Pasquale, C. Young, Green Chem. 2010, 12, 1514.
For examples of methods to prepare highly-functionalized cyclic
carbonates using CO2 see: (a) M. Yoshida, M. Fujita, T. Ishii, M. Ihara, J.
Am. Chem. Soc. 2003, 125, 4874. (b) C. J. Whiteoak, N. Kielland, V.
Laserna, E. C. Escudero-Adán, E. Martin, A. W. Kleij, J. Am. Chem. Soc.
2013, 135, 1228. (c) A. K. Buzas, F. M. Istrate, F. Gagosz, Tetrahedron
2009, 65, 1889. (d) S. Minakata, I. Sasaki, T. Ide, Angew. Chem. Int. Ed.
2010, 49, 1309. (e) P. Yan, X. Tan, H. Jing, S. Duan, X. Wang, Z. Liu, J.
Org. Chem. 2011, 76, 2459.
T. Ema, Y. Miyazaki, J. Shimonishi, C. Maeda, J.-Y. Hasegawa, J. Am.
Chem. Soc. 2014, DOI: 10.1021/ja507665a.
(a) V. Laserna, G. Fiorani, C. J. Whiteoak, E. Martin, E. C. EscuderoAdán, A. W. Kleij, Angew. Chem. Int. Ed. 2014, 53, 10416. (b) C. Beattie,
M. North, P. Villuendas, C. Young, J. Org. Chem. 2013, 78, 419.
B. M. Trost, A. Aponick, J. Am. Chem. Soc. 2005, 128, 3931.
Y. J. Zhang, J. H. Yang, S. H. Kim, M. J. Krische, J. Am. Chem. Soc.
2010, 132, 4562.
A. Khan, L. Yang, J. Xu, L. Y. Jin, Y. J. Zhang, Angew. Chem. Int. Ed.
2014, 53, DOI: 10.1002/anie.201407013.
A. Khan, R. Zheng, Y. Kan, J. Ye, J. Xiang, Y. J. Zhang, Angew. Chem.
Int. Ed. 2014, 53, 6439.

HIGHLIGHT
HIGHLIGHT
Breaking the cycle: The formation
of cyclic organic carbonates is well
studied, although reactions utilizing
these versatile precursors are
relatively limited. The conversions
highlighted here showcase the use
of these organic carbonates as
valuable synthetic precursors,
providing facile access to highpotential synthons with excellent
stereochemical control.

Prof. Dr. Arjan W. Kleij, Dr.
Christopher J. Whiteoak*
Page No. – Page No.
Diastereo- and Enantioselective
Valorization of Cyclic Organic
Carbonates