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COMMUNICATION
Highly Efficient Catalytic Formation of (Z)-1,4-But-2-ene Diols
using Water as a Nucleophile
Wusheng Guo,[a][b] Luis Martínez-Rodríguez,[a][b] Eddy Martin,[a] Eduardo C. Escudero-Adán[a] and Arjan
W. Kleij*[a][c]

Abstract: The first general catalytic and highly stereo-selective
formation of (Z)-1,4-but-2-ene diols is described from readily available
and modular vinyl-substituted cyclic carbonate precursors using water
as a nucleophilic reagent. These 1,4-diol scaffolds can be generally
prepared in high yields and with ample scope in reaction partners
using a simple synthetic protocol that does not require the presence
of any additive or any special precaution unlike the stoichiometric
approaches reported to date. Control experiments support the
mechanistic view that hyper-conjugation within the catalytic
intermediate after decarboxylation plays an imperative role to control
the stereo-selective outcome of these reactions.

Diols are among the most ubiquitous scaffolds in chemistry being
of eminent value to synthetic and polymer chemistry and typically
encompassing a wide structural diversity. [1] The stereoselective
and enantio-selective preparation of 1,2-diols has undoubtedly
received most of the attention of the synthetic community with the
development of the hydrolytic kinetic resolution of epoxides [2] and
the asymmetric cis-dihydroxylation of alkenes[3] representing
important milestones in this area. As established for 1,3-diols,[1a]
diastereo-selective preparation of other diol scaffolds remains
rewarding but persists to challenge synthetic chemists. In this
respect, acyclic unsaturated (Z)-configured 1,4-diols have found
important applications as transient scaffolds towards the stereocontrolled preparation of vinylcyclopropanes,[4] vinyl glycinols[5]
and the formation of lactones.[6] A recent contribution from
Hoveyda[7] has exposed further growth potential of these 1,4-diol
synthons in catalytic and stereoselective cross-metathesis
furnishing valuable acyclic (Z)-allylic alcohols.
Up to now, the limited amount of available strategies for (Z)1,4-but-2-ene diols synthesis have in common that they require
stoichiometric chemistry and/or air-sensitive reagents such as
DIBAL-H (diisobutylaluminum hydride).[4,5] Despite the increasing
incentive of (Z)-1,4-but-2-ene diols in synthetic chemistry, the
quest towards an efficient and mild catalytic protocol focusing on
such (substituted) 1,4-diol scaffolds still continues.[8] Inspired by
the dearth of catalytic solutions for the stereo-controlled

[a]

[b]
[c]

Dr. W. Guo, L. Martinez, Dr. E. Martin, E. C. Escudero-Adán, Prof.
Dr. A. W. Kleij, Institute of Chemical Research of Catalonia (ICIQ),
the Barcelona Institute of Science and Technology, Av. Països
Catalans 16, 43007 Tarragona, Spain
E-mail: akleij@iciq.es
These authors contributed equally.
Prof. Dr. A. W. Kleij
Catalan Institute of Research and Advanced Studies (ICREA), Pg.
Lluís Companys 23, 08010 Barcelona, Spain
Supporting information for this article is given via a link at the end of
the document

construction of substituted (Z)-but-2-ene diols, we anticipated the
use of vinyl-substituted cyclic carbonates as key reaction
partners. Previous success with these latter scaffolds
demonstrated that decarboxylative functionalization with suitable
electrophiles such as Michael acceptors is feasible under mild
reaction conditions giving access to furans,[9a] tertiary
vinylglycols[9b] and highly functional pyrrolidines. [9c] As an
intermediate in these Pd-mediated processes a zwitter-ionic
structure was postulated (see Scheme 1). Conceptually, such a
charged-separated structure should possess ambivalent
reactivity, with the Pd-allyl fragment being highly electrophilic and
amenable to react with (very) weak nucleophiles such as water.
Examples of catalytic conversions that are based on the use of
water as nucleophilic reagent are, however, extremely rare.[1f,2,10]
A successful development of new catalytic methodology towards
selective (Z)-but-2-ene diol formation by nucleophilic hydration of
in situ formed allyl surrogates would provide a highly attractive
new route towards these synthetically useful scaffolds. Here we
disclose such a conceptually new and highly efficient approach
for (Z)-but-2-ene diols that is based on a decarboxylative
hydration of readily available vinyl-based cyclic carbonates under
mild operating conditions (Scheme 1).

Scheme 1. A previously postulated zwitterionic Pd-allyl intermediate and
current approach towards (Z)-1,4-but-2-ene diols using H2O as nucleophile.

The screening phase towards appropriate reaction conditions
for the synthesis of unsaturated 1,4-diol compound 1 started off
with the use of vinyl carbonate A and using various Pd precursors
and phosphine ligands (Table 1). Various Pd precursors were
tested including the well-known and reactive White catalyst.[11] We
first screened various mono- and bidentate ligands (L1L8)
combined with this precursor using DMF as solvent.[12] Whereas
the use of mono-dentate phosphine ligands L1L5 (entries 15)
did not result in any observable formation, to our delight the
presence of bidentate phosphines L6L8 (entries 68) proved to
be highly beneficial for the formation of the desired 1,4-but-2-ene
diol 1 under ambient conditions (see also Table S1, Supporting

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Information). Moreover, 1H NMR analysis supported the exclusive
formation of the (Z)-configured product (Z/E >99:1). Further
screening (entries 9-13) of other Pd precursors in the presence of
L8 showed Pd(dba)2 and [Pd2(dba)3·CHCl3] (dba =
dibenzylideneacetone) to be competitive precursors, but to avoid
any potential problem related to the stability of these Pd
precursors we decided to continue with the air-stable White
precursor. Other solvents than DMF were probed (entries 1417)
but these showed inferior yields of 1 underlining the crucial
importance of the polarity of the medium.

selectivity (>99:1) towards the (Z) isomer were noted. This userfriendly procedure does not require any additive and can be
operated in air at ambient temperature. The introduction of
various aryl groups in the olefinic unit is tolerated including para,
meta- and ortho-substituted (di)halo-aryls (2, 3, 7, 18, 19, 20, 21,
23 and 24), benzoic ester (9) and even thioether (12) groups. The
use of 2- and 3-furyl, thiophene- and 3-pyridyl-substituted cyclic
carbonates smoothly leads to (Z)-1,4-diols 1316 in high yield
despite the potential of the heteroatoms to coordinate and
deactivate the Pd-catalyst.

Table 1. Optimization of conditions in the synthesis of (Z)-but-2ene diol 1 varying the Pd precursor, ligand L and solvent.[a]

Entry

Pd precursor

L

Solvent
[1M]

Yield[b][c]
[%]

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17

Pd/bis-sulfoxide
Pd/bis-sulfoxide
Pd/bis-sulfoxide
Pd/bis-sulfoxide
Pd/bis-sulfoxide
Pd/bis-sulfoxide
Pd/bis-sulfoxide
Pd/bis-sulfoxide
[Pd2(dba)3]CHCl3
Pd(dba)2
Pd(OAc)2
Pd/C
Pd(PPh3)2Cl2
Pd/bis-sulfoxide
Pd/bis-sulfoxide
Pd/bis-sulfoxide
Pd/bis-sulfoxide

L1
L2
L3
L4
L5
L6
L7
L8
L8
L8
L8
L8
L8
L8
L8
L8
L8

DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
MeOH
CH2Cl2
THF

0
0
0
0
0
90
95
98
97
99
94
0
70
40
<1
0
0

[a] Reaction conditions: 0.20 mmol of carbonate, 0.20 mL of solvent,
rt; [b] NMR yield using toluene as internal standard, see Supporting
Information for details. [c] In all cases the Z/E ratio was >99:1 as
determined by 1H NMR.

The optimized conditions reported in entry 8 of Table 1 were
then used to investigate the product scope in detail (Figure 1).
The Rgroups of the vinyl carbonate reagent was systematically
varied (for their preparation, see Supporting Information) and
provided an entry into a series of substituted (Z)-but-2-ene diols
128. In most cases excellent isolated yields (up to 98%) and

X-ray of 8

Figure 1. Product scope in the Pd-mediated formation of (Z)-but-2-ene diols 128. Substrate amounts used: carbonate (0.20 mmol), DMF (0.20 mL). The Z/E
ratios were determined by 1H NMR spectroscopy (CDCl3). Although following
the same stereo-chemical formation pathway, compound 15 has formally an (E)
configuration. [a] Using 5 mol% of Pd precursor and 10 mol% of L8, 60ºC, 200
L DMF, 60 L H2O.

Interestingly, the presence of other substitution patterns is also
allowed producing an -functionalized diol (27) and a tetrasubstituted olefin derivative (28). Generally, in order to prepare
these latter compounds with more elaborate substitutions and

COMMUNICATION
those incorporating ortho-functionalized aryl groups (cf., 20 and
21) and 3-pyridyl based 16 a higher reaction temperature and
additional water in the medium was required; for these more
challenging conversions also a higher amount of Pd catalyst (5
mol%) was necessary. The (Z) configuration was deduced from
1D and 2D NMR analysis, whereas in the case of 8 further
evidence for the preferred stereo-isomer formation was obtained
from X-ray diffraction studies (Figure 1).[13]

corresponding (Z)-but-2-ene diols, the synthesis of 3134 was
attempted under the optimized reaction conditions. When alkylsubstituted carbonates were probed (C; R = alkyl) no conversion
to the targeted diols 31 and 32 could be observed up to 60ºC.
Interestingly, diol 33 derived from carbonate D that incorporates
an additional vinyl substituent was obtained in 74% yield as a
72:28 mixture of both (Z) and (E) isomers. When carbonate E was
employed the corresponding diol 34 (Z/E = 1:1) was obtained
under even lower stereo-control.
From the results presented in Scheme 2 a mechanistic
rationale is proposed taking the previously postulated zwitter-ionic
Pd-allyl intermediate I[9] as starting point (Scheme 3). Equilibration
of 3-allyl-Pd species I to 1-palladacyclic intermediate II is
electronically biased as the presence of an aryl/vinyl substituent
allows for hyper-conjugation of the double bond: this in turn
controls the (Z) configuration of the palladacycle and thus the
stereo-control towards the 1,4-diol product. In turn, the lack of
reactivity towards diol formation when R is an alkyl group (cf., 31
and 32; scheme 2) is explained by a larger charge-delocalization
in intermediate I onto which nucleophilic attack by water is
disfavored for electronic reasons. Thus, clearly electron-donating
groups are unable to mediate the formation of intermediate II and
no conversion is observed as indeed noted experimentally.

Scheme 2. Control experiments using vinyl carbonates BE as substrates
under different conditions: (i) anhydrous DMF (0.2 mL), White catalyst (2.0
mol%), L8 (5.0 mol%), rt, 12 h; (ii) anhydrous DMF/H2O18 (0.2 mL; 9:1), White
catalyst (2.0 mol%), L8 (5.0 mol%), rt, 12 h; (iii) DMF/H2O, NaOH (5 eq), rt, 8 h.
(iv) conditions as under (i) using commercial DMF.

Intrigued by the highly stereo-selective nature of these
conversions and in order to gain mechanistic insight, we
performed a series of control experiments. Vinyl carbonate B
(Scheme 2) was subjected to the same reaction conditions as
used for 128 using anhydrous DMF; no conversion to diol (Z)-8
could be noted. Using a combination of anhydrous DMF with 18Olabelled water (9:1 v/v) and treatment of vinyl carbonate B under
these conditions afforded the labelled diol (Z)-29 in 62% yield:
these combined results support the key role of water in the stereoselective formation of the 1,4-diols. Further to this, when
carbonate B is treated with H2O under basic conditions in the
absence of Pd catalyst the 1,2-diol 30 is produced that results
from the hydrolysis of the carbonate unit.[3c,14] Therefore, the
presence of a suitable Pd catalyst is essential to produce the 1,4diol products. In order to examine whether other vinyl-substituted
carbonates (i.e., CE) would equally convert to their

Scheme 3. Proposed mechanistic manifolds related to the Pd intermediates
formed after decarboxylation.

Scheme 4. Examples of post-use of (Z)-1,4-but-2-ene diol 1 in the synthesis of
other interesting scaffolds (3537). Conditions/reagents used: (i) NaH (3 eq.),
MeI (4 eq.), DMF, rt; then m-CPBA (1.1 eq.), DCM, rt, 18 h; (ii) CuI (5 mol%),
2,2´-bipy (5 mol%), 9-azabicyclo[3.3.1]nonane N-oxyl (1 mol%), N-methyl
imidazole (10 mol%), ACN, rt, 3 h; (iii) Camphorsulfonic acid (1 mol%), trimethyl
orthoformate (2 eq.), DCM, rt, 5 h.

COMMUNICATION
In the case of the non-substituted carbonate E (Scheme 2),
relatively slower conversion towards diol product is observed. The
low Z/E ratio of this latter conversion is the result of a nonstereospecific nucleophilic attack governed by steric rather than
electronic considerations.
Finally, the post-modification potential of these (Z)-1,4-but-2ene diols was investigated using 1 as starting material (Scheme
4). Simple oxidation of the double bond (after alcohol protection)
in 1 by meta-chloroperoxybenzoic acid afforded 35 as a single
diastereo-isomer in 77% yield. Oxidative lactonization of 1 using
a radical initiator (9-azabicyclo[3.3.1]nonane N-oxyl) under Cucatalysis in the presence of N-methyl-imidazole produced the
lactone 36 in 97% yield.[6] The cyclic ortho-ester 37 was prepared
by combining 1 with trimethyl orthoformate[4] under acid catalysis
providing a well-known protection of this diol useful in synthetic
chemistry.[15]
In summary, we here describe a user-friendly, highly mild and
stereo-selective methodology towards the formation of
synthetically useful (Z)-1,4-but-2-ene diols in high yield and under
exclusive stereo-control. This procedure utilizes readily available
and modular vinyl-based cyclic carbonates and simple water as
reactants, can be operated in air and does not require any additive.
Such privileged conditions may greatly advance the use of these
diol synthons in preparative chemistry as demonstrated herein.

[2]
[3]

[4]
[5]
[6]
[7]
[8]

[9]

[10]

Acknowledgements
We thank ICIQ, ICREA, and the Spanish Ministerio de Economía
y Competitividad (MINECO) through project CTQ-2014–60419-R,
and the Severo Ochoa Excellence Accreditation 2014–2018
through project SEV-2013–0319. Dr. Noemí Cabello, Sofía Arnal,
and Vanessa Martínez are acknowledged for the mass analyses.
WG thanks the Cellex foundation for funding of a postdoctoral
fellowship.
Keywords: decarboxylative functionalization • homogeneous
catalysis • palladium • stereoselectivity • (Z)-1,4-but-2-ene diols
[1]

a) E. Bode, M. Wolberg, M. Müller, Synthesis 2006, 557-558; b) H. C.
Kolb, M. S. VanNieuwenhuize, K. B. Sharpless, Chem. Rev. 1994, 94,
2483-2547; c) H. R. Kricheldorf, J. Macromol. Sci., Part C: Polym. Rev.
1997, 37, 599-631; d) C. J. R. Bataille, T. J. Donohoe, Chem. Soc. Rev.
2011, 40, 114-128; Use of diols for polyurethane preparations: e) H.-W.
Engels, H.-G. Pirkl, R. Albers, R. W. Albach, J. Krause, A. Hoffmann, H.
Casselmann, J. Dormish, Angew. Chem. Int. Ed. 2013, 52, 9422–9441;
In hydrolytic kinetic resolution: f) E. N. Jacobsen, Acc. Chem. Res. 2000,
33, 421-431.

[11]

[12]
[13]
[14]

[15]

M. Tokunaga, J. F. Larrow, F. Kakiuchi, E. N. Jacobsen, Science 1997,
277, 936-938.
a) E. N. Jacobsen, I. Marko, W. S. Mungall, G. Schroeder, K. B.
Sharpless, J. Am. Chem. Soc. 1988, 110, 1968-1970; b) H. C. Kolb, P.
G. Anderson, K. B. Sharpless, J. Am. Chem. Soc. 1994, 116, 1278-1291.
For a recent diastereo-selective approach towards syn-diols from cyclic
carbonate precursors see: c) V. Laserna, G. Fiorani, C. J. Whiteoak, E.
Martin, E. Escudero-Adán, A. W. Kleij, Angew. Chem. Int. Ed. 2014, 53,
10416-10419.
D. Craig, S. J. Gore, M. I. Lansdell, S. E. Lewis, A. V. W. Mayweg, A. J.
P. White, Chem. Commun. 2010, 46, 4991-4993.
K. Klimovica, L. Grigorjeva, A. Maleckis, J. Popelis, A. Jirgensons,
Synlett. 2011, 2849-2851.
X. Xie, S. S. Stahl, J. Am. Chem. Soc. 2015, 137, 3767-3770.
M. J. Koh, R. K. M. Khan, S. Torker, M. Yu, M. S. Mikus, A. H. Hoveyda,
Nature 2015, 517, 181-186.
The only known catalytic method towards (Z)-but-2-ene diols (only 1
example) is based on the Pd-mediated hydroarylation of alkynes using
arylboronic acids at 80ºC in 1,4-dioxane, see: a) C. H. Oh, H. H. Jung, K.
S. Kim, N. Kim, Angew. Chem. Int. Ed. 2003, 42, 805-808; b) A. K. Gupta,
K. S. Kim; C. H. Oh, Synlett. 2005, 457-460.
a) A. Khan, L. Yang, J. Xu, L. Y. Jin, Y. J. Zhang, Angew. Chem. Int. Ed.
2014, 53, 11257-11260; b) A. Khan, R. Zheng, Y. Kan, J. Ye, J. Xing, Y.
J. Zhang, Angew. Chem. Int. Ed. 2014, 53, 6439-6442; c) K. Ohmatsu,
N. Imagawa, T. Ooi, Nat. Chem. 2014, 6, 47-51.
a) G. Dong, P. Teo, Z. K. Wickens, R. H. Grubbs, Science 2011, 333,
1609-1612; b) Q.-K. Kang, L. Wang, Q.-J. Liu, J.-F. Li, Y. Tang. J. Am.
Chem. Soc. 2015, 137, 14594-14597; Recently Sanford reported the in
situ nucleophilic substitution of an alkyl chloride by water in the siteselective CH oxidation of amines at 150ºC, see: c) M. Lee, M. S.
Sanford, J. Am. Chem. Soc. 2015, 137, 12796-12799. For related allylic
hydroxylation see: d) B. J. Lüssem, H. J. Gais, J. Am. Chem. Soc. 2003,
125, 6066-6067; e) N. Kanbayashi, K. Onitsuka, Angew. Chem. Int. Ed.
2011, 50, 5197-5199; f) M. Gärtner, S. Mader, K. Seehafer, G. Helmchen,
J. Am. Chem. Soc. 2011, 133, 2072-2075.
The White catalyst is a bis-sulfoxide ligated Pd(OAc)2 precursor that has
shown high potential in various allylic conversions, see for instance: a)
C. C. Pattillo, I. I. Strambeanu, P. Calleja, N. A. Vermeulen, T. Mizuno,
M. C. White, J. Am. Chem. Soc. 2016, 138, 1265-1272; b) E. M. Stang,
M. C. White, Nat. Chem. 2009, 1, 547-551.
Note that if larger excess of H2O was used, the reaction was completely
shut down.
For more details see: CCDC-1465246.
Simple hydrolysis of cyclic carbonates towards 1,2-diols has been welldocumented, see for instance: a) P. Le Gendre, T. Braun, C. Bruneau, P.
H. Dixneuf, J. Org. Chem. 1996, 61, 8453-8455; b) C. Beattie, M. North,
P. Villuendas, C. Young, J. Org. Chem. 2013, 78, 419-426; c) S. Sarel, I.
Levin, L. A. Pohoryles, J. Chem. Soc. 1960, 3079-3082. See also
reference 3c.
a) M. Sekine, T, Hata, J. Am. Chem. Soc. 1983, 105, 2044-2049; b) J. J.
Bozell, D. Miller, B. R. Hames, C.Loveless, J. Org. Chem. 2001, 66,
3084-3089.

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Entry for the Table of Contents

COMMUNICATION
A highly efficient and stereoselective Pd-mediated
synthesis of substituted (Z)1,4-diols is described using
allyl surrogates derived from
vinyl cyclic carbonates. The
methodology is characterized
by its operational simplicity,
high yields and stereo-control
using water as a nucleophilic
reagent. Control experiments
support the view that hyperconjugation plays an
imperative role in these stereospecific conversions.

Wusheng Guo, Luis MartínezRodríguez, Eddy Martin, Eduardo
C. Escudero-Adán and Arjan W.
Kleij*

Page No. – Page No.

Highly Efficient Catalytic
Formation of (Z)-1,4-But-2-ene
Diols using Water as a
Nucleophile