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

Article abstract of DOI:10.1002/anie.201603638

The first general catalytic and highly stereoselective 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 method 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 hyperconjugation within the catalytic intermediate after decarboxylation plays an imperative role to control the stereoselective outcome of these reactions.

Full text of DOI:10.1002/anie.201603638

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201603638
German Edition: DOI: 10.1002/ange.201603638
Homogeneous Catalysis
Highly Efficient Catalytic Formation of (Z)-1,4-But-2-ene Diols using
Water as a Nucleophile
Wusheng Guo+, Luis Martꢀnez-Rodrꢀguez+, Eddy Martin, Eduardo C. Escudero-Adꢁn, and
Arjan W. Kleij*
Abstract: The first general catalytic and highly stereoselective
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
method 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 hyperconjugation within the catalytic intermediate
after decarboxylation plays an imperative role to control the
stereoselective outcome of these reactions.
chemistry, the quest towards an efficient and mild catalytic
procedure focusing on such (substituted) 1,4-diol scaffolds
still continues.[8] Inspired by the dearth of catalytic solutions
for the stereocontrolled 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[9] is feasible under mild reaction conditions giving
access to furans,[9a] tertiary vinylglycols,[9b] and highly func-
tional pyrrolidines.[9c] As an intermediate in these Pd-medi-
ated processes
a zwitterionic structure was postulated
(Scheme 1). Conceptually, such a charged-separated structure
D
iols 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 enantioselective 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] being important milestones in
this area. Although established for 1,3-diols,[1a] diastereose-
lective preparation of other diol scaffolds still remains
a challenge to synthetic chemists. In this respect, acyclic
unsaturated (Z)-configured 1,4-diols have found important
applications as transient scaffolds towards the stereocon-
trolled 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.
Scheme 1. A previously postulated zwitterionic Pd-allyl intermediate
and current approach towards (Z)-1,4-but-2-ene diols using H2O as
nucleophile.
should possess ambivalent reactivity, with the Pd-allyl frag-
ment 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 a new catalytic method towards selective
(Z)-but-2-ene diol formation by nucleophilic hydration of
allyl surrogates formed in situ would provide a highly attrac-
tive new route towards these synthetically useful scaffolds.
Herein 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).
The screening phase towards appropriate reaction con-
ditions 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).
Several 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-
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
[*] Dr. W. Guo,[+] L. Martꢀnez-Rodrꢀguez,[+] Dr. E. Martin,
E. C. Escudero-Adꢁn, Prof. Dr. A. W. Kleij
Institute of Chemical Research of Catalonia (ICIQ)
The Barcelona Institute of Science and Technology
Av. Paꢂsos Catalans 16, 43007 Tarragona (Spain)
E-mail: akleij@iciq.es
Prof. Dr. A. W. Kleij
Catalan Institute of Research and Advanced Studies (ICREA)
Pg. Lluꢀs Companys 23, 08010 Barcelona (Spain)
[+] These authors contributed equally to this work.
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under
http://dx.doi.org/10.1002/anie.201603638.
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Table 1: Optimization of conditions in the synthesis of (Z)-but-2-ene diol
1 varying the Pd precursor, ligand L, and solvent.[a]
1 underlining the crucial importance of the polarity of the
medium.
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 were
systematically varied (for their preparation, see the Support-
ing Information) and provided a series of substituted (Z)-but-
2-ene diols 1–28. In most cases excellent yields of isolated
product (up to 98%) and selectivity (> 99:1) towards the (Z)
isomer were noted. This user-friendly 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, 18–21, 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
Entry
Pd precursor
L
Solvent
[1 m]
Yield[b,c]
[%]
1
2
3
4
5
6
7
8
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
9
10
11
12
13
14
15
16
17
0
[a] Reaction conditions: 0.20 mmol of carbonate, 0.20 mL of solvent, rt.
[b] NMR yield using toluene as internal standard; see the Supporting
Information for details. [c] In all cases, the Z/E ratio was >99:1 as
1
determined by H NMR spectroscopy.
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 the Supporting Infor-
mation, Table S1). 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 catalyst precursor. Other solvents than DMF were
probed (entries 14–17) but these showed inferior yields of
Figure 1. Product scope in the Pd-mediated formation of (Z)-but-2-ene
diols 1–28. 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 stereochemical formation path-
way, compound 15 has formally an (E) configuration. [a] Using
5 mol% of Pd precursor and 10 mol% of L8, 608C, 200 mL DMF, 60 mL
H2O.
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potential of the heteroatoms to coordinate and deactivate the
Pd catalyst.
Interestingly, the presence of other substitution patterns is
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 1,4-diol products. To examine
whether other vinyl-substituted carbonates (that is, C–E)
would equally convert into their corresponding (Z)-but-2-ene
diols, the synthesis of 31–34 was attempted under the
optimized reaction conditions. When alkyl-substituted carbo-
nates were probed (C; R = alkyl) no conversion into the
targeted diols 31 and 32 could be observed up to 608C.
Interestingly, diol 33 derived from carbonate D that incorpo-
rates 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 stereocontrol.
also allowed, producing an a-functionalized diol (27) and
a tetra-substituted olefin derivative (28). Generally, to
prepare these latter compounds with more elaborate sub-
stitutions and 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 a higher
amount of Pd catalyst (5 mol%) was also necessary. The (Z)
configuration was deduced from 1D and 2D NMR analysis,
whereas in the case of 8 further evidence for the preferred
stereoisomer formation was obtained from X-ray diffraction
studies (Figure 1).[13]
Intrigued by the highly stereoselective nature of these
conversions and 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 into diol (Z)-8 could be
noted. Using a combination of anhydrous DMF with 18O-
labeled water (9:1 v/v) and treatment of vinyl carbonate B
under these conditions afforded the labeled 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
From the results presented in Scheme 2, a mechanistic
rationale is proposed taking the previously postulated zwit-
terionic Pd-allyl intermediate I[9] as starting point (Scheme 3).
Scheme 3. Proposed mechanistic manifolds related to the Pd inter-
mediates formed after decarboxylation.
Equilibration of h3-allyl-Pd species I to h1-palladacyclic
intermediate II is electronically biased, as the presence of
an aryl/vinyl substituent allows for hyperconjugation of the
double bond: this in turn controls the (Z) configuration of the
palladacycle and thus the stereocontrol towards the 1,4-diol
product. In turn, the lack of reactivity towards diol formation
when R is an alkyl group (compare 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 was indeed noted experimentally.
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 non-stereospecific nucleophilic attack governed by
steric rather than electronic considerations.
Finally, the post-modification potential of these (Z)-1,4-
but-2-ene 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 diastereoisomer in 77% yield.
Oxidative lactonization of 1 using a radical initiator (9-
azabicyclo[3.3.1]nonane N-oxyl) under Cu catalysis 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
Scheme 2. Control experiments using vinyl carbonates B–E as sub-
strates under different conditions: i) anhydrous DMF (0.2 mL), White
catalyst (2.0 mol%), L8 (5.0 mol%), rt, 12 h; ii) anhydrous DMF/H218O
(0.2 mL; 9:1), White catalyst (2.0 mol%), L8 (5.0 mol%), rt, 12 h;
iii) DMF/H2O, NaOH (5 equiv), rt, 8 h; iv) conditions as under (i) but
using commercial DMF.
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Kolb, P. G. Anderson, K. B. Sharpless, J. Am. Chem. Soc. 1994,
116, 1278 – 1291; For recent diastereoselective approach
a
towards syn-diols from cyclic carbonate precursors see: c) V.
Laserna, G. Fiorani, C. J. Whiteoak, E. Martin, E. Escudero-
Adꢂn, A. W. Kleij, Angew. Chem. Int. Ed. 2014, 53, 10416 –
10419; Angew. Chem. 2014, 126, 10584 – 10587.
[4] 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.
[5] K. Klimovica, L. Grigorjeva, A. Maleckis, J. Popelis, A.
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[6] X. Xie, S. S. Stahl, J. Am. Chem. Soc. 2015, 137, 3767 – 3770.
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Hoveyda, Nature 2015, 517, 181 – 186.
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 equiv.), MeI (4 equiv.), DMF, rt; then m-CPBA
(1.1 equiv.), 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%), MeCN, rt, 3 h; iii) Camphorsulfonic acid (1 mol%), tri-
methyl orthoformate (2 equiv.), DCM, rt, 5 h.
[8] The only known catalytic method towards (Z)-but-2-ene diols
(only one example) is based on the Pd-mediated hydroarylation
of alkynes using arylboronic acids at 808C 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; Angew. Chem. 2003, 115, 829 – 832;
b) A. K. Gupta, K. S. Kim, C. H. Oh, Synlett 2005, 457 – 460.
[9] a) A. Khan, L. Yang, J. Xu, L. Y. Jin, Y. J. Zhang, Angew. Chem.
Int. Ed. 2014, 53, 11257 – 11260; Angew. Chem. 2014, 126, 11439 –
11442; b) A. Khan, R. Zheng, Y. Kan, J. Ye, J. Xing, Y. J. Zhang,
Angew. Chem. Int. Ed. 2014, 53, 6439 – 6442; Angew. Chem.
2014, 126, 6557 – 6560; c) K. Ohmatsu, N. Imagawa, T. Ooi, Nat.
Chem. 2014, 6, 47 – 51; For other recent relevant examples see:
d) A. Khan, J. Xing, J. Zhao, Y. Kan, W. Zhang, Y. J. Zhang,
Chem. Eur. J. 2015, 21, 120 – 124; e) L. Yang, A. Khan, R. Zheng,
L. Y. Jin, Y. J. Zhang, Org. Lett. 2015, 17, 6230 – 6233; f) A.
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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 stereoselective method towards the formation of syn-
thetically useful (Z)-1,4-but-2-ene diols in high yield and
under exclusive stereocontrol. 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.
[10] 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
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À
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Acknowledgements
We thank ICIQ, ICREA, and the Spanish Ministerio de
Economꢀa y Competitividad (MINECO) through project
CTQ-2014-60419-R, and the Severo Ochoa Excellence
Accreditation 2014–2018 through project SEV-2013-0319.
Dr. Noemꢀ Cabello, Sofꢀa Arnal, and Vanessa Martꢀnez are
acknowledged for the mass analyses. W.G. thanks the Cellex
foundation for funding of a postdoctoral fellowship.
[11] The White catalyst is a bis(sulfoxide) ligated Pd(OAc)2 pre-
cursor that has shown high potential in various allylic conver-
sions; see for example: 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.
[12] Note that if larger excess of H2O was used, the reaction was
completely shut down.
[13] CCDC 1465246 contains the supplementary crystallographic
data for this paper. These data are provided free of charge by
The Cambridge Crystallographic Data Centre.
Keywords: But-2-ene diols · decarboxylative functionalization ·
homogeneous catalysis · palladium · stereoselectivity
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Revised: June 21, 2016
Published online: && &&, &&&&
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Communications
Homogeneous Catalysis
A highly efficient and stereoselective Pd-
mediated synthesis of substituted (Z)-
1,4-diols is described using allyl surro-
gates derived from vinyl cyclic carbo-
nates. The method features operational
simplicity, high yields, and stereocontrol
using water as a nucleophilic reagent.
Control experiments support the view
that hyperconjugation plays an impera-
tive role in these stereospecific conver-
sions.
W. Guo, L. Martꢁnez-Rodrꢁguez, E. Martin,
E. C. Escudero-Adꢂn,
A. W. Kleij*
&&&& — &&&&
Highly Efficient Catalytic Formation of
(Z)-1,4-But-2-ene Diols using Water as
a Nucleophile
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These are not the final page numbers!