Gold-catalyzed reactions of propargylic esters with vinylazides for the synthesis of Z- or E-configured buta-1,3-dien-2-yl esters

Article abstract of DOI:10.1039/c5cc05945c

Gold-catalyzed synthesis of buta-1,3-dien-2-yl esters by the reaction of propargyl esters with vinylazides is described; the reaction mechanism is postulated to involve a vinyl attack of vinylazides at alkenyl gold carbenes.

Full text of DOI:10.1039/c5cc05945c

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: R. Liu and S. B.
Wagh, Chem. Commun., 2015, DOI: 10.1039/C5CC05945C.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/chemcomm

View Article Online
DOI: 10.1039/C5CC05945C
Page 1 of 5
ChemComm
Journal Name
RSCPublishing
COMMUNICATION
Gold-catalyzed Reactions of Propargylic Esters
with Vinylazides for the Synthesis of Z- or E-
configured Buta-1,3-dien-2-yl esters
Cite this: DOI:
10.1039/x0xx00000x
Sachin Bhausaheb Wagh and Rai-Shung Liu*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
Gold-catalyzed synthesis of buta-1,3-dien-2-
yl esters from including Au(I)-catalyzed rearrangement of propargylic esters5
the reactions of propargyl esters and vinylazides are (eq 1) and gold and rhodium-catalyzed rearrangement of allenyl
described; the reaction mechanism is postulated to involve a esters (eq 2).6 Dixneuf et al. recently reported ruthenium-
vinyl attack of vinylazides at alkenyl gold carbenes.
catalyzed reactions of propargylic esters with diazoalkanes to
form buta-1,3-dien-2-yl esters (eq 3).7 In this work, we report
Buta-1,3-dien-2-yl esters are useful four-carbon building units gold-catalyzed reactions of propargylic esters with vinylazides,8
in Diels-Alder reactions,1 which are powerful tools to access to form Z- or E-configured buta-1,3-dien-2-yl esters and nitriles.
complicated naturally occurring alkaloids.2 These species serve This process has mechanistic interest because the C=C bonds of
also as reagents for the synthesis of monofluoroalkyl α,β- vinylazides become cleaved with the resulting =CH2 fragment
unsaturated ketones.3 They are accessible also to various chiral adding to the terminal alkynyl carbons of propargyl esters. The
molecules through asymmetric hydrogenations4a and enantio- control of the Z and E configurations of resulting buta-1,3-dien-
selective allylation reaction.4b Convenient syntheses of buta- 2-yl esters is also discussed.
1,3-dien-2-yl esters rely on transition metal-catalyzed reactions
Table 1. Catalyst screening for the formation buta-1,3-dien-2-yl esters
Department of Chemistry, National Tsing Hua University 101, Sec. 2, Kuang-Fu Rd.,
Hsinchu, 30013 (Taiwan) E-mail: rsliu@mx.nthu.edu.tw
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
a1a (0.191 M, 1.0 equiv), 2a (2.0 equiv), bProduct yields are given after
purification from a silica column, IPr = 1,3-bis(diisopropyl phenyl)
imidazol-2-ylidene, L = P(t-Bu)2(o-biphenyl), nd = not determined.
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 1

View Article Online
ChemComm
DOI: 10.1039/C5CC05P94a5gCe 2 of 5
COMMUNICATION
Journal Name
Table 1 shows the optimization of reactions between
propargyl ester 1a and vinylazide 2a using various gold
catalysts. Our test with various gold catalysts (entries 1-4)
revealed that electron-rich and bulky LAuCl/AgSbF6 [L = P(t-
Table 3. Gold-catalyzed reaction of various propargyl esters with vinylazide
Bu)2(o-biphenyl)] and IPrAuCl/AgSbF6 (IPr
=
1,3-
bis(diisopropylphenyl)imidazole-2-ylidene) were efficient to
yield buta-1,3-dien-2-yl ester 3a in 67% and 63% yields
respectively, with complete consumption of initial 1a. We
identified the presence of benzonitrile in entry 2 through GC-
1
MS; its yield was estimated by H NMR of crude products.
Other solvents including toluene, nitromethane and THF, were
all ineffective, giving product 3a in negligible proportion
(entries 5-7). AgSbF6 alone was catalytically inactive, giving
unreacted 1a in 95% recovery (entry 8). Compound 3a has a Z-
configuration according to its 1H NOE spectra.9
We assessed the reactions using α-aryl vinylazides 2b-d (2.0
equiv) bearing various substituents (X = t-Bu, Cl, OMe) and
propargyl ester 1b (1.0 equiv). The reactions were performed
with P(t-Bu)2(o-biphenyl)AuCl/AgSbF6 (10 mol%) in hot DCE
(80 °C) for 24 h to allow complete conversion. In entries 1-3
(Table 2), the yields of desired buta-1,3-dien-2-yl ester 3b were
33%-63% with p-methoxyphenyl being the least efficient
because of its high basicity.
To explore the reaction mechanism, we carried out the
reactions on propargyl esters 1b-1p bearing various substituents.
Table 3 shows their reactions with model vinylazide 2a with
P(t-Bu)2(o-biphenyl)AuCl/AgSbF6 (10 mol %) in hot DCE (80
°C) for 12-24 h
configurations of resulting products, except compounds 3l
(R1 = R2). Buta-1,3-dien-2 yl esters 3b
3i have Z-configurations
(R2 = H, Z/E > 30:1) whereas products 3j
3k and 3o 3p bear E-
.
1H NOE spectra were recorded to elucidate the
-
3m
a1 (0.141 M, 1.0 equiv), 2a (2.0 equiv), bProduct yields are given after
purification from a silica column, L = P(t-Bu)2(o-biphenyl).
-
-
-
configurations (E/Z > 30:1). Various carboxylates (X = Ph and
t-Bu) maintained the reaction efficiency, which were known to
active for 1,2-carboxylate shifts10-11 (entries 1-2). Among
propargyl esters 1d-g bearing various 4-phenyl substituents
(entries 3-6), electron-rich phenyl groups (Me or OMe)
provided better product yields (82-84%) than their electron-
deficient analogues 3f and 3g (Cl, Br; 56-66%). This trend
reflects the relative ease of a 1,2-benzoyloxy shift.10-11 The
molecular structure of compound 3e was confirmed by X-ray
diffraction study.12 Electron-rich 2-furyl and 3-thienyl-derived
substrates 1g and 1h resulted in 60-68% yields as their small
sizes were not favorable for a 1,2-benzoyloxy shift (entries 7-8).
We tested the reactions on alkenyl and alkynyl substituents 1j
and 1k, preceding to desired products 3j and 3k in 61% and
74% respectively, albeit in E-configurations (E/Z > 30:1, entries
9-10). 3,3-Disubstituted propargyl esters 1l-1p were very
favorable for this benzoyloxy shift,10-11 delivering desired 3l-3p
in 72-80% yields (entries 11-15). In Table 3, the substituent
effects of propargyl esters enable us to conclude that 1,2-
carboxylate shifts affect the reaction efficiency whereas distinct
Z- and E-regioselectivities deserve mechanistic consideration.
Eq 5 shows that the transformation of buta-1,3-dien-2-yl
Table 2. Gold-catalyzed reaction of various vinylazides with propargyl ester
ester 3k into 4-benzylidene cyclopent-3-en-1-one
by P(t-Bu)2(o-biphenyl)AuCl/AgSbF6 (5 mol %) in DCE (60 °C,
20 h); the resulting product was present as E/Z regioisomers
(E:Z = 4:1) with a combined 90% yield. Compound was not
5 catalyzed
5
5
observed in the course of the formation of buta-1,3-dien-2-yl
ester 3k (Table 3, entry 10) because vinylazides likely reduce
the acidity of gold catalysts. Vinylazides can undergo thermal
rearrangement to 2H-azirines at elevated temperatures.8
a1b (0.141 M, 1.0 equiv), 2 (2.0 equiv), bProduct yields are given after
purification from a silica column, L = P(t-Bu)2(o-biphenyl).
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

View Article Online
DOI: 10.1039/C5CC05945C
Page 3 of 5
Journal Name
ChemComm
COMMUNICATION
2H-Azirine 6a was prepared from vinylazide 2a to examine its are less stable than their Z-isomers by 1.65 kcal/mol and 0.59
chemical reactivity. Under optimized condition, a mixture of kcal/mol respectively; the corresponding Z/E ratios are 16.6:1
propargyl ester 1b and 2H-azirine 6a with P(t-Bu)2(o- and 2.9:1 for species 3j and 3k respectively. This information
biphenyl)AuCl/AgSbF6 (10 mol %) in DCE (80 °C, 16 h), reveals that the formation of E-configured 3j and 3k are not
produced undesired dimeric product 6b13 with starting 1b in thermodynamically controlled, but the E-form of buta-1,3-dien-
80% recovery (eq 6)
. This observation precludes the 2-yl ester 3o is more stable than its Z-isomer by 1.45 kcal/mol
involvement of 2H-azirine 6a in our reaction system.
in DCE, corresponding to a E/Z ratio of 8.2.
For alkynyl- and alkenyl- substituted propargyl esters 1j-1k
we postulate that their initial gold carbenes C’ have a π-bond
motif cis to gold to attain a remote interaction, thus giving E-
configured products 3j-3k exclusively. For 3,3-disubstituted
propargyl esters 1o-1p, their initial Z-configured isomers
become catalyzed with Brønsted acid LAu(OH2)+ in hot DCE
(80 °C) to give thermodynamically favourable E-configured
,
products because their corresponding intermediates
tertiary carbocations.
F are stable
We propose a mechanism to rationalize the formation of Z-
and E-configured buta-1,3-dien-2-yl esters, as depicted in
Scheme 1 For most propargylic esters 1a-1i a gold-catalyzed
In summary, gold catalyzed synthesis of buta-1,3-dien-2-yl
esters from propargyl esters and vinylazides is described; the
utility of these reactions is manifested by their applicability
toward propargyl esters over a reasonable range. We postulate a
mechanism involving an initial 1,2-carboxylate shift of
propargylic esters to form gold-carbenes that are subjected to
the attack of vinylazides at the C-regioselectivity. This
mechanism predicts Z-configured buta-1,3-dien-2-yl esters to
be generated under kinetic control. Under the reaction
conditions, some Z-configured esters were catalyzed with either
gold-coordination or Brønsted acid-isomerization to form E-
isomers.
1,2-carboxylate shift10-11 is expected to form gold carbenes
C
that has preferably hydrogen cis to gold fragments to minimize
steric hindrance. Although a vinylazide might attack at an
electrophile at the nitrogen centers,8 such a regioselectivity fails
to rationalize the resulting buta-1,3-dien-2-yl ester. Instead, a
vinyl attack of vinylazide 2a at gold carbenes
C is expected to
form intermediate that subsequently undergoes a loss of N2,
D
further inducing a cleavage of the single CH2-CPh bond and the
elimination of a gold fragment. This mechanism rationalizes
most resulting products including 3a-3i (R2 = H) which have Z-
configurations.
Notes and references
We performed DFT-calculations (B3LYP/6-31G*) of buta-
1,3-dien-2-yl esters 3j-3k and 3o-3p to understand the relative
energies of their Z/E isomers in DCE; the data were provided in
Supporting Information (Table S1). For alkenyl and alkynyl-
derived products 3j and 3k, their resulting E-isomeric products
1
(a) D. Chen, X. Chen, Z. Lu, H. Cai, J. Shen, and G. Zhu, Adv. Synth.
Catal., 2011, 353, 1474; (b) J. E. Rainbolt, and G. P. Miller, J. Org.
Chem., 2007, 72, 3020; (c) K. Miki, K. Ohe, and S. Uemura, J. Org.
Chem., 2003, 68, 8505; (d) H. Tanaka, A. Kosaka, S. Yamashita, K.
Morisaki, and S. Torii, Tetrahedron. Lett., 1989, 30, 1261.
T. B. Dunn, J. M. Ellis, C. C. Kofink, J. R. Manning, and L. E.
Overman, Org. Lett., 2009, 11, 5658.
2
3
4
5
Z. Jin, R. S. Hidinger, B. Xu, and G. B. Hammond, J. Org. Chem.,
2012, 77, 7725.
(a) N. W. Boaz, Tetrahedron. Lett., 1998, 39, 5505; (b) D. C. Behenna,
and B. M, Stoltz, J. Am. Chem. Soc., 2004, 126, 15044.
(a) S. Wang, and L. Zhang, Org. Lett., 2006, 8, 4585; (b) G. Li, G.
Zhang, and L. Zhang, J. Am. Chem. Soc., 2008, 130, 3740; (c) Y.
Wang, B. Lu, and L. Zhang, Chem. Commun., 2010, 46, 9179.
6
7
8
(a) A. K. Buzas, F. M. Istrate, and F. Gagosz, Org. Lett., 2007,
(b) X. Zhang, C. Fu, and S. Ma, Org. Lett., 2011, 13, 1920.
9, 985;
C. V. L. Bray, S. Derien, and P. H. Dixneuf, Angew. Chem. Int. Ed.,
2009, 48, 1439.
For catalytic reactions of vinylazides with alkynes, see: (a) S. Chiba,
Synlett, 2012, 23, 21; (b) Y. Wang, K. K. Toh, J. Y. Lee, and S.
Chiba, Angew. Chem. Int. Ed., 2011, 50, 5927; (c) Y. F. Wang, and S.
Chiba, J. Am. Chem. Soc., 2009, 131, 12570; (d) N. S. Loy. A. Singh,
X. Xu, and C. H. Park, Angew. Chem. Int. Ed., 2013, 52, 2212; (d) L.
Zhu, Y. Yu, Z. Mao, X. Haung, Org. Lett., 2015, 17, 30; (e) S. K.
Scheme 1 A plausible mechanism.
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 3

View Article Online
ChemComm
DOI: 10.1039/C5CC05P94a5gCe 4 of 5
COMMUNICATION
Journal Name
Pawar, R. L. Sahani and R. S. Liu, Chem. Eur. J., 2015, 21, DOI:
10.1002/Chem.201500694.
9
1H NOE Spectroscopic data of key compounds are provided in the
Supporting Information (ESI).
10 See selected reviews: (a) A. Furstner and P. W. Davies, Angew. Chem.
Int. Ed., 2007, 46, 3410; (b) A. Arcadi, Chem. Rev., 2008, 108, 3266;
(c) A. S. K. Hashmi, Chem. Rev., 2007, 107, 3180; (d) Z. Li, C.
Brouwer, and C. He, Chem.Rev., 2008, 108, 3239; (e) D. Grorin, B.
D. Sherry, and F. D. Toste, Chem. Rev., 2008, 108, 3351.
11 (a) C. Zhao, X. Xie, S. Duan, H. Li, R. Fang and X. She, Angew.
Chem. Int. Ed., 2014, 53, 10789; (b) J. Liu, M. Chen, L. Zhang and Y.
Liu, Chem. Eur. J., 2015, 21, 1009; (c) C. H. M. Amijs, V. L, Carrillo
and A. M. Echavarren, Org. Lett., 2007, 9, 4021; (d) G. Li, G. Zhang,
and L. Zhang, J. Am. Chem. Soc., 2008, 130, 3740; (e) N. Marion, S.
D. Gonzalez, P. D. Fremont, A. R. Noble and S. P. Nolan, Angew.
Chem. Int. Ed., 2006, 45, 3647.
12 The crystallographic data of compound 3e were provided in ESI;
these data were also deposited at Cambridge Crystallographic data
Center (CCDC 1412097). These data can be obtained free of charge
from the CCDC via www.ccdc.cam.ac.uk/data_request/cif.
13 M. Nitta and T. Kobayashi, Chem. Lett. 1983, 1715.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

View Article Online
DOI: 10.1039/C5CC05945C
Page 5 of 5
ChemComm
Journal Name
COMMUNICATION
Gold-catalyzed Reactions of Propargylic
Esters with Vinylazides for the Synthesis
of Z- or E-configured Buta-1,3-dien-2-yl
esters
Sachin Bhausaheb Wagh and Rai-Shung Liu*
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 5