Neighboring Carbonyl Group Assisted Oxyacetoxylation of Propargylic Carboxylates with Retention of Chirality under Metal Free Condition

Article abstract of DOI:10.1002/adsc.201900314

A metal-free oxyacetoxylation method of primary, secondary and tertiary propargylic carboxylates with retention of chirality was presented. The reaction proceeds through the intramolecular nucleophilic attack of the neighboring carbonyl group on an alkynyliodonium intermediate. The process is general with broad substrate scope and is amenable for application to a variety of propargyl carboxylates including those obtained from natural products. Insight into the mechanistic pathway by isotopic labelling (using H₂O¹⁸ and D₂O) and controlled experiments confirmed. (Figure presented.).

Full text of DOI:10.1002/adsc.201900314

Title: Neighboring Carbonyl Group Assisted Oxyacetoxylation of
Propargylic Carboxylates with Retention of Chirality under Metal
Free Condition
Authors: Tapas Pradhan and Debendra K. Mohapatra
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201900314
Link to VoR: http://dx.doi.org/10.1002/adsc.201900314

10.1002/adsc.201900314
Advanced Synthesis & Catalysis
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Neighboring Carbonyl Group Assisted Oxyacetoxylation of
Propargylic Carboxylates with Retention of Chirality under
Metal Free Condition
Tapas R. Pradhan,a* Debendra K. Mohapatraa*
aDepartment of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad-
500007, India
*E-mail: tapasranjan3486@gmail.com, mohapatra@iict.res.in
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Many elegant methods are developed using
hypervalent iodine affording oxyacetoxylation
product through C≡C bond activation.[7-10] Some of
the drawbacks of this strategy involves acetic acid at
elevated temperature,[7a-d] and metal catalysts like
Fe[6a] and Ag.[6b] The first report of a metal free
oxidation of alkynes was published by Tamura et
al.[11] utilizing alkynyliodonium intermediate.
Recently, Su and Mo et al.[5] exploited the same
concept for synthesizing α,α׳–diacetoxy ketone via
the assistance of a neighboring hydroxyl group.
However, the later method is limited to tertiary
substrates only, and the process is mitigated by the
Abstract.
A metal-free oxyacetoxylation method of
primary, secondary and tertiary propargylic acetates with
retention of chirality was presented. The reaction proceeds
through the intramolecular nucleophilic attack of the
neighboring carbonyl group on an alkynyliodonium
intermediate. The process is general with broad substrate
scope and is amenable for application to a variety of
propargyl carboxylates including those obtained from
natural products. Insight into the mechanistic pathway by
isotopic labelling (using H2O18 and D2O) and controlled
experiments confirmed.
Keywords: Oxyacetoxylation; Assisted reaction; 5-exo-
dig; Hypervalent iodine; Isotopic labelling
Synthetic strategy for difunctionalization of
unsaturated C-C bonds is a useful strategy for the
modifications of structural motifs of biologically
active compounds.[1-4] Synthetic methods for the
regioselective construction of multiple C-O bonds
from alkenes/alkynes represents an important
transformation. Specifically, the difunctionalization
of propargylic acetates offers a unique opportunity to
access as a three carbon modifiable building block for
the synthesis of intermediates having profound
synthetic or pharmaceutical value.[5] In this regard,
oxyacetoxylation of alkynes[6,7] is considered as one
of the imperative oxidation approach for introducing
C-O bonds, where the distal carbon of alkyne
oxidizes to carbonyl functionality and the terminal
carbon links with a C-OAc bond. Introduction of
α,α׳–dihydroxy ketone[2] or glycerol functionalities[3]
during the synthesis of biologically active
glucocorticoid steroids such as betamethasone,[6]
pirarubicin,[5] fluocinonide,[4] and disaccharides[7] is a
challenging aspect. Some of the methods for the
installation of such include the bromination of ketone
followed by acetolysis and lead tetraacetate oxidation
of an enamide intermediate.[9]
Scheme 1. Neighboring group assisted alkyne function-
alization
the use of 3 to 4 equivalents of BAIB in AcOH at
high temperature making the process unsuitable for a
large scale synthesis as well as functional group
tolerance. The major drawback of this process is the
loss of chirality of the formed oxyacetoxylated
product (Scheme 1A) owing to the carbocation
intermediate in the reaction.
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900314
Advanced Synthesis & Catalysis
To address these issues, we anticipated to employ
neighboring group assisted functionalization[12]
recently developed in our laboratory for the
oxyacetoxylation of alkynes. Indeed, the previous
investigation from us[13a] as well as Sahoo group[13b,c]
showed that by using Au-(I) catalyst and H2O
undergoes oxygen transposition from neighboring
carboxylate functionality to the α-carbon without the
cleavage of C-OCOR bond (Scheme 1B). Taking clue
from this, we envisaged that similar process would be
positioned α- to the acetate bearing carbon provided
the corresponding α,α׳-diacetoxy ketone in very good
yield (86% to 91%). The tertiary carboxylates (1e-1g)
took slightly longer time, whereas the halo and MOM
protecting groups were inert to the reaction
conditions. It is noteworthy to mention that the
presence of olefinic (1h, j, k) or acetylenic
functionalities (1i) which are sensitive to metal
catalysis are intact and furnished the desired products
in good yields. The formation of oxyacetoxylation
product in favor of 2ia with respect to 2ib, could be
due to the presence of neighboring carboxylate group
which facilitates the selective functionalization of the
alkyne[15] via alkynyliodonium intermediate.[7a] Its
noteworthy that propargyl acetate furnished the
product 2l[16] in excellent yields in 1 h, demonstrating
the high efficiency of a less hindered primary acetate
assisted reaction.
feasible
for
an
oxidatively
generated
alkynyliodonium species A and the oxyacetoxylation
via C−O bond cleavage could be ceased and will
stand as a solution for the previous unsolved
problems of racemization[5] (Scheme 1C).
Consequently, synthesis of the high value-added α,α׳–
diacetoxy ketone could be achieved under metal free
conditions using water as the nucleophilic source.
In order to evaluate the viability of the proposed
hypothesis, we initiated the study with the known
secondary carboxylate 1a[14] using an oxidant
(diacetoxyiodo) benzene (BAIB) in the presence or
absence of metal catalysts (Table S1). Careful
standardization revealed that the optimum conditions
(entry 9, Table S1), comprising the use of 1.5 equiv.
of BAIB and 3 equiv. of water in acetonitrile as
solvent at 50 oC gave the product in 92% yield. After
having the optimized conditions, the substrate scope
was examined with various propargylic carboxylates.
As shown in Table 1, variation of electron donating
or withdrawing substitutions in the aromatic ring
Encouraged by the results of the acetate-assisted
oxyacetoxylation, we examined the effect of other
acetates having variable substitutions (Table 2). The
reaction proceeded equally well with propargyl
acetates possessing pivalate, benzoates and trans-
cinamate tether affording the corresponding products
(4a-e) in 78% to 92% yield. Notably, no
isomerization of trans-cinamate group was observed.
The attempt for the double oxyacetoxylation of a
symmetrical dialkynoate bispropargyl succinate 3f
using 3 equiv. of BAIB was not fruitful, however the
mono-oxyacetoxylation product 4f was obtained in
68% yield. The presence of other functional groups
such as enolizable ketoester (3g) furnished the α-
Table 1. Scope of the oxyacetoxylation of various pro-
pargylic carboxylate[a,b]
Table 2. Examination of directing effect of carbonyl
groups other than acetae[a,b]
[a]Unless otherwise noted, reaction was performed with 0.5
mmol of 3 under the standard conditions.
[b]Isolated yields.
[a]Unless otherwise noted, reaction was performed with 0.5
mmol of 1, under optimal conditions.
[c]Performed with 3.0 equiv of BAIB.
[d]Performed at reflux temperature.
[b]Isolated yields.
[e]Reaction was continued to stir for 24 h.
[c]Performed with 1.2 equiv of BAIB.
[d]Performed in one pot starting from propargylic alcohol.
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900314
Advanced Synthesis & Catalysis
acylation product 4g in 48% yield. The presence of
carbonate (3h) furnished products in trace amounts
while the presence of carbamate (3i) gave a complex
mixture of products. The secondary carboxylates such
as pivalate (3k), isovalerate (3l), cinnamate (3m),
benzoate (3n) including heterocycle as well as
bridged carboxylate (3o and 3p) underwent smooth
oxyacetoxylation demonstrating the versatility of the
reaction.
delivered the desired products in excellent yields
without the formation of other diastereomers. It is
noteworthy to mention here that the acid labile
protecting groups such as OTBS, OBn and OPMB
were intact under the optimized conditions (Table
3A). To further explore the synthetic utility,
demonstrated the reaction with propargyl acetates
obtained from complex natural products (Table 3B).
For instance, both the tertiary carboxylates 5f and 5g
derived from ethiosterone and (+)-α-pinene
The support for the mechanistic insights was
validated from the reaction of various chiral
carboxylates (Table 3). At first, the reaction was
demonstrated with a tertiary propargyl carboxylate 5a
in order to rule out the cationic pathway. As expected,
the optimized conditions provided 6a in 92% isolated
underwent
smooth oxyacetoxylation without
effecting the existing functionalities and chirality
(dr> 49:1), thus providing a practical solution which
were otherwise prepared by compromising the
chirality.[5] Similarly, the derivatized tertiary acrylate
of (+)-carvone 5h gave the desired product 6h in 76%
yield without epimerization. Propargyl acetates
obtained from the D-glucose, (+)-α-pinene, natural
amino acid (L-proline) and esterone derived
substrates (5i-l) furnished the corresponding
oxyacetoxy products in good yields. The above
results demonstrated the mildness of the reaction
conditions which are practical to afford
functionalized complex molecules which was not
possible under conditions containing excess amount
of acetic acid.[5,7a-d]
28
yield with an optical rotation value ([α]D −11.3).
This estimation was further substantiated by the
comparison of the diastereomeric ratios of 6b and 6c
with the corresponding carboxylates (benzoate 5b
and acetate 5c). The diastereomeric carboxylates 5d
and 5e with two different assisted groups also
Table 3. Chirality retention and synthetic application of
the oxyacetoxylation[a,b]
Further, deuterium-labelled compound 6l-D was
synthesized in high degree of deuterium
incorporation (cal. 83%). This use of deuterated
alkyne will serve as a useful route for selective
deuteration at the α-position to carbonyl group, which
otherwise cannot be synthesized selectively by any of
the known methods in presence of exchangeable
acidic protons (Table 3C, right).
We explored the scalability and selective
manipulations of the carbonyl functionalities to
intermediates of synthetic value (Scheme 2). Thus in
a gram scale experiment propargylic acetate and
[a]Unless otherwise noted, reaction was performed with 0.5
mmol of 5 under the standard conditions for 6 h.
[b]Isolated yields.
Scheme
2.
Scalability and
diversification of
[c]D2O was used instead of H2O; dr> 49:1 means no
detection of other isomer in NMR.
oxyacetoxylated products (The experimental details of the
above transformations are described in Supporting
Information).
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900314
Advanced Synthesis & Catalysis
benzoate 7a and 7b were successfully transformed to
more than 1.0 g of the corresponding functionalized
products (see SI). With good quantities of products
7a and 7b in hand, we set out to demonstrate
selective functional group manipulations by taking
the advantages of differential reactivity. Reaction of
7a with Lewis acid–catalysis was used to removed
both the primary and tertiary carboxylate groups to
provide α,α׳-dihydroxy ketone 7ai (71% yield) while
the DIBAL-H reaction of 7a furnished the glycerol
derivative 7aii from 7a (Scheme 2). Similarly, the
chemoselective transformations of the product 7b via
(a) reduction of ketone functionality using 1.1 equiv.
of NaBH4 to 7bi, (b) reduction of both primary
carboxylate and ketone carbonyl in presence of 2.2
equiv. of NaBH4 to 7bii, and (c) Sc(OTf)3-catalyzed
deacetylation to α-hydroxy ketone 7biii were
achieved in good yields (Scheme 2). Post
functionalization of 7biii to oxo-α,β-unsaturated ester
7biii′ via an one-pot oxidation Wittig reaction,[17] also
proceeded smoothly. To demonstrate the versatility of
this methodology, DIBAL-H reduction (4 equiv.) of
chiral substrate 6e was performed to furnish triol 6e′
in 81% yield (Scheme 2).
studies were undertaken, where both the isotopic
water (D2O and H2O18) was used. Reaction of 2e
under the optimal conditions[18] in presence of 6 equiv.
of D2O produced 2e-D in >95% deuterium
incorporation (Scheme 3B) indicating that
protonolysis and enol-tautomerization occurred
during this transformation via the formation of
intermediates B-D. The use of 6 equiv. of H2O18
under the standard conditions furnished the labelled
acetate 2a-18O, the formation of which could be
further supported by HRMS of the isotope-labelled
free α,α׳-dihydroxy ketone 2a′′ (see SI); which is
consistent with a scenario where a neighboring
carbonyl group is completely assisting the
oxyacetoxylation of alkyne in presence of water.
After getting the exact information on the source of
carbonyl oxygen, we turned our attention to
investigate the source of terminal acetate
functionality. Thus, the reaction using other
carboxylate source such as propionic acid; the
product 2a was isolated in 66% yield as the only
product (Scheme 3D), clearly indicating that BAIB is
the terminal acetate source. However, the reason is
not clear for the decomposition of 1a in presence of
reactive hypervalent iodine-(III), phenyliodine-bis-
(trifluoroacetate) (Scheme 3E). Similarly, the
propargylic alcohol 1a′ under optimized reaction
conditions proceeded with minimal conversion and
no desired product 2a was observed, thus permeating
the necessity of carboxylate functionality (Scheme
3F).
Given the improved synthetic scope of the
oxyacetoxylation reaction with respect to both achiral
and chiral propargylic carboxylates (with retention of
chirality), we examined the reaction mechanism
(Scheme 3). When propargylic acetate 1a was
subjected to reaction without addition of water, the
desired oxyacetoxylation product 2a was obtained
only in 12% yield even after heating the reaction
mixture for 24 h, revealing the requirement of water
for the oxyacetoxylation (Scheme 3A). Previous
studies on alkyne functionalization supports that
Considering the above results with D2O and labelled
H2O18 (For details, See SI), we herein propose a
plausible mechanistic pathway outlined in Scheme 4.
The initial step involves the formation of
alkynyliodonium salt (A) by the reaction of alkyne
carboxylate 1a with PhI(OAc)2. The oxyacetoxylation
via such intermediate rather than the alternative
Lewis acid-mediated activation of C≡C bond is
validated from the results of the γ-substituted
alkynoate 8 (Scheme 3G). The subsequent 5-exo-dig
BAIB
promotes
alkyne
oxidation
via
alkynyliodonium intermediate A.[5,9b] We sought to
evaluate whether such an intermediate will facilitate
the oxyacetoxylation process through the nucleophilic
attack of the neighboring acetate group. To gain
evidence for the proposed pathway, isotopic labelling
Scheme 4. A plausible mechanism for the assisted oxy-
acetoxylation
Scheme 3. Experimental mechanistic studies
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900314
Advanced Synthesis & Catalysis
attack of the carbonyl oxygen on the β-carbon
generates five-membered electrophilic species B. The
formation of this intermediate can be attributed to the
electron deficient nature of the β-carbon, which
selectively renders such migration by developing a
negative charge on the α-carbon. The nucleophilic
addition of water to B followed by subsequent
protonation of the vinyl carbanion C forms the vinyl
iodonium salt D. This step is affirmed to be reversible
since there is no D-incorporation as would expected
to form the more acidic species AcOD (if 1a is D-1a)
in the first oxidation step (Scheme 3H). The proposed
alternative protonation (from electrophilic H+
generated from C) pathway may be ascribed to the
easier intramolecular delivery of proton in
intermediate C generating D, which rearranges to
enol-iodonium salt E. Product 2a was then produced
through sequential keto/enol tautomerization and
reductive elimination of phenyl iodonium salt E.
Although we cannot definitively rule out the
substitution pathways,[6] we view it as highly unlikely
on the basis of observation from the controlled
experiment with other nucleophilic source.
of the XII Five Year Plan Programme under the title ORIGIN
(CSC-0108);
Manuscript
Communication
Number
IICT/Pubs/2019/164. T.R.P. thanks CSIR, New Delhi, India, for
financial assistance in the form of fellowship.
References
[1] For aerobic difunctionalization of terminal alkynes,
see: a) K. Ji, Y. Zhao, L. Zhang, Angew. Chem., Int.
Ed. 2013, 52, 6508; b) D. C. Mohan, S. N. Rao, S.
Adimurthy, J. Org. Chem. 2013, 78, 1266; c) S. Li, Z.
K. Li, Y. F. Yuan, Y. J. Li, L. S. Zhang, Y. M. Wu,
Chem. Eur. J. 2013, 19, 1496; d) W. Wei, X. Y. Hu,
X. W. Yan, Q. Zhang, M. Cheng, J. X. Ji, Chem.
Commun. 2012, 48, 305; e) A. S. Hashmi, M. C. B.
Jaimes, A. M. Schuster, F. Rominger, J. Org. Chem.
2012, 77, 6394; f) C. Zhang, N. Jiao, J. Am. Chem.
Soc. 2010, 132, 28; g) A.Wang, H. F. Jiang, J. Am.
Chem. Soc. 2008, 130, 5030.
[2] For metal-catalyzed internal alkyne difunctionalization
for heterocycle synthesis, see: a) P. Tian, S. Cai, Q.
Liang, X. Zhou, Y. Xu, T. Loh, Org. Lett. 2015, 17,
1636 and see the references there in; b) F. Zhao, D.
Zhang, Y. Nian, L. Zhang, W. Yang, H. H. Liu, Org.
Lett. 2014, 16, 5124; c) D. Fujino, H. Yorimitsu, A.
Osuka, J. Am. Chem. Soc. 2014, 136, 6255; d) A.
Maji, A. Hazra, D. Maiti, Org. Lett. 2014, 16, 4524;
e) A. J. Walkinshaw, W. Xu, M. G. Suero, M. J.
Gaunt, J. Am. Chem. Soc. 2013, 135, 12532; f) L. Liu,
L. Zhang, Angew. Chem., Int. Ed. 2012, 51, 7301; g)
Y. Wang, K. Ji, S. Lan, L. Zhang, Angew. Chem., Int.
Ed. 2012, 51, 1915; h) E. L. Noey, Y. Luo, L. Zhang,
K. N. Houk, J. Am. Chem. Soc. 2012, 134, 1078; i) L.
W. Ye, L.Cui, G. Z. Zhang, L. M. Zhang, J. Am.
Chem. Soc. 2010, 132, 3258; j) L.Ye, W. He, L.
Zhang, J. Am. Chem. Soc. 2010, 132, 8550; k) H. Cao,
H. Jiang, W. Yao, X. Liu, Org. Lett. 2009, 11, 1931;
l) G. Li, X. Huang, L. Zhang, Angew. Chem., Int. Ed.
2008, 47, 346.
In summary, we have developed a metal free alkyne
oxyacetoxylation method for the direct access of α,α׳-
diacetoxy ketone with retention of configuration. For
such transformation, adopting a condition which uses
water as one of the nucleophilic source offers not
only practical environmental benefits but also lead to
minimize the stoichiometry of BAIB. The chirality
retention at propargylic position, argues for a new
mechanism proceeding via the assistance of a
neighboring acetate, which was further demonstrated
by isotopic labeling and controlled experiments. The
process is general with broad substrate scope and is
amenable for application to a variety of propargyl
carboxylates including those obtained from natural
products. We anticipate that the current concept of
neighboring
group
assisted
metal
free
functionalization chemistry will help to broaden the
other related transformations.
[3] For transition metal catalyzed addition of heteroatoms
to alkynes, see: a) A. Mukherjee, R. B. Dateer,R.;
Chaudhuri,S. Bhunia, S. N. Karad, R. Liu,J. Am.
Chem. Soc. 2011, 133, 15372; b) C.-F. Xu, M. Xu,
Y.-X.Jia, C.-Y. Li, Org. Lett. 2011, 13, 1556 and
references cited therein; c) L. Ye, W. He, L. Zhang,
Angew. Chem., Int. Ed. 2011, 50, 3236; d) D. Vasu,
H.-H. Hung, S. Bhunia, S. A. Gawade, A. Das, R.-S.
Liu, Angew. Chem., Int. Ed. 2011, 50, 6911; e) N.
Taniguchi, Tetrahedron 2009, 65, 2782; f) N.
Taniguchi, Synlett 2008, 6, 849.
Experimental Section
Representative procedure for the BAIB-mediated
oxyacetoxylation: To
a 7 mL screw capped vial
containing propargylic carboxylate 1 (0.5 mmol, 1.0 equiv)
in acetonitrile (1 mL) was added (diacetoxyiodo)benzene
(241 mg, 0.75 mmol, 1.5 equiv.) in one portion followed
by distilled water (27 μL, 1.5 mmol, 3.0 equiv.). The
o
resultant mixture was heated at 50 C for 6 h during which
a white turbid solution was formed. After completion of
the reaction (monitored by TLC), solvent was removed
under reduced pressure and the crude residue was adsorbed
with silica gel for chromatographic purification using ethyl
acetate and hexane (≈1:4) to afford the desired
oxyacetoxylated products up to 94% yield.
[4] For synthesis of some valuable intermediates by
alkyne oxidation, see: a) M. Zhou, M. Chen, Y. Yao
Zhou, K. Yang, J. Su, J. J. Du, Q. Song, Org.
Lett. 2015, 17, 1786; b) Y.–T. He, Q. Wang, L.–H. Li,
X.–Y. Liu, P.–F. Xu, Y.–M. Liang, Org. Lett.
2015, 17, 518; c) Q. Lu, J. Zhang, G. Zhao, Y. Qi, H.
Wang, A. Lei, J. Am. Chem. Soc. 2013, 135, 11481;
d) T. Sawangphon, P. Katrun, K. Chaisiwamongkhol,
M. Pohmakotr, V. Reutrakul, T. Jaipetch, D.
Soorukram, C. Kuhakarn, Synth. Commun. 2013, 43,
1692; e) X. Q. Li, X. S. Xu, X. H. Shi, Tetrahedron
Acknowledgements
The authors thank the Council of Scientific and Industrial
Research (CSIR), New Delhi, India, for financial support as part
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900314
Advanced Synthesis & Catalysis
Lett. 2013, 54, 3071; f) P. Katrun, S.
Dominguez, I. Moreno, R. SanMartin, Org. Lett.
2005, 7, 3073; g) J. M. Chen, X. Huang, Synthesis
2004, 15, 2459.
Chiampanichayakul, K. Korworapan, M. Pohmakotr,
V. Reutrakul, T. Jaipetch, C. Kuhakarn, Eur. J. Org.
Chem. 2010, 5633; f) V. Nair, A. Augustine, T. D.
Suja, Synthesis, 2002, 2259.
[11] Y. Tamura, T. Yakura, J. Haruta, Y. Kita,
Tetrahedron Lett. 1985, 26, 3837.
[5] Q.-R. Liu, C.-X. Pan, X.-P. Ma, D.-L. Mo, G.-F. Su,
J. Org. Chem. 2015, 80, 6496 and the references cited
therein.
[12] a) For a recent review, see; S. Wang, Tetrahedron
Lett. 2018, 59, 1317; For some selected
transformations involving 1,2-acyloxy migration, see:
b) E. Jimenez-Nuꢁez, A. M. Echavarren, Chem.
Commun. 2007, 333; c) J. Barluenga, L. Riesgo, R.
Vicente, L. Lopez, M. Tomas, J. Am. Chem. Soc.
2007, 129, 7772; d) A. S. K. Hashmi, G. J. Hutchings,
Angew. Chem., Int. Ed. 2006, 45, 7896; e) S. Wang, L.
Zhang, J. Am. Chem. Soc. 2006, 128, 14274; f) L.
Zhang, S. Wang, J. Am. Chem. Soc. 2006, 128, 1442;
g) D. J. Gorin, P. Dube, F. D. Toste, J. Am. Chem.
Soc. 2006, 128, 14480; h) M. J. Johansson, D. J.
Gorin, S. T. Staben, F. D. Toste, J. Am. Chem. Soc.
2005, 127, 18002.
[6] For metal-catalyzed alkyne oxyacetoxylation, see: a)
B. T. V. Srinivas, V. S. Rawat, B. Sreedhara, Adv.
Synth. Catal. 2015, 357, 3587; b) G. Deng, J. Luo,
Tetrahedron 2013, 69, 5937; c) C. Wu, Z. Liang, D.
Yan, W. He, J. Xiang, Synthesis 2013, 45, 2605; d)
T.-K. Zhang, D.-L. Mo, L.-X. Dai, X.-L. Hou, Org.
Lett. 2008, 10, 3689; e) P. J. Stang, A. M. Arif, C. M.
Crittell, Angew. Chem., Int. Ed. 1990, 29, 287; f) T.
Kitamura, M. Kotani, Y. Fujiwara, Synthesis 1998,
1416; g) K. L. Reed, J. T. Gupton, K. L. McFarlane,
Synth. Commun. 1989, 19, 2595.
[7] For metal-free alkyne oxyacetoxylation, see: a) ref 6;
b) D.-L. Mo, L.-X. Dai, X.-L. Hou, Tetrahedron Lett.
2009, 50, 5578; c) M. S. Yusubov, G. A. Zholobova,
I. L. Filimonova, K.-W. Chi, Russ. Chem. Bull. Int.
Ed. 2004, 53, 1735; d) M. S.Yusubov, G. A.
Zholobova, Russ. J. Org. Chem. 2001, 37, 1179; e) M.
Ochiai, Kunishima, M.; Fuji, K.; Nagao, Y. J. Org.
Chem. 1989, 54, 4038.
[13] For selected examples of alkyne monofunctionali-
zation assisted by neighboring carbonyl group, see: a)
T. R. Pradhan, K. L. Mendhekar, D. K. Mohapatra, J.
Org. Chem. 2015, 80, 5517; b) N. Ghosh, S. Nayak,
B. Prabagar, A. K. Sahoo, J. Org. Chem. 2014, 79,
2453; c) N. Ghosh, S. Nayak, A. K. Sahoo, J. Org.
Chem. 2011, 76, 500.
[14] R. J. Detz, M. M. E. Delville, H. Hiemstra, J. H. van
[8] For some reviews of hypervalent iodine reagents, see
a) T. Dohi, Y. Kita, Chem. Commun. 2009, 2073; b)
V. V. Zhdankin, P. J. Stang, Chem. Rev. 2008, 108,
5299; c) T. Wirth, Angew. Chem., Int. Ed. 2005, 44,
3656; d) V. V. Zhdankin, P. J. Stang, Chem. Rev.
2002, 102, 2523.
Maarseveen, Angew. Chem. Int. Ed. 2008, 47, 3777.
[15] The assisted oxyacetoxylation product 2ia could not
be isolated from the undesired product 2ib and the
ratio of them was determined as2:1 from the 1H NMR
spectrum (See SI).
[16] As the propargylic acetate 1l is volatile in nature, we
attempted the oxyacetoxylation of propargylic
alcohol in one pot but stepwise manner; the
acetylation of propargylic alcohol was carried out
with acetic anhydride in presence of catalytic amount
of DMAP and the subsequent oxyacetoxylation was
performed under the optimized conditions (entry 9,
Table S1).
[9] For some examples of hypervalent iodine reagents in
organic synthesis, see a) J. Y. Sun, D. Zhang-
Negrerie, Y. F. Du, K. Zhao, J. Org. Chem. 2015, 80,
1200 and the references cited therein; b) C.-Y. Zhao,
L.-G. Li, Q.-R. Liu, C.-X. Pan, G.-F. Su, D.-L. Mo,
Org. Biomol. Chem. 2016, 14, 6795; c) C.-Y. Zhao, K.
Li, Y. Pang, J.-Q. Li, C. Liang, G.-F. Su, D.-L. Mo,
Adv. Synth. Catal. 2018, 360, 1919.
[17] X. Wei, R. J. K. Taylor. Tetrahedron Lett. 1998, 39,
[10] For some examples related to alkyne activation by
PhI(OAc)2, see: a) Q. Jiang, A. Zhao, C. Guo, J. Org.
Chem. 2014, 79, 2709; b) J. A. Souto, P. Becker, ꢀ.
Lglesias, K. Muniz, J. Am. Chem. Soc. 2012, 134,
15505; c) D. L. Mo, C. H. Ding, L. X. Dai, X. L. Hou,
Chem. Asian J. 2011, 6, 3200; d) A. Saito, A.
Matsumoto,Y. J. Hanzawa, Tetrahedron Lett. 2010,
51, 2247; e) I. Tellitu, S. Serna, M. T. Herrero, I.
Moreno, E. Dominguez, R. J. SanMartin, J. Org.
Chem. 2007, 72, 1526; f) S. Serna, I. Tellitu, E.
3815.
[18] We preferred the tertiary caboxylate 2e so as to verify
that even for a tertiary carboxylate, the nucleophilic
attack of water to the electrophilic intermediate B
generated via nucleophilic attack of acetoxy group is
facile.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900314
Advanced Synthesis & Catalysis
UPDATE
Neighboring Carbonyl Group Enabled Oxyacetoxy-
lation with Retention of Chirality under Metal Free
Conditions
Adv. Synth. Catal. Year, Volume, Page – Page
Tapas R. Pradhan,* Debendra K. Mohapatra*
7
This article is protected by copyright. All rights reserved.