A Phosphonium Ylide as an Ionic Nucleophilic Catalyst for Primary Hydroxyl Group Selective Acylation of Diols

Article abstract of DOI:10.1021/acscatal.7b02281

Carbonyl-stabilized phosphonium ylides exhibit great utility in modern organic synthesis, and they are known as an ambident nucleophile at the carbonyl oxygen atom and at the α-carbon atom. However, they have found limited use as catalysts. We focused on the inherent nucleophilicity of the oxygen atom to develop an ionic nucleophilic catalysis, and the phosphonium ylide-catalyzed primary alcohol selective acylation of mixed diols with acid anhydrides has been demonstrated. Mechanistic studies revealed the behavior of a catalyst, which would contribute to the field of ylide chemistry.

Full text of DOI:10.1021/acscatal.7b02281

Subscriber access provided by UNIVERSITY OF ADELAIDE LIBRARIES
Letter
A Phosphonium Ylide as an Ionic Nucleophilic Catalyst
for Primary Hydroxyl Group Selective Acylation of Diols
Yasunori Toda, Tomoyuki Sakamoto, Yutaka Komiyama, Ayaka Kikuchi, and Hiroyuki Suga
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.7b02281 • Publication Date (Web): 10 Aug 2017
Downloaded from http://pubs.acs.org on August 11, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
ACS Catalysis is published by the American Chemical Society. 1155 Sixteenth Street
N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 6
ACS Catalysis
1
2
3
4
5
6
7
8
9
A Phosphonium Ylide as an Ionic Nucleophilic Catalyst for
Primary Hydroxyl Group Selective Acylation of Diols
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Yasunori Toda,* Tomoyuki Sakamoto, Yutaka Komiyama, Ayaka Kikuchi, and Hiroyuki Suga*
Department of Materials Chemistry, Faculty of Engineering, Shinshu University, 4ꢀ17ꢀ1 Wakasato, Nagano 380ꢀ8553, Japan
ABSTRACT: Carbonylꢀstabilized phosphonium ylides exhibit great utility in modern organic synthesis, and are known as an amꢀ
bident nucleophile at the carbonyl oxygen atom and at the αꢀcarbon atom. However, they have found limited use as catalysts. We
focused on the inherent nucleophilicity of the oxygen atom to develop an ionic nucleophilic catalysis, and the phosphonium ylideꢀ
catalyzed primary alcohol selective acylation of mixed diols with acid anhydrides has been demonstrated. Mechanistic studies reꢀ
vealed the behavior of a catalyst, which would contribute to the field of ylide chemistry.
KEYWORDS: phosphonium ylides, nucleophilic catalysts, organocatalysis, acylation, diols
Phosphonium (Pꢀ) ylides – the cationic site is composed of a
phosphonium ion and the negatively charged atom directly
attached to the phosphorus center – are a specific type of zwitꢀ
terion, and are commonly used or invoked as a key intermediꢀ
ate in the Wittig reaction.1 Taking account of the nucleophilicꢀ
ity of the anionic carbon, versatile transformations have been
accomplished.2ꢀ4 Despite being attractive chemical species,
however, their catalytic ability has remained elusive until toꢀ
day presumably due to difficulty in regeneration of the Pꢀ
ylide.4,5 Hence the development of Pꢀylide catalysis is of forꢀ
midable challenge and can open a new frontier for the field of
ylide chemistry.
Carbonylꢀstabilized Pꢀylides, playing an important role in
modern organic synthesis,2dꢀe,3aꢀe,4dꢀf are known as ambident
nucleophiles.6 Recently, Byrne and Mayr et al. reported on the
mechanism of the reaction of formylꢀ and acetylꢀstabilized Pꢀ
ylides.7 On the basis of their study, Oꢀattack by the ylides toꢀ
ward carbon electrophiles, e.g. benzhydrylium ions, alkyl halꢀ
ides, acyl chlorides, is intrinsically and kinetically favored. It
has also been shown that the Cꢀacetylated, thermodynamicalꢀ
lyꢀfavored, product was obtained exclusively in the reaction
with acetic anhydride. Therefore, it could be feasible to estabꢀ
lish nucleophilic catalysis by the stabilized ylide if Oꢀacylated
intermediate is allowed to undergo acylꢀtransfer to external
nucleophiles. For this inquiry, we have designed an ionic orꢀ
ganocatalyst 1 having a novel structural motif (Figure 1). The
Figure 1. Working hypothesis: The design and synthesis of a
phosphonium ylide as an ionic nucleophilic catalyst for acyl
transfer reactions.
aryl group introduced into the ylide carbon moiety is expected
to prevent undesired Cꢀacylation, because Oꢀacylation proꢀ
vides not only a kinetically stable product but also a thermoꢀ
dynamically stable product owing to the aromatic stabilizaꢀ
tion.8 The carboxylate ion derived from acid anhydride, in
turn, could be positioned proximal to the phosphonium ion,
control methods, especially by Lewis acidic metals, have been
developed to date.12 By contrast, few organic small molecules
which would guide the nucleophile towards the carbonyl
group of Oꢀacylated intermediate.9 Thus, we reasoned that
acylation of alcohols might be a suitable transformation for
identifying a behavior of 1 as an ionic nucleophilic catalyst.10
have
used
for
this
purpose,13
although
4ꢀ
dimethylaminopyridine (DMAP) is a very effective catalyst
for alcohol acylation with acid anhydrides.9a,14 This communiꢀ
cation describes the exploration of a phosphonium ylide cataꢀ
lyst that can achieve the primary alcohol selective acylation of
primaryꢀsecondary diols with high conversion using commerꢀ
cially available acid anhydrides.
As often encountered in organic synthesis, selective acyl
protection of a primary hydroxyl group in the presence of secꢀ
ondary hydroxyl group(s) exhibits great utility. In addition to
conventional reagentꢀcontrol methods,11 a number of catalystꢀ
ACS Paragon Plus Environment

ACS Catalysis
First, we synthesized Pꢀylide 1a (Figure 1, G1 = H, G2 =
Page 2 of 6
Me) from its hydrobromic acid salt 1a·HBr.15 It can be
assumed that dehydrohalogenation of phosphonium salts
would provide the corresponding ylides, and treatment of
1a·HBr with sodium hydroxide in methanol and trituration
with dichloromethane/hexane afforded 1a as a stable solid.
The 3Dꢀstructure of 1a was confirmed by Xꢀray
crystallographic analysis (Figure 2a). The observed PꢀC1 bond
length [1.764(1) Å] is slightly longer than that of typical
unstabilized phosphonium ylides,16a and the observed OꢀC2
bond length [1.284(2) Å] is similar to that of carbonylꢀ
stabilized yildes.16b In addition, the length of C1ꢀC2 bond
[1.431(2) Å] is between a phenyl ring (1.40 Å) and a normal
Csp2ꢀCsp2 single bond (1.46 Å).16c These bond lengths and the
torsion angle of PꢀC1ꢀC2ꢀO [0.2(2)°] suggested electron
delocalization within the ylide system. Next, DFT calculations
were performed at the B3LYP/6ꢀ311++G** level of theory.
The optimized structure of 1a obtained is well reflected in the
crystalline state, and thus the molecular electrostatic potential
was also calculated as a simple indicator of the nucleophilic
site of the molecule. As shown in Figure 2b, the negative
potential is concentrated at the oxygen atom, implying that Oꢀ
attack of 1 might predominate. The crystallographic and
theoretical analyses gave impetus to the investigation of the
ylide nucleophilic catalysis further.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
Figure 3. Changes in the H NMR spectrum (300 MHz, CDCl3)
of ylide 1a upon addition of isobutyric anhydride in the range of
6.2ꢀ8.4 ppm. From bottom to top, the spectra of 1a in the presence
of 0.0 equiv (green), 2.5 equiv (blue), 5.0 equiv (purple), 10 equiv
(pink), and 15 equiv (red) of acid anhydride are depicted. The
signals shown by the orange arrows correspond to the aromatic
protons of A.
1
At the outset of our studies, we conducted H NMR experiꢀ
ments to ascertain whether the nucleophilic activation of acid
anhydride by Pꢀylide 1a was possible and also whether the
acylated alcohol could be obtained. The experiments were
performed using a solution of 1a in CDCl3 at room temperaꢀ
ture by adding 2.5ꢀ15 equivalents of isobutyric anhydride
(Figure 3). When ylide 1a was mixed with 2.5 equivalents of
acid anhydride, new signals (shown by arrows) appeared and a
signal of 1a significantly shifted downfield, indicating generaꢀ
tion of Oꢀacylated intermediate A in equilibrium (ca. 30%
conversion based on the integration of 1a).17 After the addition
of excess amount of the anhydride (15 equiv), the bright yelꢀ
low solution turned pale yellow and more than 90% of 1a was
converted to the newly observed species. Thus we attempted
highꢀresolution mass analysis from the NMR sample solution,
and the ESI positive measurement produced a peak at m/z =
439.1832, which corresponds to a phosphonium cation of A.
To our delight, treatment of this solution of A with one
equivalent of 1ꢀheptanol and triethylamine yielded isobutyrate
2 in 98% after 24 hours, whereas only half of the alcohol was
acylated in the absence of 1a (Scheme 1a). It should be noted
Scheme 1. 1H NMR experiments for the development of
phosphonium ylide catalysis
that the ylide regeneration could not be observed during the
course of the reaction probably owing to the rapid formation
of A. This was supported by the competitive reaction between
ylide 1a and 1ꢀheptanol with isobutyric anhydride shown in
Scheme 1b, where acylation of 1a proceeds to generate A
much faster than esterification to 2 (Scheme 1b).
Following results of the feasibility study, we investigated
the selectivity in the acylation of a 1:1 mixture of primary and
secondary alcohols with isobutyric anhydride (Table 1). Conꢀ
trol experiments revealed that the combined use of 1a and an
auxiliary base was important to achieve better conversion with
higher selectivity (Table 1, Entries 1ꢀ4). DMAP afforded a
considerable amount of secondary alcoholꢀacylated product,
while the reactivity was satisfactory (Table 1, Entries 5 and 6).
Similar tendency was also observed in less polar solvents,
such as hexane and toluene (Table 1, Entries 7ꢀ12). Lastly, the
use of 1.5 equivalents of acid anhydride slightly improved
both the yield and selectivity (Table 1, Entry 13). Moreover, in
situ generated ylide can be applicable to this system, leading
to a similar result when 1a·HBr was employed as a precursor
of ylide 1a (Table 1, Entry 14).18
Figure 2. (a) Xꢀray crystal structure of 1a (hydrogen atoms omitꢀ
ted for clarity). Selected bond lengths (Å) and torsion angles (°):
P–C1 1.764(1), OꢀC2 1.284(2); C1ꢀC2 1.431(2); PꢀC1ꢀC2ꢀO
0.2(2). (b) Electrostatic potential map (charge) of 1a on the 0.002
au isodensity surface. The potential is calculated at the B3LYP/6ꢀ
311++G** level of theory and shown with identical chromatic
scales (red is more negative; blue is more positive).
The initial scope of diols 4 is summarized in Table 2. To
minimize an acyl group migration between primary and secꢀ
ondary hydroxyl groups, two reactions were run sideꢀbyꢀside
under the same conditions, one of which was used for moniꢀ
1
toring a reaction progress by H NMR (see Supporting Inforꢀ
ACS Paragon Plus Environment

Page 3 of 6
ACS Catalysis
Table 1. Optimization of phosphonium ylide-catalyzed se-
lective acylation of 1-heptanola
(a)
1a
(10 mol %)
1
2
3
4
HO
HO
(iPrCO)2O (1.5 equiv)
OH
OC(O)iPr
6a
7a
+
+
Ph
Ph
w/o Et3N
4a
5a 81%
:
toluene (0.8 M), rt, 24 h
5a 6a 7a
95% conv.
:
:
= 85:11:4
5
6
7
8
(b)
1a
(10 mol %)
HO
AcO
AcO
Ac2O (1.5 equiv)
OAc
OH
OAc
4a
+
+
Ph
Ph
Ph
w/o Et3N
2
3
selectivity
8a
: 83%
9
10
toluene (0.8 M), rt, 24 h
entry
catalyst
Et3N
solvent
(%)b (%)b
(2:3)b
9
8 9 10
98% conv. : : = 86:5:9
8 9 10
(cf. w/ Et3N; >99% conv. : : = 46:9:45)
1
2
1a
yes
no
CDCl3
CDCl3
79
45
39
32
89
74
79
46
71
82
38
72
90
90
4
5
95:5
90:10
89:11
82:18
77:23
79:21
94:6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1a
(c)
OH OH
OH OAc
3
-
-
yes
no
CDCl3
5
1a
(10 mol %)
Ac2O (1.5 equiv)
BnO
BnO
BnO
BnO
4
CDCl3
7
O
O
5
6c
DMAP
DMAP
1a
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
CDCl3
25
20
5
toluene (0.8 M)
rt, 24 h
4h
8b 93%
:
CDCl3
OMe
OMe
7
hexane
hexane
hexane
toluene
toluene
toluene
toluene
toluene
Scheme 2. Phosphonium ylide-catalyzed acylation with acid
anhydrides under base-free conditions
8
-
10
24
3
82:18
75:25
96:4
9c
10
11
12c
13d
14d
DMAP
1a
the selectivity of acylation and worked up the other reaction
for the best period of isolation. The ratio of 5 and 6 at the peꢀ
riod of quenching those reactions can be estimated from the
NMR tracking (Table 2, shown in parentheses), and primary
monoesters 5aꢀh were isolated as sole products except for the
case of 5i. 1,2ꢀ and 1,3ꢀDiols 4aꢀd afforded the corresponding
products with high selectivity (>95:5) under either condition A
or B. It should be emphasized that 1,2ꢀdiols 4a and 4b underꢀ
went highly selective acylation (e.g. 97:3 for 5a),19 since modꢀ
erate selectivity (e.g. 74:26 for 5a) was observed in the reportꢀ
ed organocatalytic system using imidazobenzothiazoles.13c
Although 1,4ꢀ and 1,5ꢀdiols 4eꢀg were challenging, the use of
catalyst 1b (Figure 1, G1 = G2 = Me) elegantly enhanced the
selectivity. Carbohydrates are also a tempting target, and gluꢀ
cose and xylose derivatives 4h and 4i were tolerated to furnish
5h and 5i in a highly selective fashion, respectively.
-
3
93:7
DMAP
1a
22
4
77:23
96:4
1a·HBr
5
95:5
aUnless otherwise noted, all reactions were carried out using 0.20 mmol
of 1ꢀheptanol, 0.20 mmol of 1ꢀmethylheptanol, and 0.24 mmol of isobuꢀ
tyric anhydride. Determined by H NMR analysis. Reaction time for
15 min. d1.5 equivalents of acid anhydride were used.
b
1
c
Table 2. Scope of diolsa
Furthermore, baseꢀfree conditions were examined since
DMAP has been found to promote acylation of alcohols with
acid anhydrides even in the absence of an auxiliary base.13f As
shown in Scheme 2a, baseꢀfree acylation has been realized
while the selectivity marginally dropped. Notably, primary
alcohol acetylation of 1,2ꢀdiol 4a by Pꢀylide catalysis also
proved successful, affording 8a in 83% isolated yield (Scheme
2b). In contrast, a considerable amount of 1,2ꢀbisꢀacetate 10
was formed with employment of triethylamine, which presents
the advantage of the reactions without bases. Conversion of 4h
to monoꢀacetate 8b was accomplished over 90% isolated yield
(Scheme 2c).
In summary, we have demonstrated phosphonium ylideꢀ
catalyzed primary hydroxyl group selective acylation of diols.
This methodology is applicable to mixed 1,nꢀdiols, affording
monoꢀacylated product in good to high yields. A novel design
of carbonylꢀstabilized ylide 1, tethering the ylide carbon and
carbonyl αꢀcarbon with aromatic system, prefers Oꢀacylation
owing to kinetic and thermodynamic controls. In addition, the
unique behavior of 1 has been identified by mechanistic
studies. Efforts are currently underway to extend phosphonium
ylide catalysis.
aUnless otherwise noted, all reactions were carried out on a 0.40 mmol
scale using 4, 10 mol % of catalyst (1a, 1a·HBr, or 1c), 1.5 equiv of
isobutyric anhydride, and 2.0 equiv of triethylamine in toluene (0.5 mL)
at room temperature. On the basis of the reaction monitoring experiment
by 1H NMR, the selectivity (5:6) was shown in parentheses. bA trace
ASSOCIATED CONTENT
Supporting Information
amount of 6 was contaminating. cNMR yield of 5. Combined yield of 5
d
and 6 (95:5 mixture).
mation for details). On the basis of the results, we determined
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 6
(g) Schirmer, M.ꢀL.; Adomeit, S.; Werner, T. Org. Lett. 2015, 17,
3078–3081. (h) Yan, Y.ꢀM.; Rao, Y.; Ding, M.ꢀW. J. Org. Chem.
2016, 81, 1263–1268.
(5) (a) Kobayashi, M.; Sanda, F.; Endo, T. Macromolecules 1999, 32,
4751–4756. (b) Kobayashi, M.; Sanda, F.; Endo, T. Macromolecules
2000, 33, 5384–5387. (c) Zhou, H.; Wang, G.ꢀX.; Zhang, W.ꢀZ.; Lu,
X.ꢀB. ACS Catal. 2015, 5, 6773–6779.
(6) Johnson, A. W. Ylides and Imines of Phosphorus; Wiley: New
York, 1993, and references therein.
Experimental procedures (PDF), spectroscopic data for all new
compounds (PDF), and crystallographic data for 1a (CIF). This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
2
3
4
5
6
7
8
AUTHOR INFORMATION
Corresponding Authors
*Eꢀmail: ytoda@shinshuꢀu.ac.jp (Y.T.)
*Eꢀmail: sugahio@shinshuꢀu.ac.jp (H.S.)
(7) Byrne, P. A.; Karaghiosoff, K.; Mayr, H. J. Am. Chem. Soc. 2016,
138, 11272–11281.
9
(8) The Cꢀacylated product of 1 is less stable (+38.1 kacl/mol) than
the Oꢀacylated product of 1 on the basis of DFT calculations at the
B3LYP/6ꢀ31+G* level in toluene. See Supporting Information for
details.
(9) (a) Sakakura, A.; Kawajiri, K.; Ohkubo, T.; Kosugi, Y.; Ishihara,
K. J. Am. Chem. Soc. 2007, 129, 14775–14779. (b) Nishino, R.; Fuꢀ
ruta, T.; Kan, K.; Sato, M.; Yamanaka, M.; Sasamori, T.; Tokitoh, N.;
Kawabata, T. Angew. Chem., Int. Ed. 2013, 52, 6445–6449.
Notes
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was partially supported by the Japan Society for the
Promotion of Science (JSPS) through a GrantꢀinꢀAid for Research
Activity Startꢀup (Grant No. JP15H06242). We gratefully
acknowledge Dr. Kenji Yoza (Bruker AXS) for Xꢀray analysis.
We also thank Nippon Shokubai Award in Synthetic Organic
Chemistry, Japan (Y.T.).
(10) Ammonium betaines: (a) Uraguchi, D.; Koshimoto, K.; Miyake,
S.; Ooi, T. Angew. Chem., Int. Ed. 2010, 49, 5567–5569. (b) Uraguchi,
D.; Koshimoto, K.; Ooi, T. J. Am. Chem. Soc. 2012, 134, 6972–6975.
(c) Tsutsumi, Y.; Yamakawa, K.; Yoshida, M.; Ema, T.; Sakai, T.
Org. Lett. 2010, 12, 5728–5731. Pyridine Nꢀoxides: (d) Shiina, I.;
Ushiyama, H.; Yamada, Y.; Kawakita, Y.; Nakata, K. Chem. Asian J.
2008, 3, 454–461. (e) Shiina, I.; Sasaki, A.; Kikuchi, T.; Fukui, H.
Chem. Asian J. 2008, 3, 462–472. (f) Nakajima, M.; Saito, M.; Shiro,
M.; Hashimoto, S. J. Am. Chem. Soc. 1998, 120, 6419–6420. (g)
Klauber, E. G.; Mittal, N.; Shah, T. K.; Seidel, D. Org. Lett. 2011, 13,
2464–2467. (h) Yoshida, K.; Takao, K. Tetrahedron Lett. 2014, 55,
6861–6863. (i) Yoshida, K.; Fujino, Y.; Itatsu, Y.; Inoue, H.; Kanoko,
Y.; Takao, K. Tetrahedron Lett. 2016, 57, 627–631. (j) Murray, J. I.;
Woscholski, R.; Spivey, A. C. Chem. Commun. 2014, 50, 13608–
13611. (k) Murray, J. I.; Woscholski, R.; Spivey, A. C. Synlett 2015,
985–990. (l) Murray, J. I.; Spivey, A. C. Adv. Synth. Catal. 2015, 357,
3825–3830. (m) Ishihara, K.; Lu, Y. Chem. Sci. 2016, 7, 1276–1280.
(11) (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organ-
ic Synthesis, 4th ed.; John Wiley & Sons: New York, 2007. (b)
Wakita, N.; Hara, S. Tetrahedron 2010, 66, 7939–7945. (c) Yamada,
S. J. Org. Chem. 1992, 57, 1591–1592. (d) Yamada, S.; Sugaki, T.;
Matsuzaki, K. J. Org. Chem. 1996, 61, 5932–5938. (e) Ishihara, K.;
Kurihara, H.; Yamamoto, H. J. Org. Chem. 1993, 58, 3791–3793.
(12) Selected examples: (a) Breton, G. W. J. Org. Chem. 1997, 62,
8952–8954. (b) Bianco, A.; Brufani, M.; Melchioni, C.; Romagnoli, P.
Tetrahedron Lett. 1997, 38, 651–652. (c) Procopiou, P. A.; Baugh, S.
P. D.; Flack, S. S.; Inglis, G. G. A. J. Org. Chem. 1998, 63, 2342–
2347. (d) Orita, A.; Mitsutome, A.; Otera, J. J. Org. Chem. 1998, 63,
2420–2421. (e) Lin, M.ꢀH.; RajanBabu, T. V. Org. Lett. 2000, 2, 997–
1000. (f) Ranu, B. C.; Dutta, P.; Sarkar, A. J. Chem. Soc., Parkin
Trans. I 2000, 2223–2225. (g) Clarke, P. A.; Holton, R. A.; Kayaleh,
N. E. Tetrahedron Lett. 2000, 41, 2687–2690. (h) Yadav, V. K.; Babu,
K. G.; Mittal, M. Tetrahedron 2001, 57, 7047–7051. (i) Clarke, P. A.
Tetrahedron Lett. 2002, 43, 4761–4763.
(13) Enzyme catalysis: (a) Ramaswamy, S.; Morgan, B.;
Oehlschlager, A. C. Tetrahedron Lett. 1990, 31, 3405–3048. Iminoꢀ
phosphoranes: (b) Ilankumaran, P.; Verkade, J. G. J. Org. Chem.
1999, 64, 9063–9066. Imidazole and benzothiazole derivatives: (c)
Ibe, K.; Hasegawa, Y.; Shibuno, M.; Shishido, T.; Sakai, Y.; Kosaki,
Y.; Susa, K.; Okamoto, S. Tetrahedron Lett. 2014, 55, 7039–7042.
See also, transesterification/acylation reactions by Nꢀheterocyclic
carbene catalysts: (d) Grasa, G. A.; Güveli, T.; Singh, R.; Nolan, S. P.
J. Org. Chem. 2003, 68, 2812–2819.
(14) (a) Höfle, G.; Steglich, W.; Vorbrüggen, H. Angew. Chem., Int.
Ed. 1978, 17, 569–583. (b) Scriven, E. F. V. Chem. Soc. Rev. 1983,
12, 129–161. (c) Ragnarsson, U.; Grehn, L. Acc. Chem. Res. 1998, 31,
494–501. (d) Grondal, C. Synlett 2003, 1568–1569. (e) Spivey, A. C.;
Arseniyadis, S. Angew. Chem., Int. Ed. 2004, 43, 5436–5441. Tribuꢀ
tylphosphine is also known as a nucleophilic catalyst for acylation. (g)
Vedejs, E.; Diver, S. T. J. Am. Chem. Soc. 1993, 115, 3358–3359. (h)
Vedejs, E.; Bennett, N. S.; Conn, L. M.; Diver, S. T.; Gingras, M.;
REFERENCES
(1) (a) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863–927.
(b) Byrne, P. A.; Gilheany, D. G. Chem. Soc. Rev. 2013, 42, 6670–
6696. (c) Gosney, I.; Rowley, A. G. In Organophosphorus Reagents
in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic Press: London,
1979; p 17. (d) Vedejs, E.; Peterson, M. J. In Topics in Stereochemis-
try; Eliel, E. L., Wilen, S. H., Eds.; Wiley: New York, 1994; Vol. 21,
p 1. (e) Vedejs, E.; Peterson, M. J. In Advances in Carbanion Chemis-
try; Snieckus, V., Ed.; JAI Press: Greenwich, CT, 1996; Vol. 2, p 1.
(f) Schobert, R. In Organophosphorus Reagents; Murphy, P. J., Ed.;
Oxford University Press: Oxford, UK, 2004; p 12. (g) Abell, A. D.;
Edmonds, M. K. In Organophosphorus Reagents; Murphy, P. J., Ed.;
Oxford University Press: Oxford, UK, 2004; p 9. (h) Edmonds, M.;
Abell, A. In Modern Carbonyl Olefination; Takeda, T., Ed.; Wileyꢀ
VCH: Weinheim, Germany, 2004; p 1. (i) Schlosser, M. In Topics in
Stereochemistry; Eliel, E. L., Allinger, N. L., Eds.; Wiley: New York,
1970; Vol. 5, p 1.
(2) (a) Dong, D.ꢀJ.; Li, H.ꢀH.; Tian, S.ꢀK. J. Am. Chem. Soc. 2010,
132, 5018–5020. (b) Dong, D.ꢀJ.; Li, Y.; Wang, J.ꢀQ.; Tian, S.ꢀK.
Chem. Commun. 2011, 47, 2158–2160. (c) Fang, F.; Li, Y.; Tian, S.ꢀ
K. Eur. J. Org. Chem. 2011, 1084–1091. (d) Shanahan, C. S.; Truong,
P.; Mason, S. M.; Leszczynski, J. S.; Doyle, M. P. Org. Lett. 2013, 15,
3642–3645. (e) Cachatra, V.; Almeida, A.; Sardinha, J.; Lucas, S. D.;
Gomes, A.; Vaz, P. D.; Florêncio, M. H.; Nunes, R.; VilaꢀViçosa, D.;
Calhorda, M. J.; Rauter, A. P. Org. Lett. 2015, 17, 5622–5625. (f)
Myśliwiec, D.; Lis, T.; Gregoliński, J.; Stępień, M. J. Org. Chem.
2015, 80, 6300–6312. (g) Spallarossa, M.; Wang, Q.; Riva, R.; Zhu, J.
Org. Lett. 2016, 18, 1622–1625.
(3) Wittig type reactions by transition metal catalysis: (a) Li, C.ꢀY.;
Wang, X.ꢀB.; Sun, X.ꢀL.; Tang, Y.; Zheng, J.ꢀC.; Xu, Z.ꢀH.; Zhou,
Y.ꢀG.; Dai, L.ꢀX. J. Am. Chem. Soc. 2007, 129, 1494–1495. (b) Cao,
P.; Sun, X.ꢀL.; Zhu, B.ꢀH.; Shen, Q.; Xie, Z.; Tang, Y. Org. Lett.
2009, 11, 3048–3051. (c) Chinnusamy, T.; Rodionov, V.; Kühn, F. E.;
Reiser, O. Adv. Synth. Catal. 2012, 354, 1827–1831. (d) Wang, P.;
Liao, S.; Wang, S. R.; Gao, R.ꢀD.; Tang, Y. Chem. Commun. 2013, 49,
7436–7438. (e) Tyagi, V.; Fasan, R. Angew. Chem., Int. Ed. 2016, 55,
2512–2516. (f) Khaskin, E.; Milstein, D. Chem. Commun. 2015, 51,
9002–9005.
(4) Catalytic (azaꢀ) Wittig reactions: (a) Marsden, S. P. Nat. Chem.
2009, 1, 685–687. Selected recent examples: (b) Wang, L.; Wang, Y.;
Chen, M.; Ding, M.ꢀW. Adv. Synth. Catal. 2014, 356, 1098–1104. (c)
Coyle, E. E.; Doonan, B. J.; Holohan, A. J.; Walsh, K. A.; Lavigne,
F.; Krenske, E. H.; O’Brien, C. J. Angew. Chem., Int. Ed. 2014, 53,
12907–12911. (d) Werner, T.; Hoffmann, M.; Deshmukh, S. Eur. J.
Org. Chem. 2014, 6630–6633. (e) Werner, T.; Hoffmann, M.;
Deshmukh, S. Eur. J. Org. Chem. 2014, 6873–6876. (f) Hoffmann,
M.; Deshmukh, S.; Werner, T. Eur. J. Org. Chem. 2015, 4532–4543.
ACS Paragon Plus Environment

Page 5 of 6
ACS Catalysis
Lin, S.; Oliver, P. A.; Peterson, M. J. J. Org. Chem. 1993, 58, 7286–
7288.
1
(15) We have recently reported 1a·HBr as a catalyst for carbon dioxꢀ
ide fixation, see: Toda, Y.; Komiyama, Y.; Kikuchi, A.; Suga, H. ACS
Catal. 2016, 6, 6906–6910. A modified procedure for the preparation
of 1a·HBr enables the purification without column chromatography.
See Supporting Information for details.
2
3
4
5
(16) (a) Gilheany, D. G. Chem. Rev. 1994, 94, 1339–1374. (b) Kayꢀ
ser, M. M.; Hatt, K. L.; Hooper, D. L. Can. J. Chem. 1991, 69, 1929–
1939. (c) Pauling, L. The nature of the chemical bond. 3rd ed.; Corꢀ
nell University Press: Ithaca, New York, 1960.
6
7
8
9
(17) VariableꢀTemperature 31P NMR experiments disclosed the equiꢀ
librium between ylide 1a and intermediate A, in which the intermediꢀ
ate can revert back to reactant 1a. The reaction of 1a and 2.5 equivaꢀ
lents of isobutyric anhydride in CDCl3 gave a 2:1 mixture of 1a and A
at 30 °C, and the ratio changed to 4:1 at 50 °C by rising temperature.
See Supporting Information for details.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(18) To assess the catalyst design on the reactivity and selectivity,
phosphonium salts with mꢀOH or pꢀOH, and an ammonium salt were
examined, and 1a·HBr gave the best result. See Supporting Inforꢀ
mation for details.
(19) DMAPꢀcatalyzed acylation of 4a afforded 5a in 60%, 6a in 6%,
and 7a in 28% yield within 15 min. Additionally, less than 60% conꢀ
version was observed in the absence of a catalyst (5a:6a = 90:10).
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 6
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment