Evaluating aryl esters as bench-stable C(1)-ammonium enolate precursors in catalytic, enantioselective Michael addition-lactonisations

Article abstract of DOI:10.1039/c9ob00703b

An evaluation of a range of aryl, alkyl and vinyl esters as prospective C(1)-ammonium enolate precursors in enantioselective Michael addition-lactonisation processes with (E)-trifluoromethylenones using isothiourea catalysis is reported. Electron deficient aryl esters are required for reactivity, with 2,4,6-trichlorophenyl esters providing optimal product yields. Catalyst screening showed that tetramisole was the most effective isothiourea catalyst, giving the desired dihydropyranone product in excellent yield and stereoselectivity (up to 90 : 10 dr and 98 : 2 er). The scope and limitations of this process have been evaluated, with a range of diester products being generated after ring-opening with MeOH to give stereodefined dihydropyranones with excellent stereocontrol (10 examples, typically ～90 : 10 dr and >95 : 5 er).

Full text of DOI:10.1039/c9ob00703b

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: C. M. Young, J. E.
Taylor and A. D. Smith, Org. Biomol. Chem., 2019, DOI: 10.1039/C9OB00703B.
This is an Accepted Manuscript, which has been through the
Volume 14 Number
1 7 January 2016 Pages 1–372
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
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
author guidelines.
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, outlined
in our author and reviewer resource centre, 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.
ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Page 1 of 5
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
View Article Online
DOI: 10.1039/C9OB00703B
Evaluating Aryl Esters as Bench-Stable C(1)-Ammonium Enolate
Precursors in Catalytic, Enantioselective Michael Addition-
Lactonisations
Received 00th January 20xx,
Accepted 00th January 20xx
Claire M. Young, James E. Taylor and Andrew D. Smith*
DOI: 10.1039/x0xx00000x
An evaluation of a range of aryl, alkyl and vinyl esters as prospective C(1)-ammonium enolate precursors in enantioselective
Michael addition-lactonisation processes with (E)-trifluoromethylenones using isothiourea catalysis is reported. Electron
deficient aryl esters are required for reactivity, with 2,4,6-trichlorophenyl esters providing optimal product yields. Catalyst
screening showed that tetramisole was the most effective isothiourea catalyst, giving the desired dihydropyranone product
in excellent yield and stereoselectivity (up to 90:10 dr and 98:2 er). The scope and limitations of this process have been
evaluated, with a range of diester products being generated after ring-opening with MeOH to give stereodefined
www.rsc.org/
~
dihydropyranones with excellent stereocontrol (10 examples, typically 90:10 dr and >95:5 er).
acids can be derivatised in situ through treatment with pivaloyl
chloride (1.5 equiv.) and i-Pr2NEt (4 equiv.) to generate a mixed
anhydride as an enolate precursor.[5] This protocol generates
dihydropyranone 2 in good yield and excellent stereoselectivity,
however the pivalic anhydride by-product is difficult to separate
from the desired product. This approach also relies on using an
excess of reagents to facilitate an efficient in situ activation
protocol. Bench-stable symmetric carboxylic anhydrides can
also be employed as C(1)-ammonium enolate precursors.[6] This
avoids the requirement for large excesses of additional reagents
and minimises side-product formation, although the protocol
formally requires two equivalents of the carboxylic acid
precursor, which could be a limitation when using complex or
expensive acid components. Acyl imidazoles can also be used in
isothiourea-catalysed Michael addition-lactonisation reactions,
under base-free conditions.[7] However, this process typically
requires high catalyst loadings (20 mol%) and long reaction
times to form the dihydropyranone products in slightly reduced
yields compared with acid precursors. Notably, the optimal
isothiourea catalyst varies with the enolate precursor, with
HyperBTM 3 favoured with both carboxylic acids and symmetric
anhydrides, while BTM·HCl 4·HCl is optimal when using acyl
imidazoles.
Introduction
C(1)-Ammonium enolates are valuable reactive intermediates
in a variety of diastereo- and enantioselective reactions
catalysed by chiral tertiary amine Lewis bases.[1] In early reports,
C(1)-ammonium enolates were generated by the interception
of an isolated di-substituted ketene or in situ-generated mono-
substituted ketene by a tertiary amine catalyst (Fig. 1).[2] More
recently, techniques have been developed to generate C(1)-
ammonium enolates in situ that avoid the use of highly reactive
ketenes. These processes rely upon derivatisation of bench-
stable carboxylic acids to generate reactive acylating agents
(such as mixed anhydrides) that readily react with tertiary
amine catalysts. Subsequent deprotonation of the resulting N-
acyl ammonium species generates the desired C(1)-ammonium
enolate (Fig. 1). Alongside other tertiary amine catalysts, chiral
isothioureas have been used extensively as efficient Lewis base
catalysts in a range of processes that proceed via an ammonium
enolate
enantioselective Michael addition-lactonisation process using
trifluoromethylenone to form stereodefined
intermediate.[3,4]
For
example,
a
model
1
dihydropyranones 2(Fig. 2a) has been investigated using a range
of C(1)-ammonium enolate precursors (Fig. 2b).[5,6,7] Carboxylic
Previous mechanistic and computational studies suggest that
the nature of the leaving group of the ammonium enolate
precursor is not only important for the initial catalyst acylation,
but that it is also required for deprotonation of the resulting N-
acyl ammonium.[5,8] When considering alternative ammonium
enolate processes at the carboxylic acid oxidation level it is
likely that the leaving group would also need to fulfil this dual
requirement. Electron deficient aryl esters are effective
acylating agents[9] and have been previously investigated as
C(1)-ammonium and -azolium enolate precursors.[10] Within the
field of isothiourea catalysis, aryl esters have been used for the
O
•
O
O
O
R1
R1
NR3
NR3
base
R1
NR3
X
NR3
R1
R2
R2
R2
X
R2
ketene
ammonium
enolate
acyl
ammonium
Figure 1: Strategies for ammonium enolate formation
EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St
Andrews, KY16 9ST, UK. E-mail: ads10@st-andrews.ac.uk.
† Electronic supplementary information (ESI) available: Experimental procedures, formation of α,β-acyl ammonium intermediates[11] and have
product characterisation data (mpt, NMR, IR, HRMS, [a]D, HPLC) and traces (NMR,
found particular utility in processes where the aryloxide leaving
HPLC) can be found at DOI: https://doi.org/10.17630/cb133261-b58e-4d72-b380-
c877c993dc5d[23]
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 5
ARTICLE
Journal Name
lactonisation reactions using trifluoromethylenones as model
a) Model Michael-Addition Lactonisation
View Article Online
electrophiles (Fig. 3).
DOI: 10.1039/C9OB00703B
O
O
Ph
NR3
O
Ph
Ph
NR3
O
Ph
+
Results and discussion
X
O
CF3
(i) Screening and Optimisation
2
Ph
CF3
1
Initially, the isothiourea-catalysed reaction between
trifluoromethylenone 1 and various potential ammonium
enolate precursors to form dihydropyranone 2 was studied. To
investigate the feasibility of alkyl esters as precursors,
b) Previous C(1) ammonium enolate precursors
Carboxylic Acids:[5]
Anhydrides:[6]
Acyl Imidazoles:[7]
O
O
O
Ph
trifluoroethyl ester
6 was subjected to representative
Ph
Ph
N
N
O
OH
conditions [(S)-5·HCl (20 mol%) and i-Pr2NEt (2.5 equiv.) in
CH2Cl2 at rt for 16 h]; while vinyl ester 7 was also evaluated due
to its known ability to act as an acyl transfer agent.[9] Both esters
gave < 5% conversion to product and were not evaluated
further (Table 1, Entries 1 and 2). To investigate if an electron-
deficient aryl ester was required, a number of electron-deficient
aryl (4-NO2C6H4, C6F5, 3,5-(CF3)2C6H3, 3,4,5-F3C6H2, 2,4,6-
Cl3C6H2) phenylacetic ester derivatives 8–12 were prepared
from phenylacetyl chloride and the requisite phenol, alongside
phenyl ester 13. The aryl esters were then screened in our
model reaction (Table 1, Entries 3–8). Electron deficient aryl
esters (8-12) gave the desired dihydropyranone in significant
yield (> 10%) (determined by NMR analysis of the crude material
using 1,4-dinitrobenzene as an internal standard) while phenyl
ester 13 gave no conversion.[19] Where significant yield was
observed, dihydropyranone 2 was generally formed in good dr
(> 84:16) and er (> 81:19) (Table 1, Entries 3–7). In particular,
trichlorophenyl ester 12 provided dihydropyranone 2 in good
63% yield along with a promising 84:16 dr and 87:13 er for the
major diastereoisomer (Table 1, Entry 7). This suggests that the
aryloxide generated following acylation of catalyst by ester 12
is both a sufficient leaving group for acyl ammonium formation
and a suitable base to promote ammonium enolate formation.
Notably, trichlorophenyl esters have also previously been found
to be optimal for methods in α,β-unsaturated acyl ammonium
catalysis, where the aryloxide is not required to operate as a
nucleophile.[11,20]
2
HyperBTM (5 mol%)
t-BuCOCl (1.5 equiv)
i-Pr2NEt (4 equiv)
CH2Cl2, –78 °C
2: 80%
HyperBTM (5 mol%)
i-Pr2NEt (1.25 equiv)
CH2Cl2, –78 °C
BTM·HCl (20 mol%)
MeCN (0.1 M), 0 °C
2: 81%
2: 68%
90:10 dr, > 99:1 er
94:6 dr, 99:1 er
91:9 dr, 97:3 er
 Readily available
 Excess reagents,
side-products
 Readily prepared
 Two equivalents
of acid required
 Mild acidic conditions
 Reduced reactivity
i-Pr
N
N
N
Ph
Ph
S
Ph
N
N
S
N
S
•HCl
HyperBTM
(2S,3R)-3
BTM
tetramisole•HCl
(R)-4
(S)-5•HCl
Figure 2: Ammonium enolate precursors in isothiourea-catalysed Michael
addition-lactonisation reactions.
group is subsequently required to act as a nucleophile to
facilitate catalyst turnover.[12] For example, 4-nitrophenyl esters
have been used as substrates in stereoselective [2,3]-
sigmatropic rearrangements,[13,8b] as well as enantioselective
additions to iminium ions[14] and in α,β-unsaturated acyl
ammonium catalysis.[15] Stable pentafluorophenyl esters have
also been used as ammonium enolate precursors in dual
catalytic α-functionalisation processes developed by the groups
of Snaddon,[16] Hartwig[17] and Gong.[18]
Further optimisation of the reaction with trichlorophenyl ester
12 was then investigated (Table 2).[21] First, the reaction
concentration was increased to 0.2 M resulting in a yield of 57%
of 2 in 5 h at RT with no significant reduction in diastereo- or
enantioselectivity (87:13 dr, 88:12 er) (Table 2, Entry 1). In the
absence of catalyst, only starting materials were recovered
(Table 2, Entry 2). Changing the solvent to THF improved the
product er (97:3) while maintaining a good yield (55%) (Table 2,
Entry 3). The use of BTM 4 as catalyst gave comparable results
to tetramisole·HCl 5·HCl (Table 2, Entry 4), while HyperBTM 3
gave a drop in both yield and enantioselectivity (Table 2, Entry
5). Changing the stoichiometry of auxiliary base and ester to 1
and 2 equivalents respectively and performing the reaction at 0
To date, the use of ester substrates in isothiourea-catalysed
formal [4+2] cycloaddition processes proceeding via an
ammonium enolate have yet to be explored. In this manuscript,
we report the investigation of various bench-stable esters as
C(1)-ammonium enolate precursors for Michael addition-
This work:
O
Ar1
Ar2
O
O
NR3
Ar1
Ph
O
+
Ar2
OR
CF3
CF3
R = aryl, alkyl,
vinyl
Figure 3: Esters as precursors in isothiourea-catalysed Michael addition-
lactonisation reactions.
°C over 16 h, gave dihydropyranone
2 with excellent
stereoselectivity (89:11 dr, 98:2 er) and in good yield (79%) as a
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 5
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
Table 1: Results of acylating agent screen.
Table 2: Reaction optimisation.
Cl Cl
View Article Online
DOI: 10.1039/C9OB00703B
O
O
O
Ph
Ph
Ph
(S)-5•HCl (20 mol%)
i-Pr2NEt (2.5 equiv.)
O
Ph
OR
O
O
Catalyst (mol%)
i-Pr2NEt (2.5 equiv.)
Solvent (0.2 M)
+
CF3
Cl
Ph
O
12
CH2Cl2 (0.1
16 h
M), RT
O
+
2
O
Ph
CF3
Ph
CF3
temp (°C), time (h)
1
Ph
CF3
2
1
Entry
R
Yield (%)a
drb
erc
Entry Solvent Temp. Time (h) Catalyst (%) Yield (%)a
drb
erc
1
2
3
4
5
6
7
8
CF3CH2 6
CH2=CH 7
4-NO2C6H4 8
C6F5 9
3,5-(CF3)2C6H3 10
3,4,5-F3C6H2 11
2,4,6-Cl3C6H2 12
C6H5 13
<5%
<5%
32
26
16
11
63
<5%
n/d
n/d
n/d
n/d
1
2
3
4
5
6d
7d
8d
CH2Cl2 RT
CH2Cl2 RT
5
5
5
5
5
16
48
48
5·HCl (20)
—
5·HCl (20)
4 (20)
53
0
87:13 88:12
n/d n/d
87:13
87:13
88:12
87:13
84:16
n/d
83:17
85:15
81:19
81:19
87:13
n/d
THF
THF
THF
THF
THF
THF
RT
RT
RT
0 °C
0 °C
0 °C
55
53
41
79e
96e
76e
84:16 97:3
86:14 4:96
88:12 10:90
89:11 98:2
89:11 98:2
91:9 95:5
3 (20)
5·HCl (20)
5·HCl (10)
5·HCl (5)
[a] Yield determined by 1H NMR spectroscopic analysis using 1,4-
dinitrobenzene as internal standard. [b] Determined by 1H NMR
spectroscopic analysis of the crude reaction mixture. [c] (3S,4S):(3R,4R).
Determined by chiral HPLC analysis.
[a] Unless stated, determined by 1H NMR spectroscopic analysis using 1,4-
dinitrobenzene as internal standard. [b] Determined by 1H NMR spectroscopic
analysis of the crude reaction mixture. [c] (3S,4S):(3R,4R). Determined by chiral
HPLC analysis. [d] i-Pr2NEt (1.0 equiv.), 12 (2.0 equiv.), [e] Isolated yield.
mixture of diastereoisomers (Table 2, Entry 6). Under these
conditions, the catalyst loading could be reduced to 10 mol%
without compromising the yield (96%) or stereoselectivity (dr
89:11, er 98:2) (Table 2, Entry 7). This yield and high
stereoselectivity compares favourably with those previously
reported for other C(1)-ammonium enolate precursors,
however, a long reaction time (48 h) was required. Attempts to
lower the catalyst loading to 5 mol% compromised the yield in
this case (Table 2, Entry 8).
a mixture of diastereoisomers in excellent 86% yield and 97:3 er
after the two-step protocol. Electron-withdrawing arylacetic
substituents on the ester were again well tolerated, with keto-
esters 17 (4-trifluoromethyl) and 18 (4-bromo) isolated in good
yields (77% and 73% respectively) and enantioselectivity (93:7
and 97:3 er respectively). Electron-donating substituents gave
mixed results with 4-methoxy substituted keto-ester 19 isolated
in 73% yield and 97:3 er, while incorporation of a more electron-
donating 4-dimethylamino group only gave moderate 51% yield
of 20 after prolonged reaction time (6 days, some 1 remaining)
however high er (99:1) was observed. A 2-naphthyl substituent
was also tolerated, giving keto-ester 21 in good 72% yield and
97:3 er. Variation of the substitution on the aryl group of the
enone was then explored (Table 3c). Again, the introduction of
electron withdrawing substituents was well tolerated with 4-
bromo 22 and 3-methoxy 23 substitution giving the
corresponding products in good yields (69% and 86%
respectively) and with high enantioselectivity (95:5 and 94:6 for
22 and 23 respectively). Substitution of the aryl ring with an
electron-donating group led to good yield of 4-Me 24 (62%) with
(ii) Scope and Limitations
Under the optimised conditions, the scope and limitations of
the process were explored using various trichlorophenyl
arylacetic esters and substituted trifluoromethylenones (Table
3). The crude dr of the reaction products was generally high
(around 90:10), while the products were isolated as an
inseparable mixture of diastereoisomers. The er of the major
diastereoisomer is reported in each case. Incorporation of a
strongly electron-withdrawing 4-trifluoromethyl substituent on
the arylacetic ester was well tolerated, giving dihydropyranone
14 in good yield (75%) and 90:10 er (Table 3a). An arylacetic
ester bearing an electron-donating 4-methoxy substituent gave
50% yield of dihydropyranone 15 in an excellent 95:5 er. The
scope was further explored, and the utility of the protocol
extended by carrying out in situ methanolysis of the
dihydropyranone products by addition of excess methanol after
the catalysis. The ring-opened methyl ester products were more
stable to column chromatography than the corresponding
dihydropyranones, leading to more consistent and
representative results (Table 3b). Keto-ester 16 was isolated as
high enantioselectivity (96:4 er). Finally,
a heterocycle-
substituted product 25 was also isolated in good yield (69%) and
excellent 98:2 er albeit it in a lower 71:29 crude dr.
Based upon our previous reports, a mechanism for this process
can be postulated. The reaction proceeds through initial
acylation of catalyst 5 by trichlorophenyl ester 12 to give acyl
ammonium
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Organic & Biomolecular Chemistry
Please do not adjust margins
Page 4 of 5
Journal Name
ARTICLE
View Article Online
DOI: 10.1039/C9OB00703B
Table 3: Substrate screen.
O
O
O
O
Ar
(S)-5•HCl (10 mol%)
i-Pr2NEt (1.0 equiv.)
THF (0.2 M)
(S)-5•HCl (10 mol%)
MeOH, RT
16 h
Ar
Ar
OAr
OMe
CF3
Ar
Ar
i-Pr2NEt (1.0 equiv.)
(2.0 equiv.)
O
O
THF (0.2 M)
+
O
Ar
CF3
Ar
CF3
O
Ar
CF3
a) Lactone products
b) Ring-opened products: Variation of ester
F3C Br
c) Ring-opened products: Variation of enone
O
O
O
O
O
O
Ph
O
Ph
Ph
OMe
MeO
OMe
CF3
OMe
OMe
OMe
Ph
CF3
Ph
2
Ph
Ph
96%
89:11 dr, 98:2 er
Br
O
CF3
O
O
CF3
O
CF3
O
CF3
F3C
O
16
17
18
22
23
86%
86%
77%
73%
69%
88:12 dr, 97:3 er 89:11 dr, 93:7 er
83:17 dr, 97:3 er
90:10 dr, 95:5 er
90:10 dr, 94:6 er
O
O
Ph
CF3 MeO
Me2N
OMe
O
O
O
Ph
14
75%
O
OMe
Ph
OMe
88:12 dr, 90:10 er
OMe
CF3
MeO
OMe
O
Ph
Ph
Ph
Me
O
CF3
O
O
O
CF3
O
CF3
O
O
CF3
Ph
CF3
15
19
20
21
24
25
50%
73%
51%
72%
62%
69%
90:10 dr, 95:5 er
94:6 dr, 97:3 er
dr n/d,[a] 99:1 er
92:8 dr, 97:3 er
89:11 dr, 96:4 er
71:29 dr, 98:2 er
Yields are the isolated yield for a mixture of diastereoisomers after purification. The reported dr is that of the crude material as determined by 1H NMR spectroscopic
analysis. The reported er is given for the major diastereomer (3S,4S):(3R,4R) as determined by chiral HPLC analysis. [a] dr could not be determined by 1H NMR
spectroscopic analysis of the crude material. dr of isolated 19 was 81:18.
ion pair 26.[5] Deprotonation by the aryloxide counter ion then moderate to excellent yield and up to excellent enantio- and
gives the favoured (Z)-ammonium enolate intermediate 27, diastereoselectivity.
which exhibits a syn-coplanar geometry due to a stabilising O···S
Scheme 1: Proposed catalytic cycle.
interaction.[22] Ammonium enolate 27 stereoselectively reacts
5•HCl
with enone 1 to give intermediate 28. Subsequent cyclisation
O
O
gives dihydropyranone 2 and regenerates catalyst 5.
Ph
Ph
Ph
O
N
OAr
Ph
12
N
5
S
Ar = 2,4,6-Cl3C6H2
CF3
Conclusions
2
In conclusion, electron deficient aryl esters are efficient
ammonium enolate precursors combining the properties of
being competent acylating agents and having a leaving group
that is a suitable base for ammonium enolate formation. In a
Michael addition-lactonisation with trifluoromethyl enones,
trichlorophenyl esters proved to be viable C(1)-ammonium
enolate precursors giving dihydropyranone products in good to
excellent yield and high enantio- and diastereoselectivity. In
contrast to other ammonium enolate precursors such as mixed
anhydrides, symmetric anhydrides or acyl imidazoles,
tetramisole 5·HCl proved to be the optimal isothiourea catalyst.
Subsequent in situ ring opening of dihydropyranones with
methanol led to a range of highly functionalised keto-esters in
N
O
N
Ph
Ph
Ph
O
N
S
N
S
OAr
F3C
O
Ph
Ph
28
26
OAr
N
O
Ph
N
S
O
iPr2NHEt
HOAr
iPr2NEt
OAr
Ph
CF3
1
27
Ph
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 4
Please do not adjust margins

Page 5 of 5
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
10 a) L. Hao, X. Chen, S. Chen, K. Jiang, J. Torres andVYie.wRA.rCtichlei,OOnrlinge.
Chem. Front., 2014, 1, 148; b) L. Hao, Y. Du, H. Lv, X. Chen, H.
Jiang, Y. Shao and Y. R. Chi, Org. Lett., D2O01I:21,01.1403, 92/1C594O.B00703B
11 A. Matviitsuk, J. E. Taylor, D. B. Cordes, A. M. Z. Slawin and
A. D. Smith, Chem. Eur. J., 2016, 22, 17748.
Conflicts of interest
There are no conflicts to declare.
12 For a review see: W. C. Hartley, T. J. C. O’Riordan and A. D.
Smith, Synthesis, 2017, 49, 3303.
Acknowledgements
13 a) T. H. West, D. S. B. Daniels, A. M. Z. Slawin and A. D. Smith,
J. Am. Chem. Soc., 2014, 136, 4476; b) T. H. West, S. S. M.
Spoehrle and A. D. Smith, Tetrahedron, 2017, 73, 4138; c) S. S.
M. Spoerhle, T. H. West, J. E. Taylor, A. M. Z. Slawin and A. D.
Smith, J. Am. Chem. Soc., 2017, 139, 11895; d) K. Kasten, A. M.
Z. Slawin and A. D. Smith, Org. Lett., 2017, 19, 5182.
14 J. N. Arokianathar, A. B. Frost, A. M. Z. Slawin, D. Stead and A.
D. Smith, ACS Catalysis, 2018, 8, 1153.
We thank the European Research Council under the European
Union’s Seventh Framework Programme (FP7/2007-2013) ERC
Grant Agreement no. 279850 (CMY, JET). ADS thanks the Royal
Society for a Wolfson Merit Award. We also thank the EPSRC
UK National Mass Spectrometry Facility at Swansea University.
15 A. Matviitsuk, M. D. Greenhalgh, D. -J. Barrios Antúnez, A. M.
Z. Slawin and A. D. Smith, Angew. Chem. Int. Ed., 2017, 56,
12282.
Notes and references
16 a) K. J. Schwarz, J. L. Amos, J. C. Klein, D. T. Do and T. N.
Snaddon, J. Am. Chem. Soc., 2016, 138, 5214; b) K. J. Schwarz,
C. M. Pearson, G. A. Contron-Rosada, P. Liu and T. N. Snaddon,
Angew. Chem. Int. Ed, 2018, 57, 7800; c) K. J. Schwarz, C. Yang,
J. W. B. Fyfe and T. N. Snaddon, Angew. Chem. Int. Ed, 2018,
57, 12102; d) L. Hutchings-Goetz, C. Yang and T. N. Snaddon,
ACS Catal., 2018, 8, 10537; e) W. R. Scaggs and T. N. Snaddon,
Chem. Eur. J. 2018, 24, 14378; f) J. W. B. Fyfe, O. M. Kabia, C.
M. Pearson and T. N. Snaddon, Tetrahedron, 2018, 74, 5383;
g). W. R. Scaggs, T. D. Scaggs and T. N. Snaddon, Org. Biomol.
Chem., 2019, 17, 1787.
1
For reviews of ammonium enolates see: a) M. J. Gaunt and C.
C. C. Johansson, Chem. Rev., 2007, 107, 5596; b) K. N. Van, L.
C. Morrill, A. D. Smith and D. Romo in Lewis Base Catalysis in
Organic Synthesis, ed.: E. Vedejs and S. E. Denmark, Wiley,
Hoboken, vol. 2, ch. 13, pp.527.
For selected examples see: a) R. Samtle and H. Pracejus, J.
Prakt. Chem., 1972, 314, 157; b) J. C. Sauer, J. Am. Chem. Soc.,
1947, 69, 2444; c) H. Wynberg and E. G. J. Staring, J. Am.
Chem. Soc., 1982, 104, 166.
2
3
4
a) For reviews, see: L. C. Morrill and A. D. Smith, Chem. Soc.
Rev., 2014, 43, 6214; b) J. Merad, J.-M. Pons, O. Chuzel and C.
Bressy, Eur. J. Org. Chem., 2016, 2016, 5589.
17 X. Jiang; J. J. Beiger and J. F. Hartwig, J. Am. Chem. Soc., 2017,
139, 87.
18 Aryl esters have been used in formal [3+2] cycloadditions: J.
Song, Z. -J. Zhang, S. -S. Chen, T. Fan and L. -Z. Gong, J. Am.
Chem. Soc., 2018, 140, 3177
For selected examples see: a) V. C. Purohit, A. S. Malta and D.
Romo, J. Am. Chem. Soc., 2008, 130, 10478; b) C. A. Leverett,
V. C. Purohit and D. Romo, Angew. Chem. Int. Ed., 49, 2010,
9479; c) D. Belmessieri, L. C. Morrill, C. Simal, A. M. Z. Slawin
and A. D. Smith, J. Am. Chem. Soc., 2011, 133, 2714; d) D.
Belmessieri, D. B. Cordes, A. M. Z. Slawin and A. D. Smith, Org.
Lett., 2013, 15, 3472; e) S. R. Smith, J. Douglas, H. Prevet, P.
Shapland, A. M. Z. Slawin and A. D. Smith, J. Org. Chem., 2014,
79, 1626.
19 Relative and absolute product configurations assigned by
reference to previous work[5]
20 M. D. Greenhalgh, S. Qu, A. M. Z. Slawin and A. D. Smith,
Chem. Sci., 2018, 9, 4909.
21 For full details see Supporting Information.
22 a) V. I. Minkin and R. M. Minyaev, Chem. Rev. 2001, 101, 1247;
b) Y. Nagao, T. Hirata, S Goto, S. Sano and A. Kakehi, J. Am.
Chem. Soc., 1998, 120, 3104; c) V. Birman, X. Li and Z. Han Org.
Lett., 2007, 9, 37 d) K. A. Brameld, B. Kuhn, D. C. Reuter and
M. Stahl, J. Chem. Inf. Model. 2008, 48, 1; e) P. Liu, X. Yang, V.
B. Birman and K. N. Houk, Org. Lett. 2012, 14, 3288; f) E. R. T.
Robinson, D. M. Walden, C. Fallan, M. D. Geenhalgh, P. H. -Y.
Cheong and A. D. Smith, Chem. Sci., 2016, 7, 6919 g) D. J.
Pascoe, K. B. Ling and S. L. Cockroft, J. Am. Chem. Soc., 2017,
139, 15160 h) M. D. Greenhalgh, S. M. Smith, D. M. Walden, J.
E. Taylor, Z. Brice, E. R. T. Robinson, C. Fallan, D. B. Cordes, A.
M. Z. Slawin, H. C. Richardson, M. A. Grove, P. H. -Y. Cheong
and A. D. Smith. Angew. Chem. Int. Ed., 2016, 7, 6919
23 The data underpinning this research can be found at DOI:
https://doi.org/10.17630/cb133261-b58e-4d72-b380-
c877c993dc5d
5
6
L. C. Morrill, J. Douglas, T. Lebl, A. M. Z. Slawin, D. J. Fox and
A. D. Smith, Chem. Sci., 2013, 4, 4146.
L. C. Morrill, L. A. Ledingham, J.-P. Couturier, J. Bickel, A. D.
Harper, C. Fallan and A. D. Smith, Org. Biomol. Chem., 2014,
12, 624.
7
8
C. M. Young, D. G. Stark, T. H. West, J. E. Taylor and A. D.
Smith, Angew. Chem. Int. Ed., 2016, 55, 14394.
For selected examples, see: a) K. Nakata, K. Gotoh, K. Ono, K.
Futami and I. Shiina, Org. Lett., 2013, 15, 1170; b) T. H. West,
D. M. Walden, J. E. Taylor, A. C. Brueckner, R. C. Johnson, P.
H.-Y. Cheong, G. C. Lloyd-Jones and A. D. Smith, J. Am. Chem.
Soc., 2017, 139, 4366.
J. E. Taylor and S. D. Bull, in Comprehensive Organic Synthesis
II, ed.: P. Knochel, Elsevier, Amsterdam, 2nd edn, 2014, vol. 6,
pp. 427.
9
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins