Gold-catalyzed reactions between alkenyldiazo carbonyl species and acetals

Article abstract of DOI:10.1021/jo400419d

In the presence of catalyst IPrAuSbF₆ catalyst (IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene), alkenyldiazo carbonyl species react with organic acetals to give E-configured alkyl 3,5-dimethoxy-5-pent-2- enoates stereoselectively. This rea

Full text of DOI:10.1021/jo400419d

Note
pubs.acs.org/joc
Gold-Catalyzed Reactions between Alkenyldiazo Carbonyl Species
and Acetals
Vinayak Vishnu Pagar, Appaso M. Jadhav, and Rai-Shung Liu*
Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan, ROC
S
* Supporting Information
ABSTRACT: In the presence of catalyst IPrAuSbF6 catalyst
(IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene), alkenyl-
diazo carbonyl species react with organic acetals to give E-
configured alkyl 3,5-dimethoxy-5-pent-2-enoates stereoselec-
tively. This reaction sequence comprises an initial Prins-type
reaction, followed by gold carbene formation.
lkenyldiazo carbonyl species are useful reagents to access
complicated acyclic and cyclic molecules.1 The major use
Table 1 shows the reactions between vinyldiazo ester 1a and
dimethoxymethylbenzene 6a using various acid catalysts. We
A
of these reagents relies on their initial diazo decomposition with
a metal catalyst to generate reactive alkenylmetal carbene
intermediates, further enabling stereo- or regioselective [3 + n]-
cycloadditions (n = 2−4) with suitable dipolarophiles.2−4 This
reaction route has found widespread applications to access
complicated carbo- and heterocyclic compounds.2−4 Alter-
natively, in the presence of suitable Lewis acid catalysts, these
alkenyl diazo reagent work as nucleophiles to react with
aldehydes and enones to give addition products to retain their
diazo functionalities.5 We recently reported6 formal [4 + 2]-
cycloadditions of these diazo species (1) with N-arylimines
(Povarov reaction)7 to give isolable diazo-containing cyclo-
adducts (3) using HOTf (3 mol %) or IPrAuCl/AgNTf2 (2.5
mol %, IPr = 1, 3-bis(diisopropylphenyl)imidazol-2-ylidene), as
depicted in eq 1. This reaction sequence is applicable also to
Table 1. Catalyst Screenings over Various Acid Catalysts
compounds
b
(yield, %)
entry
catalyst (mol %)
time (h)
1a
7a
1
IPrAuCl/AgNTf2 (2.5)
IPrAuCl/AgSbF6 (2.5)
IPrAuCl/AgSbF6 (2.5)
LAuCl/AgSbF6 (2.5)
PPh3AuCl/AgSbF6 (5)
AgSbF6 (2.5)
0.1
0.1
1.0
0.1
0.3
0.3
1.2
1.5
2.0
2.5
6.0
6.0
6.0
80
c
2
84 (81)
d
3
77
4
67
57
46
5
6
7
Rh2(OAc)4 (2.5)
Cu(OTf)2 (5)
8
9
Zn(OTf)2 (5)
10
11
12
13
HOTf (3)
Sc(OTf)3 (5)
46
51
76
In(OTf)3 (5)
HOTf (2)/PhCH(NH2)Me(3)
a
1a (1.0 equiv, 0.50 M), 6a (1.0 equiv), IPr = 1,3-bis-
(diisopropylphenyl)imidazol-2-ylidene, L = P(t-Bu)2(o-biphenyl).
Product yields are given after purification from a silica column.
b
c
The value in parentheses corresponds to a prior removal of AgCl.
d
this reaction was operated at 1.0 g scale with 0.1 M.
first tested the reactions with IPrAuCl/AgX (2.5 mol %, X =
NTf2 and SbF6) that were found to be chemoselective toward
the Povarov reaction6,7 of vinyldiazo species 1a (see eq 1).
Herein, we obtained ethyl 3,5-dimethoxy-5-pent-2-enoate 7a in
80−84% yields (entries 1 and 2). With IPrAuCl/AgSbF6, the
yield of compound 7a was kept at 81% with a prior filtration of
diphenoxymethylbenzenes (4) to effect an unprecedented oxa-
Povarov reaction, further affording oxacyclic products (5)
stereoselectively (eq 2).6 In this work, we report a distinct and
new route between alkenyldiazo carbonyl species 1 and
commonly used acetal substrates 6; this process generates
1,3-dialkoxy-4-diazo intermediate I, further giving E-configured
ethyl 3,5-dimethoxy-5-pent-2-enoate 7 stereoselectively (eq 3).
Received: February 28, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo400419d | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Table 2. Reaction Scope with Various Acetal Substrates
a
Product yields are given after purification from a silica column.
AgCl through a Celite bed. If the reaction was operated with
diazo reagent 1a (0.1 M) on a gram scale, the desired 7a was
obtained with 77% yield (entry 3). Other gold catalysts LAuCl/
AgSbF6 (L = P(t-Bu)2(o-biphenyl)) and PPh3AuCl/AgSbF6
appear to be less productive, giving desired unsaturated ester 7a
in 57−67% yields (entries 4 and 5). The use of AgSbF6 alone
gave ester 7a in 46% yield (entry 6). Other catalysts
Rh2(OAc)4, Cu(OTf)2, Zn(OTf)2, and HOTf, each at 2.5−5
mol % loading (entries 7−10), gave a complicated mixture of
products whereas Sc(OTf)3, In(OTf)3, and HOTf/PhCH-
(NH2)Me led to recovery of vinyldiazo species 1a in large
proportions (46−76%, entries 11−13). The E-configuration of
ester 7a is inferred from the X-ray diffraction8 of its acid
derivative 7a′, which was obtained by LiOH-catalyzed
hydrolysis in a THF/H2O (2:1) solution.
Table 2 shows the scope of this gold-catalyzed reaction with
various acetals 6b−p. The reaction is applicable to acetals 6b-6c
bearing various alkoxy groups (R = Et; allyl), giving desired
unsaturated esters 7b and 7c in 63% and 57% yields,
respectively. The scope of the reaction is expanded with its
applicability to phenyldimethoxymethanes 6d−g bearing
various phenyl substituents including electron-rich 4-methyl,
4-tert-butyl, 4-methoxy, and 2-methoxy, affording desired
unsaturated esters 7d−g in good yields (73−89%, entries 3−
6). The same reactions worked well with electron-deficient
phenyl substrates 6h and 6i bearing 4-chloro and 4-bromo
substituents, giving the expected products 7h and 7i in 74% and
78% yields, respectively (entries 7 and 8). We also tested the
reactions on heteroaryl substrates 6j−n including 3-furanyl, 3-
thienyl, 2-benzofuranyl, 3-indolyl, and 2-benzothienyl; their
corresponding products 7j−n had 67−77% yields (entries 9−
13). We tested the reactions on alkenyl acetals 6o and 6p to
provide unsaturated esters 7o and 7p in 86−87% yields (entries
14 and 15).
To expand the reaction scope, we also prepared various
diazovinyl carbonyl reagents 1b−g; the results are provided in
Table 3. As shown in entries 1−3, the reactions between
various vinyldiazo esters 1b−d and acetal 6a proceeded
smoothly to afford desired unsaturated esters 8b−d (X =
OtBu), Oallyl, OBn) in 72−82% yields, respectively. The same
reactions were applicable to vinyldiazo ketones 1e−g (X = nPr,
B
dx.doi.org/10.1021/jo400419d | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Table 3. Reaction Scope with Various Vinyldiazo Substrates
Scheme 2
carbocation by daizo functionality as in intermediate B. The
postulated carbene intermediate D is supported by a 1,2-
hydrogen shift11,12 in the deuterium labeling experiment
(Scheme 1). The excellent E-selectivity in this 1,2-shift is
indicative also of gold carbene species11,13 whereas the Z-
selectivity is known for rhodium carbenes.12,13
In summary, gold-catalyzed reactions between vinyldiazo
carbonyl species and acetals are described; the resulting E-
configured alkyl 3,5-dimethoxy-5-pent-2- enoates are obtained
in good yields. According to our experimental data, this
reaction sequence comprises an initial Prins-type reaction,
followed by gold-carbene generation. The success of this Prins-
type reaction indicates a stabilization effect of the diazo
functionality on the adjacent carbocation; this information
allows new designs between alkenyldiazo species and other
electrophiles.
2-thienyl, phenyl), giving unsaturated ketones 8e−g in
satisfactory yields (72−86%).
Shown in Scheme 1 are additional experiments undertaken to
understand the reaction mechanism. We prepared deuterated
Scheme 1
EXPERIMENTAL SECTION
■
General Comments. Unless otherwise noted, all reactions to
prepare the substrates were performed in oven-dried glassware under
nitrogen atmosphere with freshly distilled solvents. The catalytic
reactions were performed under nitrogen atmosphere. DCE, DCM,
and CH3CN were distilled from CaH2 under nitrogen. THF were
distilled from Na metal under nitrogen. All other commercial reagents
1
were used without further purification, unless otherwise indicated. H
and 13C NMR spectra were recorded on spectrometers 400, 500, and
600 MHz using chloroform-d1 (CDCl3), and dimethyl sulfoxide-d6
(DMSO) as internal standards. Alkenyldiazo compounds (1a−g) were
prepared according to literature references.4a,6,14
sample d1-1a with its alkenyl C(2)-proton fully deuterated; its
gold-catalyzed reaction with phenyldimethoxymethane d0-6a
gave the desired d1-7a bearing a fully deuterated CDCO2Et,
indicative of a 1,2-hydrogen shift. We performed the same
reaction using acetals d6-6a and do-6f in equimolar proportions,
their reactions with vinyldiazo ester 1a (2 equiv) gave
unsaturated esters d3-7a and d3-7f in 76% and 78% yields,
respectively. The two methoxy groups of each product
contained 50% deuterium content at the benzyl and alkenyl
General Procedure for the Gold-Catalyzed Reaction
between Acetal (6a) and Vinyldiazo Ester (1a). A dichloroethane
(DCE, 1.0 mL) solution of IPrAuCl (7.8 mg, 0.012 mmol) and
AgSbF6 (4.3 mg, 0.012 mmol) was stirred at 25 °C for 5 min, and to
this solution was added a DCE (1.5 mL) solution of alkenyl
diazoacetates (1a) (70 mg, 0.50 mmol) and acetal (6a) (76 mg, 0.50
mmol) over 5 min. The resulting solution was stirred at 25 °C. After
10 min, the solution was filtered over a short silica bed; the solvent was
evaporated under reduced pressure. The residue was purified on a flash
silica gel column (hexane/ethyl acetate = 9/1) to give compound 7a as
a colorless liquid (110 mg, 84% yield).
(E)-Ethyl 3,5-dimethoxy-5-phenylpent-2-enoate (7a): color-
less liquid (110 mg, 84%); 1H NMR (600 MHz, CDCl3) δ 7.34−7.29
(m, 4H), 7.23 (t, J = 7.0 Hz, 1H), 5.00 (s, 1H), 4.51 (dd, J = 5.3, 8.7
Hz, 1H), 4.11 (q, J = 7.0 Hz, 2H), 3.55 (s, 3H), 3.19 (s, 3H), 3.16 (dd,
J = 5.2, 13.6 Hz, 1H), 3.07 (dd, J = 5.3, 13.6 Hz, 1H), 1.24 (t, J = 7.1
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.0, 167.3, 141.4, 128.2,
127.5, 126.6, 91.9, 81.9, 59.3, 56.9, 55.5, 40.8, 14.4; HRMS calcd for
C15H20O4 264.1362, found 264.1362.
1
positions according to H NMR analysis whereas their mass
spectra revealed a 1:2:1 ratio, corresponding to the ratios of
d0:d3:d6 samples. Notably, the d0:d3:d6 ratio remains the same
even though diazo reagent 1a was absent. This information
confirms an intermolecular gold-catalyzed exchange of methoxy
between two acetals to give d3-6a and d3-6f before their
reactions with diazo species 1a.
Scheme 2 shows a plausible mechanism involving the
intermediacy of gold carbene species D. As IPrAuSbF6 enables
a rapid methoxy exchange between two acetals, as shown in
Scheme 1, this observation indicates a facile formation of the
oxonium intermediate A. We envisage that gold activates a
Prins-type reaction9,10 between vinyldiazo ester 1a and acetal
6a to generate 1,3-dimethoxy-4-diazo ester C; the success of
this reaction relies on the stabilization of an adjacent
Deuterated (E)-ethyl 3,5-dimethoxy-5-phenylpent-2-enoate
(d1-7a): colorless liquid (91 mg,70%); 1H NMR (600 MHz, CDCl3) δ
7.34−7.29 (m, 4H), 7.23 (d, J = 7.1 Hz, 1H), 4.51 (dd, J = 5.4, 8.7 Hz,
1H), 4.11 (q, J = 7.1 Hz, 2H), 3.59 (s, 3H), 3.20−3.15 (m, 4H), 3.08
(dd, J = 5.5, 13.4 Hz, 1H), 1.24 (t, J = 7.1 Hz, 3H); 13C NMR (150
C
dx.doi.org/10.1021/jo400419d | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
MHz, CDCl3) δ 172.9, 167.3, 141.4, 128.2, 127.5, 126.7, 91.7 (t, J = 24
Hz), 81.9, 59.3, 56.9, 55.5, 40.8, 14.4; HRMS calcd for C15H19DO4
265.1424, found 265.1428.
CDCl3) δ 173.1, 167.4, 159.0, 133.4 (d, J = 5.1 Hz), 127.0, 113.5, 91.8
(d, J = 6 Hz), 81.4 (d, J = 15.3 Hz), 59.4, 56.6, 55.5, 55.2, 40.7, 14.4;
HRMS calcd for C16H22O5 294.1467, found 294.1473, 297.1641,
300.1809.
(E)-Ethyl 3,5-dimethoxy-5-(2-methoxyphenyl)pent-2-enoate
(7g): light yellow liquid; (107 mg, 73%); 1H NMR (600 MHz,
CDCl3) δ 7.39 (d, J = 7.5 Hz, 1H), 7.19 (t, J = 7.8 Hz, 1H), 6.93 (t, J =
7.4 Hz, 1H), 6.81 (d, J = 8.1 Hz, 1H), 4.99 (s, 1H), 4.96 (dd, J = 5.1,
8.7 Hz, 1H), 4.07 (q, J = 7.1 Hz, 2H), 3.78 (s, 3H), 3.57 (s, 3H), 3.49
(dd, J = 5.1, 14.0 Hz, 1H), 3.19 (s, 3H), 2.90 (dd, J = 5.1, 14.0 Hz,
1H), 1.21 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.7,
167.3, 157.0, 129.5, 128.2, 127.1, 120.6, 110.1, 92.1, 74.9, 59.2, 56.8,
55.3, 55.2, 38.4, 14.3; HRMS calcd for C16H22O5 294.1467, found
294.1436.
Deuterated (E)-ethyl 3,5-dimethoxy-5-phenylpent-2-enoate
(d3-7a): colorless liquid (101 mg, 76%) ; 1H NMR (600 MHz,
CDCl3) δ 7.35−7.29 (m, 4H), 7.23 (t, J = 7.1 Hz, 1H), 5.00 (d, J = 3.4
Hz, 1H), 4.51 (dd, J = 5.2, 8.7 Hz, 1H), 4.11 (q, J = 7.2 Hz, 2H), 3.56
(s, 1.5H), 3.19 (s, 1.47 H), 3.15 (dd, J = 8.7, 13.5 Hz, 1H), 3.08 (dd, J
= 5.3, 13.5 Hz, 1H), 1.25 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 173.0, 167.4, 141.4 (d, J = 4.8 Hz), 128.2, 127.5, 126.6, 91.9
(d, J = 6.3 Hz), 81.9 (J = 15.1 Hz), 59.3, 56.9, 55.5, 40.8, 14.4; HRMS
calcd for C15H20O4 264.1362, found 264.1373, 267.1552, 270.1739.
(E)-Ethyl 3,5-dimethoxy-5-phenylpent-2-enoate (7a′): white
1
solid (56 mg, 90%); H NMR (500 MHz, CDCl3) δ 7.33 (d, J = 7.5
Hz, 2H), 7.31−7.24 (m, 3H) 4.96 (s, 1H), 4.45 (t, J = 8.5 Hz, 1H),
3.49 (s, 3H), 3.20 (dd, J = 8.0, 14.0 Hz, 1H), 3.06 (s, 3H), 2.95 (dd, J
= 6.5, 14.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 171.4, 168.0,
141.2, 128.2, 127.5, 126.4, 92.7, 81.0, 56.1, 55.4, 39.1; HRMS calcd for
C13H16O4 236.1049, found 236.1055.
(E)-Ethyl 5-(4-chlorophenyl)-3,5-dimethoxypent-2-enoate
1
(7h): yellow liquid (110 mg, 74%); H NMR (600 MHz, CDCl3) δ
7.27−7.26 (m, 4H), 5.00 (s, 1H), 4.48 (dd, J = 5.9, 8.1 Hz, 1H), 4.10
(q, J = 7.1 Hz, 2H), 3.55 (s, 3H), 3.18 (s, 3H), 3.10−3.08 (m, 2H),
1.24 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.6, 167.3,
139.9, 133.2, 128.4, 128.0, 92.0, 81.3, 59.4, 56.9, 55.5, 40.7, 14.2;
HRMS calcd for C15H19ClO4 298.0972, found 298.0973.
(E)-Ethyl 3,5-diethoxy-5-phenylpent-2-enoate (7b): light
1
yellow liquid (91 mg, 63%); H NMR (600 MHz, CDCl3) δ 7.32
(E)-Ethyl 5-(4-bromophenyl)-3,5-dimethoxypent-2-enoate
(d, J = 7.8 Hz, 2H), 7.28 (t, J = 8.2 Hz, 2H), 7.22 (d, J = 7.2 Hz, 1H),
4.93 (s, 1H), 4.60 (dd, J = 6.4, 7.9 Hz, 1H), 4.10 (q, J = 7.1 Hz, 2H),
3.71 (q, J = 7.0 Hz, 1H), 3.62 (q, J = 7.0 Hz, 1H), 3.39−3.32 (m, 2H),
3.26 (dd, J = 8.0, 13.2 Hz, 1H), 3.00 (dd, J = 6.3, 13.3 Hz, 1H), 1.24 (t,
J = 7.1 Hz, 3H), 1.16 (t, J = 7.0 Hz, 3H), 1.12 (t, J = 7.0 Hz, 3H); 13C
NMR (150 MHz, CDCl3) δ 172.2, 167.5, 142.1, 128.0, 127.3, 126.7,
92.1, 79.5, 64.2, 63.7, 59.3, 40.9, 15.3, 14.4, 14.0; HRMS calcd for
C17H24O4 292.1675, found 292.1668.
(E)-Ethyl 3,5-bis(allyloxy)-5-phenylpent-2-enoate (7c): light
yellow liquid (90 mg, 57%); 1H NMR (600 MHz, CDCl3) δ 7.34 (d, J
= 7.0 Hz, 2H), 7.30 (t, J = 7.3 Hz, 2H), 7.23 (d, J = 7.2 Hz, 1H),
5.84−5.78 (m, 2H), 5.27−5.09 (m, 4H), 4.98 (s, 1H), 4.68 (dd, J =
5.9, 8.4 Hz, 1H), 4.22−4.18 (m, 2H), 4.11 (q, J = 7.1 Hz, 2H), 3.90
(dd, J = 4.9, 13.0 Hz, 1H), 3.74 (dd, J = 5.8, 13.0 Hz, 1H), 3.34 (dd, J
= 8.4, 13.5 Hz, 1H), 3.05 (dd, J = 5.9, 13.5 Hz, 1H), 1.24 (t, J = 7.1
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 171.5, 167.3, 141.5, 134.9,
131.8, 128.2, 127.5, 126.8, 118.1, 116.3, 93.0, 79.3, 69.5, 68.9, 59.4,
40.7, 14.4; HRMS calcd for C19H24O4 316.1675, found 316.1668.
(E)-Ethyl 3,5-dimethoxy-5-p-tolylpent-2-enoate (7d): color-
less liquid (123 mg, 89%); 1H NMR (600 MHz, CDCl3) δ 7.23 (d, J =
8.0 Hz, 2H), 7.12 (d, J = 7.8 Hz, 2H), 5.01 (s, 1H), 4.49 (dd, J = 5.2,
8.7 Hz, 1H), 4.12 (q, J = 7.1 Hz, 2H), 3.57 (s, 3H), 3.18 (s, 3H), 3.15
(dd, J = 5.2, 13.5 Hz, 1H), 3.07 (dd, J = 5.2, 13.5 Hz, 1H), 2.31 (s,
3H), 1.25 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.1,
167.4, 138.3, 137.1, 128.9, 126.5, 91.8, 81.7, 59.3, 56.8, 55.5, 40.8, 21.1,
14.4; HRMS calcd for C16H22O4 278.1518, found 278.1518.
(E)-Ethyl 5-(4-tert-butylphenyl)-3,5dimethoxypent-2-enoate
(7e): light yellow liquid (137 mg, 86%) ; 1H NMR (600 MHz, CDCl3)
δ 7.32 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.3 Hz, 2H), 5.01 (s, 1H), 4.48
(dd, J = 5.3, 8.7 Hz, 1H), 4.12 (q, J = 7.1 Hz, 2H), 3.57 (s, 3H), 3.19
(s, 3H), 3.14 (dd, J = 5.1, 13.5 Hz, 1H), 3.06 (dd, J = 5.1, 13.5 Hz,
1H), 1.28 (s, 9H), 1.24 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 173.3, 167.4, 150.4, 138.4, 126.3, 125.4, 91.8, 81.7, 59.4,
56.9, 55.5, 40.9, 33.8, 31.3, 14.4; HRMS calcd for C19H28O4 320.1988,
found 320.1993
(E)-Ethyl 3,5-dimethoxy-5-(4-methoxyphenyl)pent-2-enoate
(7f): light yellow liquid (130 mg, 89%); 1H NMR (600 MHz, CDCl3)
δ 7.25 (d, J = 8.3 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 4.98 (s, 1H), 4.46
(dd, J = 5.5, 8.5 Hz, 1H), 4.11 (q, J = 7.0 Hz, 2H), 3.77 (s, 3H), 3.54
(s, 3H), 3.16−3.13 (m, 4H), 3.06 (dd, J = 5.5, 13.5 Hz, 1H), 1.23 (t, J
= 7.0 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.0, 167.3, 159.0,
133.4, 127.8, 113.5, 91.9, 81.4, 59.3, 56.6, 55.4, 55.1, 40.7, 14.3; HRMS
calcd for C16H22O5 294.1467, found 294.1436.
1
(7i): yellow liquid (133 mg, 78%); H NMR (600 MHz, CDCl3) δ
7.42 (d, J = 8.8 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 5.00 (s, 1H), 4.47
(dd, J = 5.2, 8.7 Hz, 1H), 4.10 (q, J = 7.1 Hz, 2H), 3.56 (s, 3H), 3.18
(s, 3H), 3.08 (dd, J = 1.7, 7.9 Hz, 2H), 1.24 (t, J = 7.1 Hz, 3H); 13C
NMR (150 MHz, CDCl3) δ 172.6, 167.3, 140.4, 131.4, 128.4, 121.4,
92.1, 81.4, 59.5, 56.9, 55.5, 40.7, 14.4; HRMS calcd for C15H19BrO4
342.0467, found 342.0461.
(E)-Ethyl 5-(furan-3-yl)-3,5-dimethoxypent-2-enoate (7j):
1
light yellow liquid (91 mg, 72%); H NMR (600 MHz, CDCl3) δ
7.35 (d, J = 3.6 Hz, 1H), 7.34 (d, J = 3.5 Hz, 1H), 6.41 (s, 1H), 5.01
(s, 1H), 4.53 (dd, J = 6.0, 8.2 Hz, 1H), 4.12 (q, J = 7.2 Hz, 2H), 3.57
(s, 3H), 3.25 (dd, J = 5.2, 13.5 Hz, 1H), 3.22 (s, 3H), 3.11 (dd, J = 6.0,
13.5 Hz, 1H), 1.24 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3)
δ 172.7, 167.4, 143.1, 140.1, 125.3, 108.9, 92.1, 73.7, 59.4, 56.3, 55.5,
38.9, 14.4; HRMS calcd for C13H18O5 254.1154, found 254.1145.
(E)-Ethyl 3,5-dimethoxy-5-(thiophen-3-yl)pent-2-enoate
(7k): light yellow liquid (103 mg, 77%); 1H NMR (600 MHz,
CDCl3) δ 7.24 (dd, J = 3.0, 5.1 Hz, 1H), 7.16 (d, J = 2.9 Hz, 1H), 7.08
(d, J = 5.9 Hz, 1H), 5.00 (s, 1H), 4.63 (dd, J = 5.7, 8.4 Hz, 1H), 4.11
(q, J = 7.2 Hz, 2H), 3.55 (s, 3H), 3.24−3.20 (m, 4H), 3.11 (dd, J = 5.8,
13.6 Hz, 1H), 1.24 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3)
δ 172.8, 167.3, 142.7, 126.1, 125.6, 121.8, 91.9, 77.6, 59.4, 56.7, 55.5,
39.8, 14.4; HRMS calcd for C13H18O4S 270.0926, found 270.0922.
(E)-Ethyl 5-(benzofuran-3-yl)-3,5-dimethoxypent-2-enoate
(7l): light yellow liquid (101 mg, 67%); 1H NMR (500 MHz,
CDCl3) δ 7.51 (d, J = 7.5 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.23 (t, J
= 7.5 Hz, 1H), 7.18 (t, J = 7.5 Hz, 1H), 6.67 (s, 1H), 5.05 (s, 1H), 4.73
(dd, J = 6.0, 8.5 Hz, 1H), 4.12 (q, J = 7.5 Hz, 2H), 3.55−3.51 (m,4H),
3.31 (s, 3H), 3.22 (dd, J = 6.0, 14.0 Hz, 1H), 1.24 (t, J = 7.5 Hz, 3H);
13C NMR (125 MHz, CDCl3) δ 171.8, 167.3, 156.3, 155.0, 127.9,
124.1, 122.6, 120.9, 111.4,104.6, 92.4, 74.8, 59.5, 56.9, 55.6, 36.9, 14.3;
HRMS calcd for C17H20O5 304.1311, found 304.1302.
(E)-Ethyl 3,5-dimethoxy-5-(1-tosyl-1H-indol-3-yl)pent-2-
enoate (7m): yellow semisolid (231 mg, 71%); 1H NMR (600
MHz, CDCl3) δ 7.92 (d, J = 8.3 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H),
7.71 (d, J = 8.3 Hz, 2H), 7.50 (s, 1H), 7.27 (t, J = 7.8 Hz, 1H), 7.22−
7.17 (m, 3H), 4.99 (s, 1H), 4.44 (dd, J = 5.2, 8.6 Hz, 1H), 4.09 (q, J =
7.1 Hz, 2H), 3.47 (s, 3H), 3.42 (dd, J = 8.3, 13.5 Hz, 1H), 3.30 (s,
3H), 3.17 (dd, J = 6.0, 13.5 Hz, 1H), 2.20 (s, 3H), 1.22 (t, J = 7.1 Hz,
3H); 13C NMR (150 MHz, CDCl3) δ 172.3, 167.3, 144.8, 135.4,
135.2, 129.8, 129.2, 126.7, 124.7, 123.9, 123.2, 122.6, 120.9, 113.5,
92.2, 74.9, 59.5, 56.6, 55.4, 38.4, 21.5, 14.3; HRMS calcd for
C24H27NO6S 457.1559, found 457.1571.
(E)-Ethyl 5-(benzo[b]thiophene-3-yl)-3,5-dimethoxypent-2-
enoate (7n): light yellow liquid (118 mg, 74%); 1H NMR (600
MHz, CDCl3) δ 7.79 (d, J = 7.8 Hz, 1H), 7.69 (d, J = 8.2 Hz, 1H),
7.30−7.26 (m, 2H), 7.21 (s, 1H), 5.05 (s, 1H), 4.88 (dd, J = 5.6, 8.4
Hz, 1H), 4.12 (q, J = 7.1 Hz, 2H), 3.57 (s, 3H), 3.35 (dd, J = 5.2, 13.7
Deuterated (E)-ethyl 3,5-dimethoxy-5-(4-methoxyphenyl)-
1
pent-2-enoate (d3-7f): light yellow liquid (113 mg, 78%); H NMR
(600 MHz, CDCl3) δ 7.26−7.24 (m, 2H), 6.84 (d, J = 8.6 Hz, 2H),
4.99 (d, J = 3.4 Hz, 1H), 4.46 (dd, J = 5.5, 8.5 Hz, 1H), 4.11 (q, J = 7.1
Hz, 2H), 3.77 (s, 3H), 3.55 (s, 1.5H), 3.16−3.13 (m, 2.5H), 3.06 (dd,
J = 5.4, 13.5 Hz, 1H), 1.24 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz,
D
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Note
Hz, 1H), 3.30 (s, 3H), 3.24 (dd, J = 5.6, 13.6 Hz, 1H), 1.24 (t, J = 7.1
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.1, 167.3, 146.3, 139.7,
139.4, 124.0 (CH × 2), 123.3, 122.5, 121.7, 92.3, 77.9, 59.5, 56.9, 55.5,
40.7, 14.3; HRMS calcd for C17H20O4S 320.1082, found 320.1091.
(2E,6E)-Ethyl 3,5-dimethoxy-7-phenylhepta-2,6-dienoate
(7o): light yellow liquid (124.7 mg, 86%); 1H NMR (600 MHz,
CDCl3) δ 7.36 (d, J = 7.3 Hz, 2H), 7.28 (t, J = 7.4 Hz, 2H), 7.21 (d, J
= 7.3 Hz, 1H), 6.51 (d, J = 15.9 Hz, 1H), 6.09 (dd, J = 7.9, 15.9 Hz,
1H), 5.03 (s, 1H), 4.13−4.07 (m, 3H), 3.58 (s, 3H), 3.30 (s, 3H), 3.16
(dd, J = 7.4, 13.2 Hz, 1H),), 3.01 (dd, J = 6.6, 13.2 Hz, 1H), 1.24 (t, J
= 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.5, 167.3, 136.5,
132.1, 129.4, 128.4, 127.6, 126.4, 92.2, 80.5, 59.3, 56.4, 55.4, 38.3, 14.3;
HRMS calcd for C17H22O4 290.1518, found 290.1515.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of compounds 7a−p, d1-7a, d3-7a,
d3-7f, 8b−g, and crystallographic data for compound 7a′. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: rsliu@mx.nthu.edu.tw.
Notes
■
(2E,6E)-Ethyl 3,5-Dimethoxy-7-(thiophene-2-yl)hepta-2,6-di-
enoate (7p): light yellow liquid (128 mg, 87%); 1H NMR (600 MHz,
CDCl3) δ 7.12 (dd, J = 4.1,2.5 Hz, 1H), 6.92 (t, J = 1.5 Hz, 2H), 6.64
(d, J = 15.7 Hz, 1H), 5.92 (dd, J = 7.8,15.7 Hz, 1H), 5.03 (s, 1H),
4.11(q, J = 7.2 Hz, 2H), 4.03(q, J = 6.7 Hz, 1H), 3.59 (s, 3H), 3.29 (s,
3H), 3.14 (dd, J = 7.5, 13.2 Hz, 1H),), 2.96 (dd, J = 6.4, 13.2 Hz, 1H),
1.24 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.5, 167.4,
141.8, 129.1, 127.3, 125.7, 125.1, 124.3, 92.2, 80.2, 59.4, 56.5, 55.5,
38.3, 14.3; HRMS calcd for C15H20O4S 296.1082, found 296.1081.
(E)-tert-Butyl 3,5-dimethoxy-5-phenylpent-2-enoate (8b):
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank National Science Council, Taiwan, for financial
support of this work.
REFERENCES
■
(1) Selected reviews: (a) Doyle, M. P.; McKervy, M. A.; Ye, T.
Modern Catalytic Methods for Organic Synthesis with Diazo Compounds;
John Wiley & Sons: New York, 1998. (b) Padwa, A.; Weingarten, M.
D. Chem. Rev. 1996, 96, 223. (c) Davies, H. M. L.; Denton, J. R. Chem.
Soc. Rev. 2009, 38, 3061. (d) Doyle, M. P.; Duffy, R.; Ratnikov, M.;
Zhou, L. Chem. Rev. 2010, 110, 704. (e) Davies, H. M. L.; Morton, D.
Chem. Soc. Rev. 2011, 40, 1857. (f) Zhang, Z.; Wang, J. Tetrahedron
2008, 64, 6577.
1
light yellow liquid (99 mg, 82%); H NMR (600 MHz, CDCl3) δ
7.31−7.28 (m, 4H), 7.24 (t, J = 8.4 Hz, 1H), 4.91 (s, 1H), 4.48 (dd, J
= 5.9, 8.3 Hz, 1H), 3.52 (s, 3H), 3.19 (s, 3H), 3.15 (dd, J = 8.3, 13.6
Hz, 1H), 3.08 (dd, J = 5.8, 13.6 Hz, 1H), 1.48 (s, 9H); 13C NMR (150
MHz, CDCl3) δ 171.6, 166.7, 141.3, 128.2, 127.5, 126.7, 93.8, 81.9,
79.2, 56.8, 55.3, 40.3, 28.3; HRMS calcd for C17H24O4 292.1675, found
292.1668.
(2) For selected examples for carbocyclic cycloadducts, see:
(a) Deng, L.; Giessert, A. J.; Gerlitz, O. O.; Dai, X.; Diver, S. T.;
Davies, H. M. L. J. Am. Chem. Soc. 2005, 127, 1342. (b) Davies, H. M.
L. Adv. Cycloaddition 1999, 5, 119. (c) Davies, H. M. L.; Xing, B.;
Kong, N.; Stafford, D. G. J. Am. Chem. Soc. 2001, 123, 7461.
(d) Davies, H. M. L.; Clark, T. J.; Smith, H. D. J. Org. Chem. 1991, 56,
3819. (e) Liu, Y.; Bakshi, K.; Zavalij, P.; Doyle, M. P. Org. Lett. 2010,
12, 4304. (f) Olson, J. P.; Davies, H. M. L. Org. Lett. 2008, 10, 573.
(3) For oxacyclic cycloadducts, see: (a) Xu, X.; Hu, W.-H.; Zavalij, P.
Y.; Doyle, M. P. Angew. Chem., Int. Ed. 2011, 50, 11152. (b) Doyle, M.
P.; Hu, W.; Timmons, D. J. Org. Lett. 2001, 3, 3741.
(4) For azacyclic cycloadducts, see selected reviews: (a) Doyle, M. P.;
Yan, M.; Hu, W.; Gronenberg, L. J. Am. Chem. Soc. 2003, 125, 4692.
́
(b) Barluenga, J.; Lonzi, G.; Riesgo, L.; Lopez, L. A.; Tomas, M. J. Am.
Chem. Soc. 2010, 132, 13200. (c) Yang, M.; Jacobsen, N.; Hu, W.;
Gronenberg, L. S.; Doyle, M. P.; Colyer, J. T.; Bykowski, D. Angew.
Chem., Int. Ed. 2004, 43, 6713. (d) Wang, X.; Xu, X.; Zavalij, P.; Doyle,
M. P. J. Am. Chem. Soc. 2011, 133, 16402. (e) Lian, Y.; Davies, H. M.
L. J. Am. Chem. Soc. 2010, 132, 440. (f) Xu, X.; Ratnikov, M. O.;
Zavalij, P. Y.; Doyle, M. P. Org. Lett. 2011, 13, 6122.
(E)-Allyl 3,5-dimethoxy-5-phenylpent-2-enoate (8c): light
yellow liquid (96 mg, 76%); H NMR (600 MHz, CDCl3) δ 7.32−
1
7.28 (m, 4H), 7.23 (d, J = 7.4 Hz, 1H), 5.95−5.89 (m, 1H), 5.29 (dd, J
= 1.5, 17.2 Hz, 1H), 5.20 (dd, J = 1.3, 10.4 Hz, 1H), 5.04 (s, 1H),
4.57−4.56 (m, 2H), 4.50 (dd, J = 5.2, 8.7 Hz, 1H), 3.56 (s, 3H), 3.20−
3.14 (m, 4H), 3.08 (dd, J = 5.2, 13.6 Hz, 1H); 13C NMR (150 MHz,
CDCl3) δ 173.5, 166.9, 141.3, 132.8, 128.2, 127.6, 126.6, 117.7, 91.6,
81.9, 64.3, 56.9, 55.6, 40.9; HRMS calcd for C16H20O4 276.1362, found
276.1364.
(E)-Benzyl 3,5-dimethoxy-5-phenylpent-2-enoate (8d): light
1
yellow liquid (82 mg, 74%); H NMR (600 MHz, CDCl3) δ 7.34−
7.28 (m, 10H), 5.19−5.08 (m, 2H), 5.07 (s, 1H), 4.51 (dd, J = 5.2, 8.7
Hz, 1H), 3.56 (s, 3H), 3.20 (s, 3H), 3.18−3.06 (m, 2H); 13C NMR
(150 MHz, CDCl3) δ 173.6, 167.2, 141.3, 136.6, 128.6 128.5, 128.4,
128.3, 128.2, 128.1, 91.7, 81.9, 65.4, 56.9, 55.6, 40.9; HRMS calcd for
C20H22O4 326.1518, found 326.1512.
(E)-6,8-Dimethoxy-8-phenyloct-5-en-4-one (8e): light yellow
1
liquid (95 mg, 72%); H NMR (600 MHz, CDCl3) δ 7.34 (d, J = 7.3
Hz, 2H), 7.31 (t, J = 7.8 Hz, 2H), 7.22 (d, J = 7.3 Hz, 1H), 5.43 (s,
1H), 4.51 (dd, J = 5.1, 8.8 Hz, 1H), 3.58 (s, 3H), 3.18 (s, 3H), 3.13
(dd, J = 5.1, 13.3 Hz, 1H), 3.03 (dd, J = 8.8, 13.3 Hz, 1H), 2.37−2.34
(m, 2H), 1.62−1.57 (m, 2H), 0.90 (t, J = 7.3 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 199.2, 172.7, 141.5, 128.2, 127.5, 126.6, 99.5, 81.9,
56.9, 55.4, 46.7, 41.6, 18.3, 13.8; HRMS calcd for C16H22O3 262.1569,
found 262.1576.
(5) (a) Doyle, M. P.; Kundu, K.; Russel, A. E. Org. Lett. 2005, 7,
5171−5174. (b) Liu, Y.; Zhang, Y.; Jee, N.; Doyle, M. P. Org. Lett.
2008, 10, 1605−1608.
(6) Jadhav, A. M.; Pagar, V. V.; Liu, R.-S. Angew. Chem., Int. Ed. 2012,
51, 11809.
(7) Reviews for the Povarov reactions, see: (a) Povarov, L. S. Russ.
Chem. Rev. 1967, 36, 656. (b) Kouznetsov, V. V. Tetrahedron 2009, 65,
(E)-3,5-Dimethoxy-5-phenyl-1-(thiophene-2-yl)pent-2-en-1-
1
one (8f): light yellow liquid (100 mg, 85%); H NMR (500 MHz,
CDCl3) δ 7.54 (d, J = 5.0 Hz, 1H), 7.40 (d, J = 7.5 Hz, 1H), 7.30 (t, J
= 7.5 Hz, 2H), 7.21−7.07 (m, 4H), 6.06 (s, 1H), 4.64 (dd, J = 5.0, 8.5
Hz, 1H), 3.70 (s, 3H), 3.31−3.13 (m, 5H); 13C NMR (125 MHz,
CDCl3) δ 181.9, 174.9, 145.0, 141.4, 134.1, 132.2, 128.2, 128.1, 126.6,
124.2, 96.4, 81.8, 56.9, 55.7, 42.3; HRMS calcd for C17H18O3S
302.0977, found 302.0974.
́
2721. (c) Bello, D.; Ramon, R.; Lavilla, R. Curr. Org. Chem 2010, 14,
332. (d) McCarrick, M. A.; Wu, Y. D.; Houk, K. N. J. Org. Chem. 1993,
58, 3330.
(8) The crystallographic data of unsaturated acid 7a′ was provided in
Supporting Information.
(9) For reviews on the Prins cyclization, see: (a) Adams, D. R.;
Bhatnagar, S. P. Synthesis 1977, 661. (b) Snider, B. B. In The Prins
Reactions and Carbonyl-ene Reactions; Trost, B. M., Fleming, I.,
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7143.
(E)-3,5-Dimethoxy-1,5-diphenylpent-2-en-1-one (8g): light
1
yellow liquid (103 mg, 86%); H NMR (400 MHz, CDCl3) δ 7.95
(d, J = 8.4 Hz, 1H), 7.86 (d, J = 7.8 Hz, 1H), 7.54−7.40 (m, 6H),
7.34−7.30 (m, 2H), 6.18 (s, 1H), 4.67 (dd, J = 7,2, 13.2 Hz, 1H), 3.71
(s, 3H), 3.28−3.12 (m, 5H);13C NMR (100 MHz, CDCl3) δ 190.2,
174.9, 141.5, 128.5, 128.3, 128.2, 127.9, 127.6, 127.5, 127.0, 96.8, 81.9,
56.9, 55.7, 42.2; HRMS calcd for C19H20O3 296.1412, found 296.1410.
(10) For selected examples, see: (a) Jasti, R.; Rychnovsky, S. D. J.
Am. Chem. Soc. 2006, 128, 13640. (b) Lee, C.-H. A.; Loh, T.-P.
E
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Note
Tetrahedron Lett. 2006, 47, 1641−1644. (c) Overman, L. E.;
Veltthuisen, E. J. J. Org. Chem. 2006, 71, 1581−1587. (d) Bolla, M.
L.; Patterson, B.; Rychnovsky, S. D. J. Am. Chem. Soc. 2005, 127,
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(13) Prior to 1,2-hydride shift, a preferable conformation is shown in
state D, in which the front C−H bond is aligned with the rear empty
p-orbital with its small Rs group lying on the same side with metal
(M). After this 1,2-shift, the E- and Z-selectivity of products depends
on metal, as depicted by E′. Dimeric Rh has a restricted rotation
barrier to show the Z-selectivity with a small rotation (60°). In
contrast, gold prefers thermodynamically favored E-configured
products because of its facile rotation with 120°.
(14) (a) Davis, H. M. L.; Hougland, P. W.; Cantrell, W. R., Jr. Synth.
Commun. 1992, 22, 971. (b) Padwa, A.; Kulkarni, Y. S.; Zhang, Z. J. J.
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F
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