Unprecedented Intramolecular [4 + 2]-Cycloaddition between a 1,3-Diene and a Diazo Ester

Article abstract of DOI:10.1021/jacs.5b12877

Diazo compounds that are well-known to undergo [3 + 2]-cycloaddition provide the first examples of the previously unknown [4 + 2]-cycloaddition with dienes that occur thermally under mild conditions and in high yields. Reactions are initiated from reactants prepared from propargyl aryldiazoacetates that undergo gold(I)-catalyzed rearrangement to activated 1,3-dienyl aryldiazoacetates. These reactions proceed to mixtures of both [4 + 2]-cycloaddition and the 1,3-dienyl aryldiazoacetate after long reaction times. At short reaction times, however, both E- and Z-1,3-dienyl aryldiazoacetates are formed and, after isolation, thermal reactions with the E-isomers form the products from [4 + 2]-cycloaddition with δH^?₂₉₈ = 15.6 kcal/mol and δS^?₂₉₈ = -27.3 cal/(mol·°C). The Z-isomer is inert to [4 + 2]-cycloaddition under these conditions. The Hammett relationships from aryl-substituted diazo esters (p = +0.89) and aryl-substituted dienes (p = -1.65) are consistent with the dipolar nature of this transformation.

Full text of DOI:10.1021/jacs.5b12877

Subscriber access provided by NEW MEXICO STATE UNIV
Communication
Unprecedented Intramolecular [4+2]-Cycloaddition
Between a 1,3-Diene and a Diazo Ester
Huang Qiu, Harathi D Srinivas, Peter Y. Zavalij, and Michael P Doyle
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b12877 • Publication Date (Web): 21 Jan 2016
Downloaded from http://pubs.acs.org on January 23, 2016
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.
Journal of the American Chemical Society 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
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Unprecedented Intramolecular [4+2]-Cycloaddition Between a
1,3-Diene and a Diazo Ester
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
Huang Qiu,†, ‡, § Harathi D. Srinivas,† Peter Y. Zavalij,‡ and Michael P. Doyle*,†
†Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas 78249, United States
‡Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States
§Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and
Molecular Engineering, East China Normal University, Shanghai 200062, China
Supporting Information Placeholder
of the diene. To design such a system we were encouraged by a
recent
ABSTRACT: Diazo compounds that are well known to undergo
[3+2]ꢀcycloaddition provide the first examples of the previously
unknown [4+2]ꢀcycloaddition with dienes that occur thermally
under mild conditions and in high yields. Reactions are initiated
Scheme 1. Reactions of Dienes with Diazo Compounds,
Allenes and Ketenes.
from reactants prepared from propargyl aryldiazoacetates that
undergo gold(I)ꢀcatalyzed rearrangement to activated 1,3ꢀdienyl
aryldiazoacetates. These reactions proceed to mixtures of both
[4+2]ꢀcycloaddition and the 1,3ꢀdienyl aryldiazoacetate after long
reaction times. At short reaction times, however, both Eꢀ and Zꢀ
1,3ꢀdienyl aryldiazoacetates are formed and, after isolation, therꢀ
mal reactions with the Eꢀisomers form the products from [4+2]ꢀ
cycloaddition with ꢀ ꢀ
H‡298 = 15.6 kcal/mol and S‡298 = ꢀ27.3 cal/
(mol•℃). The Zꢀisomer is inert to [4+2]ꢀcycloaddition under these
conditions. The Hammett relationships from arylꢀsubstituted diazo
esters (ρ = +0.89) and arylꢀsubstituted dienes (ρ = ꢀ1.65) are conꢀ
sistent with the dipolar nature of this transformation.
report by M. Brewer and coworkers of a polar intramolecular
[4+2]ꢀcycloaddition of arylꢀ1ꢀazaꢀ2ꢀazoniaallene salts that proꢀ
duced protonated azomethine imines.10 One such structural design
appropriate for intramolecular [4+2]ꢀcycloaddition between a
diene and a diazocarbonyl compound (Scheme 2) would produce
a dipolar azomethine species (2) that could serve as a suitable
stabilized product. Add to this design activation of the diene with
electronꢀdonating substituents, as well as further stabilization of
the dipolar azomethine product, and this cycloaddition reaction
appears feasible. However, additional constraints that include the
linkage between the diene and the diazo units, as well as the geꢀ
ometry of attachment to the diene, remain unresolved.
In the long history of DielsꢀAlder reactions there has not been a
reported example of [4+2]ꢀcycloaddition between a diene and a
diazo compound.1 Their isoelectronic allene and ketene counterꢀ
parts, however, do undergo these reactions and have received
considerable attention. Concerted thermal [4+2]ꢀcycloaddition
reactions of dienes with highly polarized allenes have been extenꢀ
sively investigated,2 but favorable competing stepwise [2+2]ꢀ
cycloaddition reactions diminish their synthetic importance. Tranꢀ
sitionꢀmetalꢀcatalyzed alleneꢀdiene cycloaddition reactions, altꢀ
hough recent in their discovery,3 have circumvented this competiꢀ
tion and become a mainstay of new process developments.4 Keꢀ
tenes readily undergo [2+2]ꢀcycloaddition5 and, recently, [4+2]ꢀ
cycloaddition reactions, but for the latter only with highly activatꢀ
ed diene equivalents6 or with the aid of suitable catalysts7. In conꢀ
trast, diazo compounds commonly react with one double bond of
dienes by dipolar cycloaddition8 or, following dinitrogen extruꢀ
sion, by cyclopropanation9 (Scheme 1), but not by [4+2]ꢀ
cycloaddition.
Scheme 2. Proposed Intramolecular [4+2]-Cycloaddition of
Dienes with Diazo Compounds.
That [4+2]ꢀcycloaddition reactions occur with allenes and keꢀ
tenes, but not with diazo compounds suggested to us that the facilꢀ
ity with which diazo compounds undergo dipolar cycloaddition
prevent [4+2]ꢀcycloaddition and that, if dipolar cycloaddition
could be electronically and/or sterically inhibited, perhaps [4+2]ꢀ
cycloaddition should be observed. Inhibition of dipolar cycloaddiꢀ
tion with deactivation of the carbonꢀcarbon double bond towards
dipolar cycloaddition would require constraints in the alignment
of the diazo functional group with either one of the double bonds
For this investigation we chose to synthesize dieneꢀlinked arꢀ
yldiazoacetates 1 (Scheme 3). This structure contains the elements
of activation and stabilization that we believe to be requirements
for dieneꢀdiazo [4+2]ꢀcyclization.11 Goldꢀcatalyzed 1,3ꢀacyloxy
migration of propargylic carboxylates is known to form allene
intermediates (3) suitable for diene formation, and the generation
of dienes from propargylic esters through a gold(I)ꢀcatalyzed 1,3ꢀ
migratory cascade involving allene intermediates has been estabꢀ
lished.12
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 6
temperature or solvent, suggested that the two products were
formed from a common intermediate, which in the case of the
1
apparent cyloaddition product 2 could be (E)ꢀ1.
2
3
Scheme 3. Synthesis of Diene-linked Aryldiazoacet-ates.
To determine if both (E)ꢀ1 and (Z)ꢀ1 were formed initially after
which (E)ꢀ1 underwent cycloaddition to 2 we examined the gold
catalyzed reaction at shorter reaction times. If (E)ꢀ1 was the preꢀ
cursor to 2, this diene should be observed as an initially formed
product. Fortunately, during 6ꢀ12 h reaction time at room temperꢀ
ature with relatively low conversion of 4, both (E)-1 and (Z)-1
were obtained at apparent equivalent rates. Isolation of (E)-1a by
column chromatography at room temperature provided sufficient
material to examine if this diene could undergo uncatalyzed forꢀ
mation of 2a or if cycloaddition required the intervention of a
catalyst. In the absence of catalyst, isolated (E)ꢀ1a underwent
quantitative conversion to cycloaddition product 2a in toluene at
room temperature for 4 days. Furthermore, compound (E)-1a was
dissolved in CDCl3 and the progress of the reaction was monitored
by 1H NMR spectroscopy. Reaction was first order in (E)ꢀ1a with
kobs = 9.6×10ꢀ5 sꢀ1 at 41℃ in CDCl3 (Figure 2); and the addition of
the gold catalyst in amounts similar to those used for reactions
with propargyl aryldiazoacetates 4 did not influence the rate of
conversion of (E)-1a to 2a, confirming that the cycloaddition
reaction was uncatalyzed. The variation of rate constant over temꢀ
peratures ranging from 20℃ to 49℃ provided Eact = 16.2 kcal/mol,
ꢀH‡298 = 15.6 kcal/mol and ꢀS‡298 = ꢀ27.3 cal/ (mol•℃). Multiple
determinations of reaction rates after separations of (E)-1a from
different reaction mixtures were made to ensure that there was
consistency in results. Cycloaddition occurred with rate constants
that were independent of the batch source of (E)ꢀ1a.
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
Treatment of propargyl phenyldiazoacetates 4 with a broad seꢀ
lection of neutral gold catalysts under various conditions of temꢀ
peratures and solvents gave either no reaction or complex product
mixtures (see SI, Table S1) that suggested the formation of diene
1, although not in high yield. Sensing that proton transfer might
be limiting this process, a variety of bases were used as additives
but without improvement in the yield of 1 (see SI, Table S2).
However, reactions using a pyridineꢀNꢀoxide in stoichiometric
amounts resulted in the formation of (Z)ꢀ1 and a product anticiꢀ
pated from dieneꢀdiazo [4+2]ꢀcycloaddition (2) in a combined
yield of up to 74% (eq 1). Uses of pyridineꢀNꢀoxides as bases
rather than oxygen transfer agents have been reported.13
AuCl(Me2S) and 4ꢀchloropyridineꢀNꢀoxide were optimal for the
reaction performed in toluene at 20℃ (see SI, Table S3). Strucꢀ
tures for both the diene (Z)ꢀ1e and cycloaddition product 2f were
confirmed by Xꢀray diffraction (Figure 1). Both the cascade reacꢀ
tion anticipated from initial dinitrogen extrusion by the catalyst at
the diazo carbon14 and product(s) from dipolar cycloaddition beꢀ
tween the diazo compound and diene were not observed, and the
absence of the cascade reaction product indicated a high preferꢀ
ence of the gold catalyst for reaction at the carbonꢀcarbon triple
bond rather than with the phenyldiazoacetate. Homologous prodꢀ
ucts were formed using the cyclohexyl analogue of 4a, but not
with the dimethyl analogue, and replacing the phenyl group of the
alkyne with TMS prevented goldꢀcatalyzed reaction presumably
due to steric restrictions.
Reaction time/sec
0.2
0
0
2000
4000
6000
8000
10000
12000
-0.2
-0.4
-0.6
-0.8
-1
N2
H
y = -0.000096x + 0.003189
R² = 0.9996
O
N
H
N
O
O
-1.2
Br
O
Cl
1e
(Z)-
2f
Figure 1. Xꢀray structures of diene (Z)ꢀ1e and cycloaddition
product 2f. CCDC 1422281 contains supplementary crystalloꢀ
graphic data for (Z)ꢀ1e, and CCDC 1423163 contains supplemenꢀ
tary crystallographic data for 2f.
Figure 2. Linear relationship between reaction time and ln [(E)ꢀ
1a/ (E)ꢀ1a0]. Reaction performed in CDCl3 at 41℃.
Surprisingly, the geometrical isomer of (Z)-1a did not undergo
[4+2]ꢀcycloaddition. Stable at room temperature in the absence of
catalyst for more than 7 days in toluene, (Z)-1a underwent comꢀ
plete decomposition resulting in complex mixtures at 60℃ in
CDCl3 for 24 h that did not include evidence for 2a or similar
cycloaddition products. In contrast, (E)ꢀ1a underwent what is a
facile [4+2]ꢀcycloaddition reaction that occurred without evidence
for formation of a dipolar cycloaddition product.
The influence of aryl substituents, including ethers, halides, niꢀ
tro, trifluoromethyl, alkyl, and aryl, of both the diazoacetate and
the propargyl functional groups was examined to further underꢀ
stand the formation of dieneꢀlinked aryldiazoacetates and the
dieneꢀdiazo [4+2]ꢀcycloaddition process (see SI, Table S4). The
variation in the ratio of products (Z)ꢀ1:2 was low (26:74 to 50:50)
despite high levels of conversion (70ꢀ94% yields), although
strongly electronꢀwithdrawing substituents on aryl group visibly
slowed the rate of reaction. That the ratio of products was miniꢀ
mally influenced by substituents and, in separate experiments, by
The design of (E)ꢀ1 with its strategically placed phenyl groups
allows the examination of the influence substituents on the rates
for cycloaddition for both the dienophile and the diene in the same
ACS Paragon Plus Environment

Page 3 of 6
Journal of the American Chemical Society
compound. To perform these determinations we isolated (E)ꢀ1
5
6
7
4
4
2
88f (52)
91f (50)
85f (56)
3.04×10ꢀ5
2.38×10ꢀ5
9.82×10ꢀ5
41:59
40:60
26:74
1
2
3
4
5
6
7
8
from a representative series of goldꢀcatalyzed reactions of 4, deꢀ
termined the yields for their conversion to [4+2]ꢀcycloaddition
product, and measured the rates for their conversion to 2 at conꢀ
stant temperature. As shown in Table 1, the intramolecular [4+2]ꢀ
cycloaddition reaction of (E)ꢀ1 gave 2 in high yields with comꢀ
plete diastereocontrol. Reaction rates were dependent on the comꢀ
pounds (E)ꢀ1 with arylacetic acidꢀderived substituents Ar1 and
arylacetyleneꢀderived aryl substituents Ar2. pꢀTolylacetic acidꢀ
derived substituent slightly decreased the reaction rate (Table 1,
entry 2); other arylacetic acidꢀderived substituents, such as pꢀPh,
pꢀBr, pꢀCl, and pꢀF, increased the reaction rate (Table 1, entries 3ꢀ
6); moreover, the aryldiazoacetate with the strongly electronꢀ
withdrawing pꢀNO2 group gave the highest reaction rate (Table 1,
entry 7). In contract, electronꢀwithdrawing group on benzene ring
of the phenylacetyleneꢀderived substituents decreased the reaction
rate (Table 1, entries 11ꢀ14), whereas electronꢀdonating groups
increased the reaction rate (Table 1, entries 9 and 10). Hammett
plots of the intermolecular [4+2]ꢀcycloaddition reaction of (E)ꢀ1
showed good correlations between σ values and log (kX/kH) with
ρꢀvalues of +0.89 (R2 = 0.96) for the paraꢀsubstituted aryldiazo
esters and ꢀ1.65 (R2 = 0.95) for the paraꢀsubstituted aryldienes
(See SI, Figures 6 and 7). The diazo functional group exhibits
electrophilic character in these reactions while the diene is its
nucleophilic partner. In addition, the oꢀbromophenylacetic acidꢀ
derived substituent underwent reaction much slower than did the
p-bromophenylacetic acidꢀderived compound, suggesting a possiꢀ
ble steric inhibition (Table 1, entry 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
8
21
4
87 (55)
92f (42)
90 f (45)
88f (45)
88f (45)
89 (45)
87 (41)
0.33×10ꢀ5
3.71×10ꢀ5
3.04×10ꢀ5
0.72×10ꢀ5
0.86×10ꢀ5
0.45×10ꢀ5
0.30×10ꢀ5
27:73
50:50
48:52
47:53
45:55
45:55
47:53
9
10
11
12
13
14
4
7
Table 1. Product and Kinetic Studies of Intramolecular
[4+2]-Cycloaddition.
7
15
21
Entrya
2
timeb
yield of
2 from
(E)-1c
(directly
from 4)
rate conꢀ
stantd
(sꢀ1)
(Z)-
1:2e
(days)
1
4
4
90f (48)
1.50×10ꢀ5
40:60
42:58
aReactions were performed at 20 ± 0.5℃ on a 0.05 mmol scale:
under a nitrogen atmosphere. The solution of (E)ꢀ1 in 0.5 mL
CDCl3 was monitored by 1H NMR spectroscopy every a period of
time until over 80% of (E)ꢀ1 was converted into the cycloaddition
product 2. bThe reaction time was determined from the disappearꢀ
2
92f (54)
1.47×10ꢀ5
ance of (E)ꢀ1 by 1H NMR spectroscopy. Isolated yields from the
c
d
1
e
conversions of (E)-1 to 2. Determined by H NMR. Ratio of
isolated products from AuCl(Me2S) catalyzed reaction of 1; the
yields of 1+2 ranged from 70 to 94% with the average yield being
84%. The solution of (E)-1 and (Z)-1 in 0.5 mL CDCl3 was
monitored by H NMR spectroscopy; conversion of (E)-1 to 2
3
4
4
4
93f (53)
90f (50)
2.57×10ꢀ5
3.41×10ꢀ5
42:58
44:56
f
1
occurred without any noticeable conversion of (Z)-1.
The reactivity of diazo compounds towards gold catalysts is of
increasing interest,15 but there are few indicators of their relative
preference in molecular systems that contain both diazo and alꢀ
kyne functional groups. Clearly the preference is for the alkyne
functional group in reactions with 4 with the aryldiazoacetate inert
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 6
towards the gold catalyst. Indeed, when 4 is treated with
thanks the China Scholarship Council for a fellowship. We thank
1
2
3
4
5
6
7
8
AuCl(Me2S) in the presence of methyl phenyldiazoacetate, the
added phenyldiazoacetate had no effect on the rate of reaction, on
the yield of products, or on the 2:(Z)ꢀ1 ratio. However, use of
ethyl diazoacetate in place of methyl phenyldiazoacetate caused
virtually instantaneous reduction of the gold catalyst to metallic
gold without causing any reaction with 4.
Hadi Arman for crystallographic data and analysis. The HRMS
used in this research was supported by a grant from the National
Institutes of Health (G12MD007591).
REFERENCES
(1) For selected reviews, see: (a) Hammer, J. 1,4-Cycloaddition Reac-
tion: The Diels-Alder Reaction in Heterocyclic Syntheses; Elsevier, New
York, 2013. (b) Carruthers, W. Cycloaddition Reactions in Organic Syn-
thesis; Elsevier, New York, 2013. (c) Nicolaou, K. C.; Snyder, S. A.;
Montagnon, T.; Vassilikogiannakis, G. Angew. Chem. Int. Ed. 2002, 41,
1668. (d) Masson, G. Chem. Soc. Rev. 2013, 42, 902.
(2) (a) Pham, H. V.; Houk, K. N. J. Org. Chem. 2014, 79, 8968. (b)
Ma, S. Chem. Rev. 2005, 105, 2829. (c) Murakami, M.; Itami, K.; Ito, Y.
J. Am. Chem. Soc. 1997, 119, 7163.
(3) Wender, P. A.; Jenkins, T. E.; Suzuki, S. J. Am. Chem. Soc. 1995,
117, 1843.
(4) (a) González, A. Z.; Toste, F. D. Org. Lett. 2010, 12, 200. (b)
Mauleón, P.; Zeldin, R. M.; González, A.Z.; Toste, F. D. J. Am. Chem.
Soc. 2009, 131, 6348. (c) López, F.; Mascareñas, J. L. Beilstein J. Org.
Chem. 2013, 9, 2250.
(5) Allen, A. D.; Tidwell, T. T. Chem. Rev. 2013, 113, 7287.
(6) (a) Tidwell, T. T. Ketenes; Wiley, New York, 1995. (b) Brady, W.
T.; Agho, M. O. J. Org. Chem. 1983, 48, 5337.
(7) (a) Bekele, T.; Shah, M. H.; Wolfer, J.; Abraham, C. J.; Weathꢀ
ewax, A.; Lectka, T. J. Am. Chem. Soc. 2006, 128, 1810. (b) Abrham,C.
J.; Paull, D. H.; Scerba, M. T.; Grebinski, J. W.; Lectka, T. J. Am. Chem.
Soc. 2006, 128, 13370. (c) Huang, X.; He, L.; Shao, P.; Ye, S. Angew.
Chem. Int. Ed. 2009, 48, 192. (d) Jian, T.; Shao, P.; Ye, S. Chem. Com-
mun. 2011, 47, 2381.
(8) a) Saga, H.; Itoh, K. In Methods and Applications of Cycloaddition
Reactions in Organic Syntheses; Wiley, New York, 2014. (b) Jiang, N.;
Li, C. Chem. Commun. 2004, 40, 394.
(9) Doyle, M. P.; McKervey,M. A.; Ye, T. Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds; John Wiley & Sons Inc.,
New York, 1998.
The [4+2]ꢀcycloaddition products formed from (E)ꢀ1 are stable
dipolar species, and their suitability towards dipolar cycloaddition
with reactive alkenes and alkynes was examined. Treatment of 2e
with Nꢀphenylmaleimide at room temperature for 6 h gave the
nitrogenꢀfused pentacyclic compound 5e in 85% yield with comꢀ
plete diastereocontrol (eq 2). The structure of 5e was confirmed
by Xꢀray diffraction.16
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
In summary, arylꢀsubstituted 1ꢀ(1,3ꢀdienyl) aryldiazoacetates
were formed selectively and in moderate to high yields by Au(I)ꢀ
catalyzed rearrangement of propargyl phenyldiazoacetates perꢀ
formed in the presence of a pyridineꢀNꢀoxide. Complete selectiviꢀ
ty for Au(I) activation of the alkyne rather than metallocarbene
formation from the diazoacetate occurred, and both arylꢀ
substituted 1ꢀ(1,3ꢀdienyl) aryldiazoacetates and the products from
intramolecular [4+2]ꢀcycloaddition of the diazo N=N bond to the
diene were formed. Arylꢀsubstituted (E)ꢀ1ꢀ(1,3ꢀdienyl) aryldiazoꢀ
acetates underwent intramolecular [4+2]ꢀdieneꢀdiazo cycloaddiꢀ
tion under mild conditions without catalysis by the Au(I) reagent
used in its formation and without evidence of a competing dipolar
cycloaddition. Cycloaddition was first order in the substrate, and
both the activation parameters and the Hammett relationships for
the conversion of (E)ꢀ1 to 2 are consistent with those for other
intramolecular DielsꢀAlder reactions.17
(10) Bercovici, D. A.; Ogilvie,J. M.; Tsvetkov,N.; Brewer, M. Angew.
Chem. Int. Ed. 2013, 52, 13338.
(11) (a) Zhang, L. in Contemporary Carbene Chemistry, Moss, R. A.;
Doyle, M. P., Eds., pages 526–551, Wiley, New York, 2014. (b) Wang,
Y.; Lackner, A. D.; Toste, F. D. Acc. Chem. Res. 2014, 47, 889.
(12) (a) Shiroodi, R. K.; Dudnik, A. S.; Gevorgyan, V. J. Am. Chem.
Soc. 2012, 134, 6928. (b) Shiroodi, R. K.; Gevorgyan, V. Chem. Soc. Rev.
2013, 42, 4991. (c) Fensterbank, L.; Malacria, M. Acc. Chem. Res. 2014,
47, 953. (d) Briones, J. F.; Davies, H. M. L. J. Am. Chem. Soc., 2012, 134,
11916. (e) Yu, Z.; Ma, B.; Chen, M.; Wu, H.ꢀH.; Liu, L.; Zhang, J. J. Am.
Chem. Soc., 2014, 136, 6904.
(13) (a) Ye, L.; Wang, Y.; Aue, D.; Zhang L J. Am. Chem. Soc. 2012,
134, 31. (b) Wang, Y.; Yepremyan, A.; Ghorai, S.; Todd, R.; Aue, D.;
Zhang L. Angew. Chem. Int. Ed. 2013, 52, 7795. (c) Zhou, L.; Zhang, M.;
Li, W.; Zhang, J. Angew. Chem. Int. Ed. 2014, 53, 6542.
(14) (a) Burgess, K.; Lim, H.; Porte, A. M.; Sulikowski G. A. Angew.
Chem. Int. Ed. 1996, 35, 220. (b) Briones J. F.; Davies H. M. L. J. Am.
Chem. Soc. 2012, 134, 11916. (c) Yu, Z.; Ma,B.; Chen, M.; Wu, H.ꢀH.;
Liu, L.; Zhang, J. J. Am. Chem. Soc. 2014, 136, 6904. (c) Zhang, D.; Xu,
G.; Ding, D.; Zhu, C.; Li J.; Sun, J. Angew. Chem. Int. Ed. 2014, 53,
11070. (e) Zhou, L.; Liu, Y.; Zhang, Y.; Wang, J. Beilstein J Org Chem.
2011, 7, 631.
(15) Wei, F.; Song, C.; Ma, Y.; Zhou, L.; Tung, C.; Xu, Z. Science Bul-
letin, 2015, 60, 1479.
(16) CCDC 1438960 contains supplementary crystallographic data for
5e.
(17) (a) Liu, F.; Paton, R. S.; Kim, S.; Liang, Y.; Houk, K. N. J. Am.
Chem. Soc. 2013, 135, 15642. (b) Limanto, J.; Khuong,K. S.; Houk, K. N.;
Snapper, M. L. J. Am. Chem. Soc. 2003, 125, 16310. (c) Tantillo,D. J.;
Houk, K. N.; Jung M. E. J. Org. Chem. 2001, 66, 1938.(d) Jung, M. E.;
Gervay, J. J. Am. Chem. Soc. 1991, 113, 224.
ASSOCIATED CONTENT
Supporting Information
Experimental procedures and full characterization of propargyl
phenyldiazoacetates and their diene and [4+2]ꢀcycloaddition
products, Xꢀray and spectral determinations, and kinetic analyses.
This material is available free of charge via the Internet at
http://pubs.acs.org. .
AUTHOR INFORMATION
Corresponding Author
michael.doyle@utsa.edu
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
Support for this research from the National Science Foundation
(CHEꢀ1212446) and UTSA is gratefully acknowledged. HQ
ACS Paragon Plus Environment

Page 5 of 6
Journal of the American Chemical Society
TOC:
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
5
ACS Paragon Plus Environment

Journal of the American Chemical Society
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
225x80mm (300 x 300 DPI)
ACS Paragon Plus Environment