Divergent C-H Insertion-Cyclization Cascades of N-Allyl Ynamides

Article abstract of DOI:10.1002/anie.201507167

Gold carbene reactivity patterns were accessed by ynamide insertion into a C(sp³)-H bond. A substantial increase in molecular complexity occurred through the cascade polycyclization of N-allyl ynamides to form fused nitrogen-heterocycle scaffol

Full text of DOI:10.1002/anie.201507167

Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201507167
German Edition: DOI: 10.1002/ange.201507167
Cyclization Reactions
À
Divergent C H Insertion–Cyclization Cascades of N-Allyl Ynamides
Holly V. Adcock, Elli Chatzopoulou, and Paul W. Davies*
Abstract: Gold carbene reactivity patterns were accessed by
3
À
ynamide insertion into a C(sp ) H bond. A substantial
increase in molecular complexity occurred through the cascade
polycyclization of N-allyl ynamides to form fused nitrogen-
heterocycle scaffolds. Exquisite selectivity was observed despite
several competing pathways in an efficient gold-catalyzed
synthesis of densely functionalized C(sp3)-rich polycycles and
a copper-catalyzed synthesis of fused pyridine derivatives. The
respective gold–keteniminium and ketenimine activation path-
ways have been explored through a structure–reactivity study,
À
and isotopic labeling identified turnover-limiting C H bond-
cleavage in both processes.
A
ccess to molecules with stereogenic centers and a higher
fraction of C(sp3) is increasingly desirable in pharmaceutical
fragment design and lead discovery, as it is associated with
improving chances of clinical success.[1] The use of p-acid
catalysis to generate metal–carbene character directly from
triple bonds offers a rapid route to molecular complexity.[2]
Ynamides are attracting increasing attention in this regard, as
the polarized p-system allows for regioselective carbenoid
formation in the presence of other p-systems, oxidants, or
nitrenoids.[3–5] Potent transformations based on this approach
enable the elaboration of a C(sp) C(sp) unit into C(sp )
C(sp ) or C(sp ) C(sp ) units. We envisioned that the
challenging C(sp ) C(sp ) system might be directly accessed
from ynamides if a carbenoid could be generated by s-bond
insertion and then quenched by cyclization onto the nitrogen
substituent (Scheme 1a).
2
À
À
2
3
2
À
3
3
À
Scheme 1. Generation of gold carbenes from ynamides by carbocycliza-
tion. PG=protecting group.
With reference to this strategy, a gold carbene was formed
À
previously by the formal insertion of an ynamide into a C O
bonds, three new fused rings, and up to four contiguous
stereocenters.
s-bond (Scheme 1b).[6,7] However, further cyclization was not
observed. Instead, 1,2-migration dominated to give indenyl
amides, regardless of the substituents present. Herein we
show that carbenoid-based polycyclization can be induced by
An ynamide polycyclization cascade was pursued by the
use of an N-allyl substituent as a viable carbenoid-quenching
unit.[5h,i,n,11] Although several AuI species/solvent combina-
tions afforded only indenyl amides 2a/b at room temperature,
a breakthrough occurred when 1a was heated with [Au(pi-
colinate)Cl2][12] in toluene (Table 1, entries 1 and 2; see also
the Supporting Information). New diastereomeric products
3
[8–10]
À
the C(sp ) H insertion of ynamides (Scheme 1c).
Nota-
bly, exquisite selectivity was established over several diver-
gent pathways in the preparation of heteroaromatic com-
pounds or N-heterocycles with three new C(sp ) C(sp )
3
3
À
À
3a arose from insertion into the benzylic C H s-bond rather
À
than the C O s-bond. The relative configuration across the
fused ring junction is fixed. The methoxy group in 3a is anti to
the cyclopropyl methylene unit in the major diastereomer
(see the Supporting Information).[13] The product distribution
depended on the temperature, solvent, and catalyst.[14]
Indenes 2a/b were favored at lower temperatures and in
more polar solvents (Table 1, entries 3–6; see also the
Supporting Information). At higher temperatures, the use of
AuCl3 or AuBr3 gave 3a in lower yield and a 1,4-disubstituted
isoquinoline 4 (Table 1, entries 7–10; see also the Supporting
Information), which was also the main product with AuI
species. Degradation of 1a was seen with BF3·OEt2, whereas
[*] Dr. H. V. Adcock, E. Chatzopoulou, Dr. P. W. Davies
School of Chemistry
University of Birmingham, Birmingham (UK)
E-mail: p.w.davies@bham.ac.uk
Supporting information and ORCID(s) from the author(s) for this
article are available on the WWW under http://dx.doi.org/10.1002/
anie.201507167.
ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co.
KGaA. This is an open access article under the terms of the Creative
Commons Attribution License, which permits use, distribution and
reproduction in any medium, provided the original work is properly
cited.
Angew. Chem. Int. Ed. 2015, 54, 15525 –15529
ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
15525

.
Angewandte
Communications
Table 1: Effect of reaction conditions on product distribution.[a]
Electron-donating and electron-
withdrawing groups were well tol-
erated (products 3k and 3m–o),
and a larger-scale reaction of 1o
proceeded smoothly with a reduced
catalyst loading. In contrast, sub-
strates 1l,p with large groups flank-
ing the ynamide did not undergo the
desired transformation. The less
Entry
Catalyst
Solvent
T [8C]
Yield [%][b]
1a/2a/2b/3a(d.r.)/4
1[6]
2
3
4
5
6
7
8
9
10
11
12
13
[(p-CF3C6H4)3PAuCl]/AgNTf2
[Au(picolinate)Cl2]
[Au(picolinate)Cl2]
[Au(picolinate)Cl2]
[Au(picolinate)Cl2]
[Au(picolinate)Cl2]
AuBr3
CH2Cl2
RT
80
RT
–:74 :9 :–:–
–:21:7:61(3.4:1):–
–:54 :32 :9 :–
rigid
dihydronaphthalene-substi-
toluene
toluene
MeNO2
toluene
p-xylene
p-xylene
p-xylene
p-xylene
p-xylene
toluene
p-xylene
toluene
tuted ynamide 1q reacted only
slowly with the AuIII catalyst to
give 3q, which was obtained in
substantially improved yield with
80
–:45 :19 :9 :–
100
120
120
120
120[d]
120[d]
80
–:11:6 :66(2.9:1):–
–:7:5 :75(2.3:1)[c] :–
–:8 :4 :48(2.4:1): <5
–:7:3 :32(1.7:1):22
–:–:–:–:41
a
linear AuICl equivalent. This
result is consistent with gold atom
needing to be in plane with the
hydrocarbon skeleton linking to the
hydride-donor site.
AuCl3
[Ph3PAuCl]/AgNTf2
[(JohnPhos)Au(NCMe)]·SbF6
BF3·OEt2
none
CuI
–:–:–: <5 :27
–:–:–:–:–
120[e]
100[f]
23 :–:–:–:16
The non-aromatic C(sp3)-rich
–:–:–:–:68[g]
polycycles
3r–x
incorporating
[a] General reaction conditions: 1a (0.1 mmol, 1.0 equiv), catalyst (5 mol%), solvent (0.1m); the
reaction mixture was stirred for 6 h unless otherwise stated. [b] Yields were determined by H NMR
spectroscopy. The diastereomeric ratio of 3a is given in parenthesis. [c] The major diastereomer is
shown (isolated in 49% yield). [d] Reaction time: 3 h. [e] Reaction time: 24 h. [f] Reaction time: 8 h.
[g] Product 4 was isolated in 65% yield. Ms=methanesulfonyl, JohnPhos=2-(di-tert-butylphospha-
nyl)biphenyl, Tf =trifluoromethanesulfonyl.
cycloalkyl, piperidine, and pyran
motifs were assembled readily. The
gold-catalyzed reactions proceeded
smoothly, though products 3s–
u from benzylic ethers required
careful handling and purification
on deactivated silica. As illustrated
with 3t, although the catalysis is
1
4 was formed in low yield on heating without an added
catalyst (Table 1, entries 11 and 12). The use of CuI in toluene
at 1008C provided an effective balance between conversion
into 4 and degradation (Table 1, entry 13; see also the
Supporting Information).
Having established reagent control of the competing
pathways for the cyclization of 1a, we undertook a structure–
reactivity investigation. Intriguingly, the N-p-toluenesulfonyl
ynamide 1b underwent faster and cleaner polycyclization to
give 3b in excellent yield with no carboalkoxylation, even at
room temperature (Scheme 2). Preorganization of the sub-
stituents may prevent adoption of the reactive geometry for
carboalkoxylation.[6] Further studies with N-Ts ynamides
sufficiently mild to afford the product in high yield after
20 min at 558C, the polycyclization product undergoes
elimination (to diene 5 in the case of 3t) on further heating
or on exposure to silica (yields and diastereomeric ratios
determined by NMR spectroscopy and after purification by
column chromatography on silica gel are shown in Scheme 2
for two different reaction temperatures.
Further mechanistic insight into the polycyclization was
then sought. Complete deuterium transfer from the benzylic
site to the bridgehead position adjacent to the nitrogen atom
was observed with [D]1 f (Scheme 3). The quantitative
analysis of initial reaction rates was hampered by an induction
period (see the Supporting Information for an NMR
study);[12] however, an approximately fivefold increase in
reaction time was required over that for 1 f.[16,17] N-Homoallyl
ynamide 6 was converted into the piperidine-fused polycycle
7 as the major product. Only a small amount of amidodiene 8
from ene–ynamide cycloisomerization was observed, thus
À
showed that the C H donor site could incorporate an allyloxy
group (product 3c) and an electron-deficient aryl substituent
(product 3d). The electron-rich aryl substituent in 1e was not
tolerated.[15]
Polycycles bearing a protected ketone could be accessed
as single diastereomers by incorporating a dioxolane unit in
the alkyne starting material instead of the benzhydric moiety.
Dimethylacetal and dioxane groups degraded under the
reaction conditions; however, both 1 f and its N-nosylated
analogue 1g reacted smoothly, although 1g required heating.
Substituted dioxolanes were also reactive (products 3h,i). The
formation of 3i as an unequal mixture of diastereomers from
chiral-diol-derived 1i provides promise for a future asym-
metric synthesis of these complex N-heterocycles by a trace-
less-auxiliary approach. Interestingly, diastereoselectivity was
also observed with an a-methyl-N-allyl group; thus, product
3j was obtained with d.r. 4.0:1.
À
showing C H insertion to be kinetically more productive than
the attack of an alkene.[5a,b] N-Benzyl ynamide 9 did not
À
undergo polycyclization, but instead C H insertion occurred
to afford indenyl amide 10.[18] Although further investigation
is needed to explore the full scope of the polycyclization, the
successful reaction with the more rotationally labile homo-
allyl group is promising.
Isoquinoline formation from N-methanesulfonyl yna-
mides 1a/y could be interrupted by adding a base to afford
alkoxy 1,2-dihydroisoquinolines 11a,y, which were readily
converted into 4 (Scheme 4). The conversion of [D]1a took
approximately twice as long as that of 1a and led to full
15526 www.angewandte.org
ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 15525 –15529

Angewandte
Chemie
Scheme 3. Reactions to probe individual steps within the polycycli-
zation cascade.
Scheme 4. Initial exploration of the ynamide cascade cyclization initi-
ated by an aza-Claisen reaction.
À
Scheme 2. Structural effects on the ynamide C H insertion–cyclopro-
aromatization (product 15 f). In stark contrast to the poly-
cyclization, N-Ms ynamides gave faster and cleaner reactions
than N-Ts ynamides (14a vs. 14aa; 4 was formed in 20% yield
from 1b). The rearrangement cascade also tolerated
increased substitution around the ynamide (product 14e)
and electronic variation (products 14c–e). The reactions of
thiophene- and pyridine-derived ynamides highlight the
ability to access other desirable heteroaromatic motifs
(products 14g,h).[19]
panation cascade. Yields are for the isolated product after flash
column chromatography. In each case, the major diastereomer is
shown. [a] o-Xylene (0.1m) was used as the solvent. [b] Product 3h
was isolated as a complex mixture of four diastereomers. [c] The
product was purified on NEt3-deactivated silica. [d] The diastereomeric
ratio before purification was 3.1:1. NR=no reaction, Ns=4-nitro-
benzenesulfonyl, Ts =p-toluenesulfonyl.
deuterium incorporation at the 3-position. The products
derived from dioxolane derivatives 13a–h were generally
isolated as dialkoxy 1,2-dihydroisoquinolines 14 unless elim-
ination was aided by the substitution pattern (product 15d) or
According to our observations and previously reported
studies, the reactions can be rationalized on the basis of
competing activation of the substrate as a gold keteniminium
Angew. Chem. Int. Ed. 2015, 54, 15525 –15529
ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 15527

.
Angewandte
Communications
place of the 1,3-sulfonyl shift shown to be facile with aryl
ynesulfonamides.[24] A 6p electrocyclic ring closure would
give the isolable heterocycles 11/14.[25,26] Neighboring-group-
assisted elimination and desulfonylation would then afford 4/
15. A metal catalyst could potentially play a role during each
stage of this thermally viable cascade.
In summary, the induction of gold carbene character by
3
À
ynamide insertion into a C(sp ) H bond resulted in a novel
polycyclization cascade of N-(homo)allyl ynamides. Superb
selectivity was observed for an array of competing processes
through the appropriate choice of reaction conditions and was
reinforced by structural effects. Two protocols were devel-
oped to access substantial molecular complexity in a single
step with simple catalysts and practically straightforward
reaction conditions: Fused C(sp3)-rich scaffolds resulted from
À
a gold keteniminium pathway, in which C H insertion
outperformed carboalkoxylation and enyne cycloisomeriza-
tion, and heteroaromatic pyridine-fused derivatives were
prepared through ketenimine activation in a copper-catalyzed
rearrangement cascade. Investigations are ongoing to further
elucidate the mechanism, stereocontrol factors, and wider
synthetic potential of these reactions.
Acknowledgements
We thank the EPSRC and AstraZeneca plc (Studentship to
H.V.A.) and the University of Birmingham (Studentship to
E.C.) for funding, Dr. Louise Male (University of Birming-
ham) for X-ray crystallography, and Dr. Thomas Langer
(AstraZeneca plc, Macclesfield, UK) for interesting discus-
sions. Facilities used in this research were in part supported
through Birmingham Science City AM2 by AWM and the
ERDF.
Scheme 5. Proposed mechanistic outline of competing pathways. For
clarity, conformational changes are not shown. ERC=electrocyclic ring
closure.
intermediate A/A’ and ketenimine H (Scheme 5). Deuterium
labeling and the impact of (de)stabilizing substituents (see
products 3k,n,o[20] in Scheme 2) are consistent with the
turnover-limiting formation of benzylic cation B by 1,5-
hydride transfer from A’ (path 1).[21] The gold atom must be
able to align in a plane with the carbon atom of the donor site
(compare 1l–q). Stepwise cyclization, to give gold carbene C,
and cyclopropanation would give 3. An inverted order of
Keywords: carbenes · cyclopropanation · gold ·
nitrogen heterocycles · ynamides
How to cite: Angew. Chem. Int. Ed. 2015, 54, 15525–15529
Angew. Chem. 2015, 127, 15745–15749
À
bond formation, with cyclopropanation occurring before C
[1] a) F. Lovering, Med. Chem. Commun. 2013, 4, 515; b) F.
Lovering, J. Bikker, C. Humblet, J. Med. Chem. 2009, 52, 6752.
[2] For selected reviews, see: a) D. J. Gorin, F. D. Toste, Nature 2007,
446, 395; b) A. Fürstner, P. W. Davies, Angew. Chem. Int. Ed.
2007, 46, 3410; Angew. Chem. 2007, 119, 3478; c) A. S. K.
Hashmi, Chem. Rev. 2007, 107, 3180; d) R. Dorel, A. M.
Echavarren, Chem. Rev. 2015, 115, 9028; e) P. W. Davies, M.
Garzón, Asian J. Org. Chem. 2015, 4, 694.
[3] For reviews on ynamides, see: a) K. A. DeKorver, H. Li, A. G.
Lohse, R. Hayashi, Z. Lu, Y. Zhang, R. P. Hsung, Chem. Rev.
2010, 110, 5064; b) G. Evano, A. Coste, K. Jouvin, Angew. Chem.
Int. Ed. 2010, 49, 2840; Angew. Chem. 2010, 122, 2902; c) X.-N.
Wang, H.-S. Yeom, L.-C. Fang, S. He, Z.-X. Ma, B. L. Kedrowski,
R. P. Hsung, Acc. Chem. Res. 2014, 47, 560.
[4] For the synthesis of ynamides, see: a) Y. S. Zhang, R. P. Hsung,
M. R. Tracey, K. C. M. Kurtz, E. L. Vera, Org. Lett. 2004, 6, 1151;
b) T. Hamada, X. Ye, S. S. Stahl, J. Am. Chem. Soc. 2008, 130,
833; c) A. Coste, G. Karthikeyan, F. Couty, G. Evano, Angew.
Chem. Int. Ed. 2009, 48, 4381; Angew. Chem. 2009, 121, 4445;
d) S. J. Mansfield, C. D. Campbell, M. W. Jones, E. A. Anderson,
Chem. Commun. 2015, 51, 3316.
H insertion of a gold carbene,[22] is unlikely on the basis of the
results with 6 and 9. The general lack of competition from 1,2-
C H insertion of C at adjacent heteroatom-substituted
À
positions (compare the formation of 10 from 9) is surpris-
ing[2,23] and could result from a more concerted polycycli-
zation event (see D), which would also account for the
diastereoinduction at the ring junction in the presence of
a chiral N-substituent (formation of 3j). This interaction is
not, however, required for metal carbene formation by C H
insertion, as seen with 10, in which case 1,2-insertion followed
cyclization.
Attack of the ether oxygen atom or homoallyl group can
lead to competing carbocyclizations of intermediate A
(paths 2 and 3). Although carboalkoxylation is favored at
lower temperatures, a thermal aza-Claisen pathway[24] can
compete at higher temperatures and outperform p-activation
pathways in the absence of a sufficiently electrophilic catalyst
(path 4). A 1,5-hydride shift onto ketenimine H occurs in
À
15528 www.angewandte.org
ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 15525 –15529

Angewandte
Chemie
[5] For examples of reactions with p-systems, see: a) S. Couty, C.
Meyer, J. Cossy, Angew. Chem. Int. Ed. 2006, 45, 6726; Angew.
Chem. 2006, 118, 6878; b) F. Marion, J. Coulomb, C. Courillon,
L. Fensterbank, M. Malacria, Org. Lett. 2004, 6, 1509; c) A. S. K.
Hashmi, M. Rudolph, J. W. Bats, W. Frey, F. Rominger, T. Oeser,
Chem. Eur. J. 2008, 14, 6672; d) S. Kramer, Y. Odabachian, J.
Overgaard, M. Rottländer, F. Gagosz, T. Skrydstrup, Angew.
Chem. Int. Ed. 2011, 50, 5090; Angew. Chem. 2011, 123, 5196; for
examples of reactions with oxidants, see: e) P. W. Davies, A.
Cremonesi, N. Martin, Chem. Commun. 2011, 47, 379; f) C.-W.
Li, K. Pati, G.-Y. Lin, S. A. Sohel, H.-H. Hung, R.-S. Liu, Angew.
Chem. Int. Ed. 2010, 49, 9891; Angew. Chem. 2010, 122, 10087;
g) D. Vasu, H.-H. Hung, S. Bhunia, S. A. Gawade, A. Das, R.-S.
Liu, Angew. Chem. Int. Ed. 2011, 50, 6911; Angew. Chem. 2011,
123, 7043; h) K.-B. Wang, R.-Q. Ran, S.-D. Xiu, C-.Y. Li, Org.
Lett. 2013, 15, 2374; i) R. Liu, G. N. Winston-McPherson, Z.-Y.
Yang, X. Zhou, W. Song, I. A. Guzei, X. Xu, W. Tang, J. Am.
Chem. Soc. 2013, 135, 8201; j) M. D. Santos, P. W. Davies, Chem.
Commun. 2014, 50, 6001; k) L. Li, C. Shu, B. Zhou, Y.-F. Yu, X.-
Y. Xiao, L.-W. Ye, Chem. Sci. 2014, 5, 4057; for examples of
reactions with nitrenoids, see: l) C. Li, L. Zhang, Org. Lett. 2011,
13, 1738; m) P. W. Davies, A. Cremonesi, L. Dumitrescu, Angew.
Chem. Int. Ed. 2011, 50, 8931; Angew. Chem. 2011, 123, 9093;
n) Y. Tokimizu, S. Oishi, N. Fujii, H. Ohno, Org. Lett. 2014, 16,
3138; o) M. Garzón, P. W. Davies, Org. Lett. 2014, 16, 4850;
p) A.-H. Zhou, Q. He, C. Shu, Y.-F. Yu, S. Liu, T. Zhao, W.
Zhang, X. Lu, L.-W. Ye, Chem. Sci. 2015, 6, 1265; q) L. Zhu, Y.
Yu, Z. Mao, X. Huang, Org. Lett. 2015, 17, 30.
[13] CCDC 1410362 (3a) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
[14] For recent examples of gold-catalyst-controlled pathway diver-
gence, see: a) C.-D. Wang, Y.-F. Hsieh, R.-S. Liu, Adv. Synth.
Catal. 2014, 356, 144; b) L.-Y. Mei, Y. Mei, X.-Y. Tang, M. Shi, J.
Am. Chem. Soc. 2015, 137, 8131; c) N. Morita, A. Yasuda, M.
Shibata, S. Ban, Y. Hashimoto, I. Okamoto, O. Tamura, Org.
Lett. 2015, 17, 2668; d) W. Rao, D. Susanti, B. J. Ayers, P. W. H.
Chan, J. Am. Chem. Soc. 2015, 137, 6350; e) G. Xu, C. Zhu, W.
Gu, J. Li, J. Sun, Angew. Chem. Int. Ed. 2015, 54, 883; Angew.
Chem. 2015, 127, 897; for a general review, see: f) J. Mahattha-
nanchai, A. M. Dumas, J. W. Bode, Angew. Chem. Int. Ed. 2012,
51, 10954; Angew. Chem. 2012, 124, 11114.
[15] This result could potentially be due to an aryl – ynamide
interaction; see: C. Wang, X. Xie, J. Liu, Y. Liu, Y. Li, Chem.
Eur. J. 2015, 21, 559.
[16] E. M. Simmons, J. F. Hartwig, Angew. Chem. Int. Ed. 2012, 51,
3066; Angew. Chem. 2012, 124, 3120.
[17] At a 0.27m concentration, 1 f was consumed in 70 min; 72% of
[D]1 f was consumed in 6 h.
À
[18] For indene formation by alkyne insertion into benzylic C H
bonds under Pt/Ru catalysis, see: a) M. Tobisu, H. Nakai, N.
Chatani, J. Org. Chem. 2009, 74, 5471; b) S. Yang, Z. Li, X. Jian,
C. He, Angew. Chem. Int. Ed. 2009, 48, 3999; Angew. Chem.
2009, 121, 4059; c) G. B. Bajracharya, N. K. Pahadi, I. D. Grid-
nev, Y. Yamamoto, J. Org. Chem. 2006, 71, 6204; for Au catalysis,
see: d) P. Morµn-Poladura, E. Rubio, J. M. Gonzµlez, Angew.
Chem. Int. Ed. 2015, 54, 3052; Angew. Chem. 2015, 127, 3095.
[19] Neither substrate proved reactive in the polycyclization. This
result is consistent with a larger angle between the reaction
centers in A/A’ (Scheme 5) for a thiophene scaffold, and
destabilization of the putative cation B by the pyridinyl group.
[20] For an accelerating effect of substitution adjacent to the hydride-
donor site, see: K. Mori, T. Kawasaki, S. Sueoka, T. Akiyama,
Org. Lett. 2010, 12, 1732.
[6] H. V. Adcock, T. Langer, P. W. Davies, Chem. Eur. J. 2014, 20,
7262.
À
[7] For a review on insertion into C X s-bonds, see: H. V. Adcock,
P. W. Davies, Synthesis 2012, 44, 3401.
[8] For impressive super-acid-mediated cationic cascades of aro-
matic ynamides with insertion at unfunctionalized benzylic
positions, see: C. Theunissen, B. MØtayer, N. Henry, G. Compain,
J. Marrot, A. Martin-Mingot, S. Thibaudeau, G. Evano, J. Am.
Chem. Soc. 2014, 136, 12528.
[21] The congested intermediates B/B’ are drawn as if they were
planar, but would be formed in atropisomeric conformations
owing to the stereoelectronic requirements of a sigmatropic or
through-space hydride shift. For a study on the role of rotational
barriers in reaction pathways, see: O. N. Faza, C. S. López, A. R.
de Lera, J. Org. Chem. 2011, 76, 3791.
[22] Y. Horino, T. Yamamoto, K. Ueda, S. Kuroda, F. D. Toste, J. Am.
Chem. Soc. 2009, 131, 2809; S. Bhunia, S. Ghorpade, D. B. Huple,
R.-S. Liu, Angew. Chem. Int. Ed. 2012, 51, 2939; Angew. Chem.
2012, 124, 2993.
À
[9] For reviews on C H insertion, see: a) L. Wang, J. Xiao, Adv.
Synth. Catal. 2014, 356, 1137; b) M. C. Haibach, D. Seidel,
Angew. Chem. Int. Ed. 2014, 53, 5010; Angew. Chem. 2014, 126,
5110; J. Xie, C. Pan, A. Abdukader, C. Zhu, Chem. Soc. Rev.
2014, 43, 5245.
2
2
À
[10] For the formation of C(sp ) C(sp ) bonds from alkynes under
Au catalysis, see: a) I. D. Jurberg, Y. Odabachian, F. Gagosz, J.
Am. Chem. Soc. 2010, 132, 3543; b) J. Barluenga, R. Sigüeiro, R.
Vicente, A. Ballesteros, M. Tomµs, M. A. Rodríguez, Angew.
Chem. Int. Ed. 2012, 51, 10377; Angew. Chem. 2012, 124, 10523;
c) M. M. Hansmann, M. Rudolph, F. Rominger, A. S. K.
Hashmi, Angew. Chem. Int. Ed. 2013, 52, 2593; Angew. Chem.
2013, 125, 2653; d) L. Ye, Y. Wang, D. H. Aue, L. Zhang, J. Am.
Chem. Soc. 2012, 134, 31; e) G. Cera, M. Chiarucci, F. Dosi, M.
Bandini, Adv. Synth. Catal. 2013, 355, 2227; for their formation
under Pt catalysis, see: f) P. A. Vadola, D. Sames, J. Am. Chem.
[23] For a review, see: R. Dorel, A. M. Echavarren, J. Org. Chem.
2015, 80, 7321.
[24] For N-allyl ynesulfonamide aza-Claisen reactions, see: a) K. A.
DeKorver, T. D. North, R. P. Hsung, Synlett 2010, 16, 2397;
b) K. A. Dekorver, R. P. Hsung, A. G. Lohse, Y. Zhang, Org.
Lett. 2010, 12, 1840; c) K. A. DeKorver, W. L. Johnson, Y.
Zhang, R. P. Hsung, H. Dai, J. Deng, A. G. Lohse, Y.-S. Zhang, J.
Org. Chem. 2011, 76, 5092; d) K. A. Dekorver, R. P. Hsung,
A. W.-Z. Song, X.-N. Wang, M. C. Walton, Org. Lett. 2012, 14,
3214; e) X.-N. Wang, G. N. Winston-McPherson, M. C. Walton,
Y. Zhang, R. P. Hsung, K. A. DeKorver, J. Org. Chem. 2013, 78,
6233; f) Y. Zhang, K. A. Dekorver, A. G. Lohse, Y.-S. Zhang, J.
Huang, R. P. Hsung, Org. Lett. 2009, 11, 899; the allylic inversion
in 14b is consistent with the results of these studies.
2
3
À
Soc. 2009, 131, 16525; for the formation of C(sp ) C(sp ) bonds
from alkynes under Au catalysis, see: g) G. Lemi›re, V. Gandon,
N. Agenet, J.-P. Goddard, A. de Kozak, C. Aubert, L. Fenster-
bank, M. Malacria, Angew. Chem. Int. Ed. 2006, 45, 7596;
Angew. Chem. 2006, 118, 7758; for their formation under Pt
catalysis, see: h) D. Vasu, A. Das, R.-S. Liu, Chem. Commun.
2010, 46, 4115.
[25] L. Sun, Y. Zhu, P. Lu, Y. Wang, Org. Lett. 2013, 15, 5894.
[26] X.-Z. Shu, K.-G. Ji, S.-C. Zhao, Z.-J. Zheng, J. Chen, L. Lu, X.-Y.
Lui, Y.-M. Liang, Chem. Eur. J. 2008, 14, 10556.
[11] For a review, see: a) D. Qian, J. Zhang, Chem. Soc. Rev. 2015, 44,
677.
´
[12] A. S. K. Hashmi, J. P. Weyrauch, M. Rudolph, E. Kurpejovic,
Received: August 1, 2015
Angew. Chem. Int. Ed. 2004, 43, 6545; Angew. Chem. 2004, 116,
Revised: September 18, 2015
Published online: October 30, 2015
6707.
Angew. Chem. Int. Ed. 2015, 54, 15525 –15529
ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 15529