Rhodium(III)-Catalyzed Synthesis of Skipped Enynes via C(sp3)–H Alkynylation of Terminal Alkenes

Article abstract of DOI:10.1002/anie.202014877

The Rh^III-catalyzed allylic C?H alkynylation of non-activated terminal alkenes leads selectively to linear 1,4-enynes at room-temperature. The catalytic system tolerates a wide range of functional groups without competing functionalization at other positions. Similarly, the vinylic C?H alkynylation of α,β- and β,γ- unsaturated amides gives conjugated Z-1,3-enynes and E-enediynes.

Full text of DOI:10.1002/anie.202014877

Angewandte
Communications
Chemie
How to cite: Angew. Chem. Int. Ed. 2021, 60, 5693–5698
International Edition: doi.org/10.1002/anie.202014877
German Edition: doi.org/10.1002/ange.202014877
À
C H Activation
Rhodium(III)-Catalyzed Synthesis of Skipped Enynes via C(sp3)–H
Alkynylation of Terminal Alkenes
Franco Della-Felice, Margherita Zanini, Xiaoming Jie, Eric Tan, and Antonio M. Echavarren*
III
À
Abstract: The Rh -catalyzed allylic C H alkynylation of non-
activated terminal alkenes leads selectively to linear 1,4-enynes
at room-temperature. The catalytic system tolerates a wide
range of functional groups without competing functionaliza-
À
tion at other positions. Similarly, the vinylic C H alkynylation
of a,b- and b,g- unsaturated amides gives conjugated Z-1,3-
enynes and E-enediynes.
S
trategies to attain regioselectivity in transition metal-
À
catalyzed C H bond functionalization usually rely on anchi-
meric assistance,[1] either exerted by a pre-existing directing
group or by taking advantage of a transient directing
group.[1d,2] While facing atom- and step-economy challenges,
these approaches have been established as powerful tools for
the production of value-added products from simple precur-
sors,[3] and in the synthesis of advanced pharmaceutical
compounds[4] and natural products.[5] Most methods have
focused on the functionalization of C(sp ) H bonds,[1,6] where
2
À
À
Scheme 1. Different strategies for Rh-catalyzed allylic C H functionali-
zation.
3
À
the more challenging C(sp ) H bond activation strategy have
been growing in the last decade.[1,3c,7]
À
Less common and more ambitious is the selective C H
pling,[15] allylic alkynylation,[16] allylic alkylation,[17] and
nucleophilic substitution.[18]
bond functionalization beyond the aid of directing groups.[8,9]
Recently, [CpxRh] and [CpxIr] complexes have gained atten-
tion in this area due to their ability to coordinate with
terminal double bonds and form p-allyl complexes under mild
conditions.[10] Since the report of Cossy on the formation of
pyrrolidines and tetrahydropyridines by the action of differ-
Grounding from our recent work on C(sp2/sp3)-C(sp)
bond formation,[19] we first investigated the reactivity of hex-
5-en-1-ol (1a) and bromoalkyne 2a with [Cp*RhCl2]2
(5 mol%), AgSbF6 (20 mol%), Ag2CO3 (50 mol%) and
LiOAc (40 mol%) in 1,2-dichloroethane (DCE) at 238C.
Under these mild conditions, we observed formation of
skipped enyne 3a in 47% isolated yield with excellent
stereoselectivity (E/Z > 30:1), moderate linear vs. branched
selectivity and modest linear vs. 1,3-bis alkynylated product
distribution (Table 1, entry 1).[20] The observed linear selec-
tivity in the alkynylation of 1a is noteworthy since internal
ent [Cp*Rh] complexes,[11] other methods have been devel-
x
À
oped for C H bond functionalization via p-allyl [Cp Rh]- and
[CpxIr]-complexes (Scheme 1).[12] Of particular significance
are the findings of Shibata and Tanaka,[10d] Glorious,[10e] and
Baik and Blakey,[10f] where different [CpxRh]-p-allyl com-
plexes where isolated and proved to be catalytically active
À
À
towards allylic C H amination and arylation.
functionalization is typically favored for allylic C H amina-
Here, we report on a directing group-free transformation
for the direct construction of C(sp3)-C(sp) bonds from simple
terminal alkenes under [Cp*Rh]-catalyzed conditions.[13] This
new protocol is suitable for the synthesis of 1,4-enynes from
terminal alkenes without prior functionalization, which are
valuable synthons[14] traditionally prepared by cross cou-
tion[12c] and arylation[21] of non-activated terminal alkenes.
Several observations concerning the optimum reaction
are noteworthy. Using AgOAc instead of LiOAc and Ag2CO3
led to slightly lower conversion (10–15% of unreacted
starting material remained) but formation of the 1,3-bis
alkynylated product was suppressed (Table 1, entry 2). The
higher basicity of Ag2CO3 compared to AgOAc may account
for the small formation of the latter. No reaction was
observed in the absence of LiOAc with substrate 1a, and
either decomposition or no reaction occurred when stoichio-
metric or no AgSbF6 was used, respectively (Table 1, entry 3–
5). The reaction proceeded with lower efficiency when using
[Cp*IrCl2]2 as the catalyst (Table 1, entry 6) and low con-
version was observed in the presence of LiSbF6 (Table 1,
entry 7). Complex Cp*Rh(OAc)2(OH)[22] was inactive in the
absence of AgSbF6 (Table 1, entry 8), although adding LiSbF6
[*] Dr. F. Della-Felice, M. Zanini, Dr. X. Jie, E. Tan, Prof. A. M. Echavarren
Institute of Chemical Research of Catalonia (ICIQ), Barcelona
Institute of Science and Technology
Av. Paꢀsos Catalans 16, 43007 Tarragona (Spain)
E-mail: aechavarren@iciq.es
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202014877.
Angew. Chem. Int. Ed. 2021, 60, 5693 –5698
ꢀ 2021 Wiley-VCH GmbH
5693

Angewandte
Communications
Chemie
À
Table 1: Rh-catalyzed allylic C H alkynylation of 1a with 2.
Other alkyne donors 2b,c resulted in similar conversions but
with lower selectivity (Table 1, entries 10 and 11), which
implies that terminal functionalization is sterically driven.[23]
Next, other alkenes were investigated (Scheme 2). Differ-
ent types of sulfonamides were obtained in good yield and
À
selectivity (3b–e, 3k). It is important to note that no allylic C
Variation
None
R[a] 3a yield [%] L/B L/Bis
H amination was detected with these substrates, a cyclization
that has been reported to occur under similar conditions.[10d,11]
Exclusive linear selectivity was obtained when trying differ-
ent allyl-substituted arenes, as represented by formation of
products 3 f–i. The mildness of the reaction condition allowed
a wide functional group acceptance, including primary halides
(3m, 3t), TBS- and tosyl-masked primary alcohols (3j, 3l),
aliphatic ester (3u), acid (3v), aldehyde (3w), nitro (3z), and
different bromoaryl ethers (3bb–dd). Most interesting,
1
2
3
4
5
6
7
8
9
TIPS
68 (47)
6:1 6:1
With AgOAc, no LiOAc, Ag2CO3 TIPS
60
nr
nr
–
5:1
–
No LiOAc
No AgSbF6
AgSbF6 (120 mol%), no Ag2CO3 TIPS
[Cp*IrCl2]2
LiSbF6
Cp*Rh(OAc)2(OH2), no AgSbF6 TIPS
TIPS
TIPS
[b]
TIPS
TIPS
–
26[c]
nr
–
–
[d]
Cp*Rh(OAc)2(OH2), LiSbF6
TIPS
TES
Ph
61(39)
55
60
8:1 8:1
10
11
None
None
2:1
1:1
–
–
alkenes with an appended aromatic ring bearing directing
groups generally used for the activation of C(sp ) H bonds,
such as a MeO- and -CO2H groups, were selectively function-
alized at the allylic C H position (3h and 3aa) without any
alkynylation at the aromatic ring. Yet, stronger directing
groups as -C(O)(i-Pr)2N and -C(O)NHAc delivered complex
mixtures of mono- and bis alkynylated products.[23] Furane
(3o), thiophene (3p), indole (3q), and pyridine (3r) 1,4-
enynes ester derivatives were as well accessed in good yields
and selectivities. Aromatic alkynylation guided by the ester
moiety was only observed for thiophene 1p, where incorpo-
ration at the activated a-position was detected to a small
2
À
Yields determined by 1H NMR with trichloroethylene as internal
standard. Yields of isolated product in parentheses. [a] 1.2 equiv of 2a–c.
[b] Low conversion observed. [c] Starting material remained. [d] LiSbF6
(40 mol%). L: linear product (3a), B: branched product; Bis: 1,3-bis
product (see Scheme 2). nr: no reaction. DCE: 1,2-dichloroethane.
À
restored the reaction performance with slight better selectiv-
ity (Table 1, entry 9). This last result may suggests a pivotal
role of hexafluoroantimonate salts not only in the activation
of the catalyst but in the activation of the bromoalkyne too.
À
Scheme 2. Substrate scope of allylic C H alkynylation of non-activated terminal alkenes. [a] 63% yield in the absence of LiOAc, 10:1 L/B, 10:1 L/
Bis. [b] Alkynylation at the a-position was also observed.[23] [c] Starting material remained (70% brsm). [d] Reaction performed at 2.5 mmol scale.
[e] 72% yield in the absence of LiOAc, 17:1 L/B, >20:1 L/Bis.
5694 www.angewandte.org
ꢀ 2021 Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 5693 –5698

Angewandte
Communications
Chemie
extent.[23] Polyfunctional complex substrates such as choles-
terol derivative 1x and gibberellic acid ester 1y provided the
desired skipped enynes 3x and 3y, respectively. Although
modest yields were observed, it is worthy to note that the
À
major compound formed originated from the allylic C H
alkynylation of the terminal bond, leaving untouched the
internal and 1,1-disubstituted alkenes. In addition, readily
available alkenes such as n-octane and allylcyclohexane
reacted cleanly to give selectively the corresponding 1,4-
enynes 3n and 3ee in 65% and 68% yield, respectively. This
method is robust, as demonstrated in the preparation of
product 3bb from 1bb in a 2.5 mmol scale in comparable yield
and selectivity.[23]
Interestingly, products 3l and 3ee were obtained in similar
yields in the presence or in the absence of LiOAc, whereas the
use of this salt was essential for the formation of compounds
3a, 3b or 3 f. This suggest that LiOAc might be necessary to
prevent formation of inactive RhIII species in cases in which
the substrate bears potentially coordinating groups.[24]
1,3-Bisalkynylation was promoted after a consecutive set
up and products 4a–d could be accessed in moderate to good
yields and selectivity (Scheme 3).[20] In this case, formation of
1,1-bis- and 1,4-bisalkynylated compounds were observed as
minor products.
Scheme 4. a) DFT calculations for the RhIII-catalyzed alkynylation of
alkenes [wB97xD/6–311G+ +(d,p)(H, C, O, Si) + LANL2DZ(d)(Br) +
LANL2TZ-(f)(Rh, Ag)// 6-31G(d)(H, C, O, Si) + LANL2DZ(Rh, f; Ag, f;
Br, d)]. b) Proposed catalytic cycle.
[23]
Scheme 3.
Substrate scope of 1,3-bisalkynylation of non-activated
terminal bonds. Reaction conditions: 2a (110 mol%), [Cp*RhCl2]2
(5 mol%), AgSbF6 (20 mol%), Ag2CO3 (50 mol%), LiOAc (40 mol%),
DCE (0.2 M), 238C, 16 h. [a] Starting from 3l.
state. This result is in excellent agreement with the observed
regioselectivity for 1ee (> 20:1). Following the preferred
mechanistic pathway, a catalytic cycle for the formation of
skipped enynes is proposed in Scheme 4b. First, formation of
complex I by interaction of 1ee and 2a with [Cp*RhCl2]2,
AgOAc and AgSbF6, is followed by g-migratory insertion
towards II. The latter is then stabilized to III by coordination
of AgOAc, and a b-bromo-elimination is promoted forming
product 3ee and AgBr. A new molecule of 1ee enters
Density functional theory calculations25 where under-
taken to better understand the operative mechanism of this
transformation (Scheme 4). Using 1ee as the substrate and
AgOAc as the additive, the activation barriers of migratory
insertion/b-elimination and oxidative addition/reductive
elimination pathways were compared (Scheme 4a).[10,11]
Starting from p-allyl Int1, analogous to known catalytically
À
producing IV, and starts the cycle after C H allylic activation
and complexation with 2a.
active RhIII-intermediates in C H allylic functionaliza-
À
tion,[10d–f] coordination with 2a can generate Int2A and
Int2B. Next, the theoretical results suggested that terminal
functionalization by g-migratory insertion towards Int3
(DG° = 25.2 kcalmolÀ1) would be kinetically favored over
the formation of the RhV species Int4 (DG° = 32.8 kcal
molÀ1), an intermediate that upon reductive elimination
would also lead to the linear product. a-Migratory insertion
was as well calculated for 1ee and proved to be kinetically
disfavored compared to g-migration (DG° = 34.8 kcalmolÀ1),
presumably by an increase of steric hindrance at the transition
The catalytic system employed was also compatible for
the formation of C(sp2)-C(sp) bonds.[19b] Observing that
terminal alkenes with appended tosyl amides were well
À
tolerated in the undirected allylic C H alkynylation and
arylamides were unreactive,[23] a slightly modified protocol
was tested with terminal alkenes having amide groups at
different distances from the carboxamide. Thus, we found that
b,g-unsaturated amides 5a–c were bisalkynylated and form
conjugated E-enediynes 6a–c, (Scheme 5a). Interestingly,
trans-5d led to E-configured 1,3-enyne 7, although in
Angew. Chem. Int. Ed. 2021, 60, 5693 –5698
ꢀ 2021 Wiley-VCH GmbH
www.angewandte.org
5695

Angewandte
Communications
Chemie
functional groups, including known aryl-directing groups
without functionalization at the aromatic ring. Theoretical
experiments suggested a migratory insertion mechanism to be
kinetically favored against an oxidative addition/reductive
elimination pathway. 1,3-Bisalkynylation was also accessed
and may be complementary to known 1,1-bisalkynylation
procedures. Finally, a,b- and b,g-unsaturated amides give Z-
1,3-enynes and E-bis-enediynes, respectively.[31]
Acknowledgements
We thank the Ministerio de Ciencia e Innovaciꢀn (PID2019-
104815GB-I00), Severo Ochoa Excellence Accreditation
2020-2023 (CEX2019-000925-S), La Caixa-Severo Ochoa
predoctoral fellowship to M.Z, H2020-Marie Sklodowska-
Curie contract to X.J.L.P. (Grant Agreement 792649), the
AGAUR (2017 SGR 1257), and CERCA Program/General-
itat de Catalunya for financial support.
À
Scheme 5. Substrate scope of vinyl C H alkynylation of activated and
non-activated alkene bonds. Reaction conditions: 2a (250 mol%),
[Cp*RhCl2]2 (3 mol%), AgSbF6 (24 mol%), Ag2CO3 (100 mol%), LiOAc
(100 mol%), DCE, 808C, 16 h. [a] 1008C.
modest yield. On the other hand, a,b-unsaturated amides 5e–
i were mono-alkynylated giving stereoselectively Z-1,3-
enynes 8a–e in moderate yields (Scheme 5b).[26] A different
outcome was observed with 2-phenylacetamide 5j, which
gave exclusively ortho-alkynyl 9 in 60% yield (Scheme 5c).
Pivalanilides led to the expected products of ortho-alkynyla-
tion under these reaction conditions.[23,27]
Conflict of interest
The authors declare no conflict of interest.
Keywords: 1,4-enynes · alkynylation · allylic functionalization ·
À
To illustrate the synthetic utility of the obtained 1,3- and
1,4-enynes, further transformations were conducted
(Scheme 6). Deprotection of 3bb with stoichiometric TBAF
(100 mol%) led to the corresponding terminal alkyne in 65%
yield, which was converted to the b,g-unsaturated enone 10 in
70% yield when exposed to [t-BuXPhosAu(MeCN)]BArF in
methanol. Alternatively, treatment of 3bb with excess TBAF
(250 mol%) afforded the respective conjugated allene in
86% yield,[28] and underwent a [4+2] cycloaddtion with
methyl vinyl ketone to give adduct 11 in 61% yield (endo:
4:1).[29] Moreover, 1,3-enyne 8a delivered pyrrolone 12 in
92% yield after TBAF treatment.[30]
rhodium · undirected C H activation
À
[1] For representative reviews on directing group-assisted C H
functionalization, see: a) Z. Chen, B. Wang, J. Zhang, W. Yu, Z.
Liu, Y. Zhang, Org. Chem. Front. 2015, 2, 1107 – 1295; b) Sam-
biagio, D. Schçnbauer, R. Blieck, T. Dao-Huy, G. Pototschnig, P.
Schaaf, T. Wiesinger, M. F. Zia, J. Wencel-Delord, T. Besset,
B. U. W. Maes, M. Schnꢁrch, Chem. Soc. Rev. 2018, 47, 6603 –
6743; c) L. D. Caspers, B. J. Nachtsheim, Chem. Asian J. 2018, 13,
1231 – 1247; d) O. K. Rasheed, B. Sun, ChemistrySelect 2018, 3,
5689 – 5708; e) M. Kapoor, A. Singh, K. Sharma, M. Hua Hsu,
Adv. Synth. Catal. 2020, 362, 4513 – 4542.
In summary, we have developed a [Cp*Rh]-catalyzed
[2] For selected reviews on transient directing groups, see: a) Q.
Zhao, T. Poisson, X. Pannecoucke, T. Besset, Synthesis 2017, 49,
4808 – 4826; b) P. Gandeepan, L. Ackermann, Chem 2018, 4,
199 – 222; c) T. Bhattacharya, S. Pimparkar, D. Maiti, RSC Adv.
2018, 8, 19456 – 19464; For selected recent examples on remote
À
linear selective allylic C H bond alkynylation under mild
conditions allowing straightforward access to synthetically
usefull 1,4-enynes. This reaction tollerates a broad range of
À
C H bond functionalization, see: d) H. Shi, Y. Lu, J. Weng, K. L.
Bay, X. Chen, K. Tanaka, P. Verma, K. N. Houk, J. Q. Yu, Nat.
Chem. 2020, 12, 399 – 404; e) R. R. Annapureddy, C. Jandl, T.
Bach, J. Am. Chem. Soc. 2020, 142, 7374 – 7378.
[3] For reviews, see: a) R. H. Crabtree, J. Chem. Soc. Dalton Trans.
2001, 2437 – 2450; b) J. A. Labinger, J. E. Bercaw, Nature 2002,
417, 507 – 514; c) R. Jazzar, J. Hitce, A. Renaudat, J. Sofack-
Kreutzer, O. Baudoin, Chem. Eur. J. 2010, 16, 2654 – 2672; d) J.
Zhang, L. J. Kang, T. C. Parker, S. B. Blakey, C. K. Luscombe,
S. R. Marder, Molecules 2018, 23, 922; e) S. Yuan, Y. Li, J. Peng,
Y. M. Questell-Santiago, K. Akkiraju, L. Giordano, D. J. Zheng,
S. Bagi, Y. Romꢂn-Leshkov, Y. Shao-Horn, Adv. Energy Mater.
2020, 10, 2002154; f) S. Shaaban, C. Davies, H. Waldmann, Eur. J.
Org. Chem. 2020, 6512 – 6524.
[4] For reviews, see: a) J. Yamaguchi, A. D. Yamaguchi, K. Itami,
Angew. Chem. Int. Ed. 2012, 51, 8960 – 9009; Angew. Chem.
2012, 124, 9092 – 9142; b) E. J. E. Caro-Diaz, M. Urbano, D. J.
Buzard, R. M. Jones, Bioorg. Med. Chem. Lett. 2016, 26, 5378 –
5383; c) J. Yamaguchi, K. Amaike, K. Itami in Transition Metal
À
Scheme 6. Derivatization of 1,4-enynes from C H alkynylation. Ar: 4-
Br-C6H4.
5696 www.angewandte.org
ꢀ 2021 Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 5693 –5698

Angewandte
Communications
Chemie
À
Heterocycle Synthesis via C H Activation (Ed.: X.-F. Wu),
Wiley-VCH, Weinheim, 2016, pp. 505 – 550; d) D. Basu, S.
Kumar, V. SaiSudhir, R. Bandichhor, J. Chem. Sci. 2018, 130,
71; e) M. Moir, J. J. Danon, T. A. Reekie, M. Kassiou, Expert
Opin. Drug Discovery 2019, 14, 1137 – 1149.
M. Kanai, J. Am. Chem. Soc. 2017, 139, 4647 – 4650; d) X. Fang,
Q. Li, R. Shi, H. Yao, A. Lin, Org. Lett. 2018, 20, 6084 – 6088.
[15] For systematic studies on 1,4-enyne formation by cross-coupling,
see: a) A. Commercon, J. Normant, J. Villieras, J. Organomet.
Chem. 1975, 93, 415 – 421; b) T. P. Heffron, J. D. Trenkle, T. F.
Jamison, Tetrahedron 2003, 59, 8913 – 8917; c) M. Shirakura, M.
Suginome, Angew. Chem. Int. Ed. 2010, 49, 3827 – 3829; Angew.
Chem. 2010, 122, 3915 – 3917; d) R. Agata, S. Lu, H. Matsuda, K.
Isozaki, M. Nakamura, Org. Biomol. Chem. 2020, 18, 3022 –
3026.
[16] For recent systematic studies on 1,4-enyne formation by allylic
alkynylation, see: a) A. Harada, Y. Makida, T. Sato, H. Ohmiya,
M. Sawamura, J. Am. Chem. Soc. 2014, 136, 13932 – 13939; b) Q.
Yang, Y. Zhou, J. Chen, X. He, J. Xu, F. Y. Kwong, B. Fan, Eur. J.
Org. Chem. 2015, 5330 – 5333; c) T. Nakane, Y. Tanioka, N.
Tsukada, Organometallics 2015, 34, 1191 – 1196; d) P. Xie, Z.
Sun, S. Li, L. Zhang, X. Cai, W. Fu, X. Yang, Y. Liu, X. Wo, T. P.
Loh, Org. Lett. 2020, 22, 1599 – 1604.
[17] For selected systematic studies on 1,4-enyne formation by allylic
alkylation, see a) B. M. Trost, S. Hildbrand, K. Dogra, J. Am.
Chem. Soc. 1999, 121, 10416 – 10417; b) R. Takeuchi, K. Tanabe,
Angew. Chem. Int. Ed. 2000, 39, 1975 – 1978; Angew. Chem.
2000, 112, 2051 – 2054; c) M. A. Kacprzynski, A. H. Hoveyda, J.
Am. Chem. Soc. 2004, 126, 10676 – 10681; d) N. F. Langille, T. F.
Jamison, Org. Lett. 2006, 8, 3761 – 3764; e) H. Li, A. Alexakis,
Angew. Chem. Int. Ed. 2012, 51, 1055 – 1058; Angew. Chem.
2012, 124, 1079 – 1082; f) Y. Makida, Y. Takayama, H. Ohmiya,
M. Sawamura, Angew. Chem. Int. Ed. 2013, 52, 5350 – 5354;
Angew. Chem. 2013, 125, 5458 – 5462.
[18] For systematic studies on 1,4-enyne formation nucleophilic
substitution, see: a) S. Peng, L. Wang, J. Wang, Org. Biomol.
Chem. 2012, 10, 225 – 228; b) G. Huang, X. Wang, Y. Pan, H.
Wang, G. Yao, Y. Zhang, J. Org. Chem. 2013, 78, 2742 – 2745.
[19] a) E. Tan, A. I. Konovalov, G. A. Fernandez, R. Dorel, A. M.
Echavarren, Org. Lett. 2017, 19, 5561 – 5564; b) E. Tan, O.
Quinonero, M. E. de Orbe, A. M. Echavarren, ACS Catal. 2018,
8, 2166 – 2172; c) E. Tan, M. Zanini, A. M. Echavarren, Angew.
Chem. Int. Ed. 2020, 59, 10470 – 10473; Angew. Chem. 2020, 132,
10556 – 10559.
[5] For reviews, see: a) K. Godula, D. Sames, Science 2006, 312, 67 –
72; b) W. R. Gutekunst, P. S. Baran, Chem. Soc. Rev. 2011, 40,
1976 – 1991; c) D. Y. K. Chen, S. W. Youn, Chem. Eur. J. 2012, 18,
9452 – 9474; d) P. Tao, Y. Jia, Sci. China Chem. 2016, 59, 1109 –
1125; e) K. Chen, X. Lei, Curr. Opin. Green Sustain. Chem. 2018,
11, 9 – 14; f) S. K. Sinha, G. Zanoni, D. Maiti, Asian J. Org.
Chem. 2018, 7, 1178 – 1192; g) H. Zhai, Y. Li, F. Fang in
Efficiency in Natural Product Total Synthesis (Eds.: P.-Q.
Huang, Z.-J. Yao, R. P. Hsung), Wiley, Hoboken, 2018,
pp. 261 – 272; h) D. J. Abrams, P. A. Provencher, E. J. Sorensen,
Chem. Soc. Rev. 2018, 47, 8925 – 8967.
[6] For reviews, see; a) G. Song, F. Wang, X. Li, Chem. Soc. Rev.
2012, 41, 3651 – 3678; b) G. Song, X. Li, Acc. Chem. Res. 2015, 48,
1007 – 1020; c) S. Rej, N. Chatani, Angew. Chem. Int. Ed. 2019,
58, 8304 – 8329; Angew. Chem. 2019, 131, 8390 – 8416; d) M. R.
Sk, S. S. Bera, S. Basuli, A. Metya, M. S. Maji, Asian J. Org.
Chem. 2020, 9, 1701 – 1717.
[7] For reviews, see: a) T. G. Saint-Denis, R. Y. Zhu, G. Chen, Q. F.
Wu, J. Q. Yu, Science 2018, 359, eaao4798; b) J. C. K. Chu, T.
Rovis, Angew. Chem. Int. Ed. 2018, 57, 62 – 101; Angew. Chem.
2018, 130, 64 – 105.
À
[8] For an outlook on undirected C H functionalization, see: a) J. F.
Hartwig, M. A. Larsen, ACS Cent. Sci. 2016, 2, 281 – 292; for
À
recent examples on undirected C H functionalization, see: b) A.
Mondal, H. Chen, L. Flꢃmig, P. Wedi, M. Van Gemmeren, J. Am.
Chem. Soc. 2019, 141, 18662 – 18667; c) R. Oeschger, B. Su, I. Yu,
C. Ehinger, E. Romero, S. He, J. Hartwig, Science 2020, 368,
736 – 741.
[9] For representative reviews on undirected Pd-catalyzed p-allyl
À
C H bond functionalization of non-activated alkenes, see:
a) C. J. Engelin, P. Fristrup, Molecules 2011, 16, 951 – 969; b) A.
Breder, Synlett 2014, 25, 899 – 904; c) F. Liron, J. Oble, M. M.
Lorion, G. Poli, Eur. J. Org. Chem. 2014, 5863 – 5883; d) R. A.
Fernandes, J. L. Nallasivam, Org. Biomol. Chem. 2019, 17, 8647 –
8672.
[20] For the selective formation of 1,1-bis alkylation compounds, see:
Y. Li, H. Wei, D. Wu, Z. Li, W. Wang, G. Yin, ACS Catal. 2020,
10, 4888 – 4894.
[10] For literature related to isolated CpXM (M = Rh, Ir) complexes,
see: a) R. A. Periana, R. G. Bergman, J. Am. Chem. Soc. 1984,
106, 7272 – 7273; b) J. B. Wakefield, J. M. Stryker, J. Am. Chem.
Soc. 1991, 113, 7057 – 7059; c) Y. F. Han, G. X. Jin, Chem. Soc.
Rev. 2014, 43, 2799 – 2823; d) Y. Shibata, E. Kudo, H. Sugiyama,
H. Uekusa, K. Tanaka, Organometallics 2016, 35, 1547 – 1552;
e) A. Lerchen, T. Knecht, M. Koy, J. B. Ernst, K. Bergander,
C. G. Daniliuc, F. Glorius, Angew. Chem. Int. Ed. 2018, 57,
15248 – 15252; Angew. Chem. 2018, 130, 15468 – 15472; f) R. J.
Harris, J. Park, T. A. F. Nelson, N. Iqbal, D. C. Salgueiro, J.
Bacsa, C. E. Macbeth, M. H. Baik, S. B. Blakey, J. Am. Chem.
Soc. 2020, 142, 5842 – 5851.
[21] To the best of our knowledge, linear selectivity in Cp*RhIII
-
catalyzed allyl-aryl coupling is only favored in systems in which
the final alkene is conjugated to an aryl ring: a) ref. [10e]; b) T.
Knecht, T. Pinkert, T. Dalton, A. Lerchen, F. Glorius, ACS Catal.
2019, 9, 1253 – 1257.
[22] a) P. M. Boyer, C. R. Roy, J. M. Bielski, J. S. Merola, Inorg.
Chim. Acta 1996, 245, 7 – 15; b) G. A. M. Jardim, E. N. Da Silva,
J. F. Bower, Chem. Sci. 2016, 7, 3780 – 3784.
[23] See the Supporting Information for additional details.
[24] For the role of acetate in the cyclometallation with [Cp*RhCl2]2,
[Cp*IrCl2]2, and [RuCl2(p-cymene)]2, see: D. L. Davies, O. Al-
Duaij, J. Fawcett, M. Giardiello, S. T. Hilton, D. R. Russell,
Dalton Trans. 2003, 4132 – 4138.
[11] T. Cochet, V. Bellosta, D. Roche, J. Y. Ortholand, A. Greiner, J.
Cossy, Chem. Commun. 2012, 48, 10745 – 10747.
[12] a) A. Archambeau, T. Rovis, Angew. Chem. Int. Ed. 2015, 54,
13337 – 13340; Angew. Chem. 2015, 127, 13535 – 13538; b) Q.
Cui, W. Liao, Z. Y. Tian, Q. Li, Z. X. Yu, Org. Lett. 2019, 21,
7692 – 7696; c) T. A. F. Nelson, M. R. Hollerbach, S. B. Blakey,
Dalton Trans. 2020, 49, 13928 – 13935.
[13] For the preparation of 1,4-enynes from non-activated alkenes,
see: a) X. Le Zhou, L. Ren, P. S. Wang, J. Org. Chem. 2017, 82,
9794 – 9800; b) A. A. Almasalma, E. Mejꢄa, Chem. Eur. J. 2018,
24, 12269 – 12273.
[25] See the Supporting Information for all the computational details
and the complete study.
[26] Substrate 5d also delivered 8d’ in 7% yield under these
conditions.[23]
[14] For selected systematic studies on transformations of 1,4-enynes,
see: a) A. Buzas, F. Gagosz, J. Am. Chem. Soc. 2006, 128, 12614 –
12615; b) S. Gao, H. Liu, C. Yang, Z. Fu, H. Yao, A. Lin, Org.
Lett. 2017, 19, 4710 – 4713; c) X. F. Wei, X. W. Xie, Y. Shimizu,
Angew. Chem. Int. Ed. 2021, 60, 5693 –5698
ꢀ 2021 Wiley-VCH GmbH
www.angewandte.org
5697

Angewandte
Communications
Chemie
[27] For directed ortho-alkynylation of anylines, see: a) R. Amemiya,
A. Fujii, M. Yamaguchi, Tetrahedron Lett. 2004, 45, 4333 – 4335;
b) M. Tobisu, Y. Ano, N. Chatani, Org. Lett. 2009, 11, 3250 –
3252; c) F. Xie, Z. Qi, S. Yu, X. Li, J. Am. Chem. Soc. 2014, 136,
4780 – 4787; d) Z. Ruan, S. Lackner, L. Ackermann, ACS Catal.
2016, 6, 4690 – 4693.
[31] Since acceptance of this manuscript, a related study was
published: S. Mondal, T. Pinkert, C. G. Daniliuc, F. Glorius,
Angew. Chem. Int. Ed. 2021, https://doi.org/10.1002/anie.
202015249; Angew. Chem. 2021, https://doi.org/10.1002/ange.
202015249.
[28] For the preparation of related conjugated allenes, see ref. [20].
[29] K. Yoshida, P. A. Grieco, Chem. Lett. 1985, 14, 155 – 158.
[30] a) Y. Hoshino, Y. Shibata, K. Tanaka, Angew. Chem. Int. Ed.
2012, 51, 9407 – 9411; Angew. Chem. 2012, 124, 9541 – 9545; b) C.
Feng, D. Feng, Y. Luo, T. P. Loh, Org. Lett. 2014, 16, 5956 – 5959.
Manuscript received: November 6, 2020
Revised manuscript received: December 24, 2020
Accepted manuscript online: January 6, 2021
Version of record online: February 1, 2021
5698 www.angewandte.org
ꢀ 2021 Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 5693 –5698