Rhodium-Catalyzed Branched and Enantioselective Direct α-Allylic Alkylation of Simple Ketones with Alkynes

Article abstract of DOI:10.1021/acs.orglett.0c00375

Herein, we report the first direct branched-selective α-allylic alkylation of simple ketones with alkynes under rhodium and secondary amine cooperative catalysis. Through a rhodium-hydride-catalyzed allylic substitution pathway, a series of valuable γ,δ-unsaturated ketones are obtained with excellent regioselectivity in an atom-economic and byproduct-free manner. With a chiral BIPHEP ligand, high enantioselectivity has been achieved for this transformation.

Full text of DOI:10.1021/acs.orglett.0c00375

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Letter
Rhodium-Catalyzed Branched and Enantioselective Direct α‑Allylic
Alkylation of Simple Ketones with Alkynes
Liyu Xie, Haijian Yang, Mingliang Ma, and Dong Xing*
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ABSTRACT: Herein, we report the first direct branched-selective
α-allylic alkylation of simple ketones with alkynes under rhodium
and secondary amine cooperative catalysis. Through a rhodium−
hydride-catalyzed allylic substitution pathway, a series of valuable
γ,δ-unsaturated ketones are obtained with excellent regioselectivity
in an atom-economic and byproduct-free manner. With a chiral
BIPHEP ligand, high enantioselectivity has been achieved for this transformation.
ransition-metal-catalyzed asymmetric allylic alkylation
(AAA) is one of the most important and powerful methods
of a leaving group is still unavoidable. From economic and
environmental perspectives,9 the development of atom-
economic and byproduct-free α-allylic alkylation of ketones
with high levels of asymmetric induction is of great synthetic
importance.
T
for the construction of C−C bonds with stereocenters.1 Among
them, the asymmetric α-allylic alkylation of ketones serves as an
efficient and reliable strategy to access chiral ketone motifs.2
Conventionally, the use of unstabilized enolates, either
preformed or in-situ-generated with stoichiometric amounts of
strong metallic bases (i.e., LDA, LiHMDS), is generally required
to react with electrophilic allyl agents for the regio- and
enantioselective α-allylic alkylation of ketones.2−4 In this
context, by utilizing Pd or Ir catalysis, highly branched and
enantioselective α-allylic alkylation of ketones, which gives
synthetically valuable β-branched γ,δ-unsaturated ketone
motifs,5 has been extensively studied (Scheme 1A).4 Although
Recently, there has been an emerging research interest in the
use of methyl alkynes as atom-economic precursors for the
generation of electrophilic metal π-allyl species.10 Since Trost11
and Yamamoto’s12 seminal reports, a series of transition-metal-
catalyzed alkyne-mediated allylic substitutions have been
developed by Breit,13 Dong,14 and others.15 Within this context,
whereas different types of functionalized ketones, such as 1,3-
diketones,13a,15a β-keto esters,13b or β-keto acids,13c,14a have
been applied as the nucleophiles for efficient C−C bond
formations, the direct α-allylic alkylation of simple and
unfunctionalized ketones with internal alkynes remained
unknown until the recent report by Lin, in which a palladium/
proline cooperative catalysis was utilized for the α-allylic
alkylation of cyclic ketones.15b In 2018, Zhao’s group realized
the enantioselective version of this transformation.15d For both
reports, linear selectivity was achieved, and only cyclic ketones
were suitable substrates. To the best of our knowledge, direct
branched-selective α-allylic alkylation of simple ketones with
alkynes remained an unknown transformation. Herein, we
report the development of a Rh-catalyzed branched-selective α-
allylic alkylation of both cyclic and acyclic simple ketones with
methyl alkynes in a highly atom-economic and byproduct-free
manner (Scheme 1B). A rhodium/secondary amine cooperative
catalytic system in the presence of a Brønsted acid catalyst is
responsible for not only the formation of an electrophilic π-allyl
species from alkyne10a but also the in situ generation of a
Scheme 1. Intermolecular Coupling of Simple Ketones with
Internal Alkynes
effective, the formation of stoichiometric metal salts and
conjugate acids of the bases as byproducts is the major drawback
of these approaches. To overcome this, secondary amine, which
would generate a Stork enamine in situ, has been utilized as the
cocatalyst for asymmetric α-allylic alkylation of ketones with
allyl agents.6,7 However, most of these transformations gave
linear selectivity,8 and the liberation of a stoichiometric amount
Received: January 29, 2020
https://dx.doi.org/10.1021/acs.orglett.0c00375
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

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Letter
nucleophilic enamine species from ketone. Efficient intercept of
the enamine intermediate by the π-allyl intermediate would then
happen to yield the α-allylic alkylation product. We envisioned
that the key for the branched-selective control of the
transformation would lie in the suitable combination of the
rhodium(I) precatalyst and the amine cocatalyst for both the
reactivity and stereocontrol.
We initiated our investigation using cyclopentanone (1a) and
1-phenyl-1-propyne (2a) as the model substrates. A variety of
rhodium precatalysts, ligands, secondary amine catalysts, acid
catalysts, additives, and solvents were examined. Ultimately, in
the presence of 5 mol % of [Rh(cod)Cl]2, 10 mol % of 2,2′-
bis(diphenylphosphino)-1,1′-biphenyl (BIPHEP) ligand, 25
mol % of morpholine, 10 mol % of diphenyl phosphate, and
50 mol % of 2,6-dimethylphenol (DMP) in 1,2-dichloroethane
(DCE), the desired α-allylic alkylation product (3a) was
obtained in 93% isolated yield with excellent branched
selectivity (Table 1, entry 1). To understand the role of each
yield and BINAP also showed moderate catalytic activity (Table
1, entry 10); ligands with large bite angles (e.g., dppb, dppf, and
DIOP) showed poor reactivities (Table 1, entries 11−13).
With the optimized reaction conditions in hand, we next
sought to explore the generality of this transformation. The
scope of alkynes was studied first (Scheme 2). Both electron-rich
a
Scheme 2. Substrate Scope of Methyl Alkynes
a
Table 1. Condition Optimizations
b
b
entry
variant from standard conditions
none
without morpholine
pyrrolidine instead of morpholine
piperidine instead of morpholine
without (PhO)2POOH
PhCOOH instead of (PhO)2POOH
TsOH instead of (PhO)2POOH
Ph2POOH instead of (PhO)2POOH
without 2,6-DMP
yield (%)
dr of 3a
d
1
2
3
4
5
6
7
8
9
10
11
12
13
94 (93)
<5
72
52
<5
24
7
41
80
51
12
6
1.2:1
a
1.2:1
1.3:1
All reactions were run on a 0.2 mmol scale of 1a, 1a/2 = 1:1.25; all
yields are isolated yields; diastereoselectivity ratio (dr) was
1
determined by H NMR of the reaction mixture.
1.0:1
1.3:1
1.1:1
1.2:1
1.1:1
1.1:1
1.1:1
1.2:1
(3b−d) and electron-deficient (3f and 3g) para-substituted aryl
alkynes reacted efficiently. Electronically distinct ortho- and
meta-substituted aryl alkynes also worked well (3h−j). Halogen
substituents such as fluoride (3f and 3j) and chloride (3g) were
tolerated. In addition, 2-naphthyl alkyne or a 1,4-dioxane-fused
aryl alkyne were suitable substrates, yielding the corresponding
products in good efficiency (3k and 3l).
BINAP instead of BIPHEP
dppb instead of BIPHEP
dppf instead of BIPHEP
DIOP instead of BIPHEP
15
a
Unless otherwise noted, the reaction was run on a 0.2 mmol scale of
b
1
The scope of ketones was then investigated (Scheme 3).
Cyclic ketones generally showed high efficiency. Cyclo-
hexanone, 4-phenyl, or 4,4-dimethyl cyclohexanone all reacted
smoothly to give desired α-allylic alkylation products (4a−c). β-
Tetralone underwent the desired α-allylic alkylation exclusively
at the benzylic position (4d). Compared with cyclic ketones,
acyclic ketones are unsurprisingly much less reactive. Encourag-
ingly, by increasing the amount of ketone to 3 equiv with
prolonged reaction time (72 h), the desired α-allylic alkylation
products were successfully obtained exclusively at the less
hindered α-methyl position, albeit with decreased reactivity.16
With this slightly modified protocol, 2-pentanone, 4-methyl-2-
pentanone, and acetone were coupled with alkyne 1a to provide
the corresponding α-allylic alkylation products (4e−g).
Acetophenone, as well as several electronically distinct
substituted acetophenones, also worked well, yielding the
corresponding products in moderate yields (4h−k). A
cholestanone-derived α-allylic alkylation product (4l) was
obtained with this method.
1a, 1a/2a = 1:1.25. Yield determined by H NMR using 1,1,2,2-
tetrachloroethane as the internal standard. Diastereoselectivity ratio
(dr) was determined by H NMR of the reaction mixture. Isolated
yield in parentheses.
c
d
1
reactant, a series of control experiments were conducted. The
reaction did not proceed in the absence of a secondary amine
cocatalyst, indicating its crucial role in converting the ketone
substrate into a more nucleophilic Stork enamine intermediate
in situ (Table 1, entry 2). Pyrrolidine and piperidine could also
be used as the cocatalyst, but decreased reactivities were
observed (Table 1, entries 3 and 4). The acid cocatalyst was also
indispensable and may be responsible for not only the
generation of the requisite Rh−H catalyst but also the enamine
formation (Table 1, entry 5). Diphenyl phosphate showed
superior reactivity among different acids being tested (Table 1,
entries 6−8). In the absence of 2,6-DMP, the efficiency of this
reaction is decreased (Table 1, entry 9). Although it is still
unclear, 2,6-DMP may play a role in facilitating the acid-
catalyzed enamine formation by suppressing the formation of
the self-aldol side product of cyclopentanone 1a. Among various
bidentate phosphine ligands tested, BIPHEP gave the highest
The feasibility of the γ,δ-unsaturated ketone product was
demonstrated by a three-step synthesis of bicyclic pyridine 7
from 3a in a 62% overall yield (Scheme 4).17
B
https://dx.doi.org/10.1021/acs.orglett.0c00375
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Letter
a
Scheme 3. Substrate Scope of Ketones
Scheme 5. Ligand Effects for the Enantioselective α-Allylic
Alkylation between 1a and 2a
a
a
Unless otherwise noted, the reaction was run on a 0.2 mmol scale of
1a, 1a/2a = 1:1.25; all yields are isolated yields; diastereoselectivity
ratio (dr) was determined by 1H NMR of the reaction mixture;
enantioselectivity ratio (er) was determined by chiral HPLC analysis.
Scheme 6. Substrate Scope for the Enantioselective α-Allylic
a
Alkylation
a
For cyclic ketones, the reactions were run on a 0.2 mmol scale of 1,
1/2a = 1:1.25; for acyclic ketones, the reactions were run on a 0.2
mmol scale of 2a for 72 h, 1/2a = 3:1; all yields are isolated yields;
diastereoselectivity ratio (dr) was determined by 1H NMR of the
reaction mixture.
Scheme 4. Synthetic Elaboration of 3a
a
For cyclic ketones, the reactions were run on a 0.2 mmol scale of 1,
1/2 = 1:1.25; for acyclic ketones, the reactions were run on a 0.2
mmol scale of 2, 1/2 = 3:1; all yields are isolated yields;
diastereoselectivity ratio (dr) was determined by 1H NMR of the
reaction mixture; enantioselectivity ratio (er) was determined by
chiral HPLC analysis.
To further expand the synthetic utility of this protocol, we
sought to realize the enantioselective control of this trans-
formation (Scheme 5). As BIPHEP was proven to be the best
ligand in racemic reactions, several BIPHEP-derived chiral
ligands were evaluated. Simple chiral (S)-MeO-BIPHEP ligand
(L1) gave the desired products with moderate enantioselectiv-
ities. Increasing the steric bulk of the phosphine substituent
improved the enantioselectivities (L2, L3, and L4), and the
highest enantioselectivities were achieve with the most steric
and electron-rich (S)-DTBM-MeO-BIPHEP ligand (L4).
Chiral ligands with similar biphenyl backbones such as (S)-
DTBM-SEGPHOS (L5) or (S)-BINAP (L6) also gave good
enantioselectivities but were less effective than L4. By using (S)-
DTMB-MeO-BIPHEP (L4) as the ligand, decreasing the
reaction temperature from 110 to 70 °C with a prolonged
reaction time (from 24 to 72 h) allowed further improved
enantioselectivities while the reaction remained efficient
(Scheme 6, ent-3a).
Several ketone substrates were subjected to the optimized
enantioselective conditions. Cyclohexanone also showed high
reactivity and enantioselectivities (ent-4a). Acyclic ketones were
then tested. Given their moderate reactivities, 2-petanone as well
as several aryl methyl ketones could also be directly converted
into the corresponding products with good enantioselectivities
[(R)-4e, 4h−4j].18,19
Methyl alkyne is generally considered as the precursor of an
allene for the generation of the π-allylmetal species. To test the
involvement of an allene intermediate for this transformation,
phenylallene 8 was prepared and allowed to react with
cyclopentanone 1a under standard reaction conditions (eq 1).
The desired α-allylic alkylation product ent-3a was obtained with
C
https://dx.doi.org/10.1021/acs.orglett.0c00375
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
Mingliang Ma − Shanghai Engineering Research Center of
Molecular Therapeutics and New Drug Development, School of
Chemistry and Molecular Engineering, East China Normal
University, Shanghai 200062, China; orcid.org/0000-0002-
7591-6748
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c00375
similar diastereoselectivity and enantioselectivities but in a very
low yield (10%, 1.2:1 dr, and 94:6/94:6 er). The significantly
reduced yield of the desired product may come from the
competing decomposition of allene under high concentrations.
As a result, using methyl alkyne as the precursor to in situ
generate allene is key for the high efficiency of this trans-
formation.
A deuterium-labeling experiment was then conducted with
deutero-alkyne d3-2a. Deuterium was incorporated into the β-,
γ-, and δ-positions of the alkylated product d3-3a (eq 2). This
Funding
This work was funded by grants from National NSF of China
(21772043), Shanghai Pujiang Program (19PJ1403000), and
the Fundamental Research Funds for the Central Universities.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Ms. Xiang Wu (East China Normal University) for
helping with the NMR analysis. We also thank Mr. Mingqi Hu
(East China Normal University) for checking the experiments.
REFERENCES
■
(1) For selected reviews, see: (a) Trost, B. M.; Van Vranken, D. L.
Chem. Rev. 1996, 96, 395−422. (b) Trost, B. M.; Crawley, M. L. Chem.
Rev. 2003, 103, 2921−2944. (c) You, S. L.; Dai, L. X. Angew. Chem., Int.
Ed. 2006, 45, 5246−5248. (d) Lu, Z.; Ma, S. Angew. Chem., Int. Ed.
2008, 47, 258−297. (e) Weaver, J. D.; Recio, A.; Grenning, A. J.;
deuterium-scrambling experiment indicates that the β-hydride
elimination step for the generation of the allene intermediate is
reversible and a π-allyl intermediate is involved in this
transformation.
̈
Tunge, J. A. Chem. Rev. 2011, 111, 1846−1913. (f) Rossler, S. L.;
Petrone, D. A.; Carreira, E. M. Acc. Chem. Res. 2019, 52, 2657−2672.
(g) Cheng, Q.; Tu, H.-F.; Zheng, C.; Qu, J.-P.; Helmchen, G.; You, S.-L.
Chem. Rev. 2019, 119, 1855−1969.
In summary, we have demonstrated a branched-selective α-
allylic alkylation of ketones with alkynes. The use of rhodium−
hydride catalysis to convert alkynes into electrophilic π-allyl
species has enabled an atom-economic protocol for the direct
access of γ,δ-unsaturated ketones from simple ketones. High
enantioselective control was achieved by utilizing a chiral
BIPHEP ligand. The development of related cooperative
catalytic systems for broader substrate scope with efficient
stereocontrol is currently underway.
(2) For selected reviews, see: (a) Hartwig, J. F.; Stanley, L. Acc. Chem.
Res. 2010, 43, 1461−1475. (b) Oliver, S.; Evans, P. A. Synthesis 2013,
45, 3179−3198. (c) Ding, C. H.; Hou, X. L. In Comprehensive Organic
Synthesis II, 2nd ed.; Knochel, P., Ed.; Elsevier: Amsterdam, 2014; Vol.
4, pp 648−698. (d) Kazmaier, U. Org. Chem. Front. 2016, 3, 1541−
̌
́
́
́
́
1560. (e) Vargova, D.; Nemethova, I.; Plevova, K.; Sebesta, R. ACS
Catal. 2019, 9, 3104−3143.
(3) For selected examples on linear and enantioselective α-allylic
alkylation of ketones via enolates, see: (a) Trost, B. M.; Schroeder, G.
M. J. Am. Chem. Soc. 1999, 121, 6759−6760. (b) You, S.-L.; Hou, X.-L.;
Dai, L.-X.; Zhu, X.-Z. Org. Lett. 2001, 3, 149−151. (c) Trost, B. M.;
Schroeder, G. M. Chem. - Eur. J. 2005, 11, 174−184. (d) Yan, X.-X.;
Liang, C.-G.; Zhang, Y.; Hong, W.; Cao, B.-X.; Dai, L.-X.; Hou, X.-L.
Angew. Chem., Int. Ed. 2005, 44, 6544−6546. (e) Yasuda, M.; Hayashi,
K.; Katoh, Y.; Shibata, I.; Baba, A. J. Am. Chem. Soc. 1998, 120, 715−
721. For selected examples on enantioselective decarboxylative α-
allylic alkylation, see: (f) Burger, E. C.; Tunge, J. A. Org. Lett. 2004, 6,
4113−4115. (g) Behenna, D. C.; Stoltz, B. M. J. Am. Chem. Soc. 2004,
126, 15044−15045. (h) Trost, B. M.; Xu, J. J. Am. Chem. Soc. 2005, 127,
17180−17181. (i) Nakamura, M.; Hajra, A.; Endo, K.; Nakamura, E.
Angew. Chem., Int. Ed. 2005, 44, 7248−7251. (j) He, H.; Zheng, X.-J.;
Li, Y.; Dai, L.-X.; You, S.-L. Org. Lett. 2007, 9, 4339−4341. (k) Trost, B.
M.; Xu, J.; Schmidt, T. J. Am. Chem. Soc. 2009, 131, 18343−18357.
(4) For selected examples on branched and enantioselective α-allylic
alkylation of ketones via enolates, see: (a) Zheng, W.-H.; Zheng, B.-H.;
Zhang, Y.; Hou, X.-L. J. Am. Chem. Soc. 2007, 129, 7718−7719.
(b) Chen, J.-P.; Ding, C.-H.; Liu, W.; Hou, X.-L.; Dai, L.-X. J. Am. Chem.
Soc. 2010, 132, 15493−15495. (c) Trost, B. M.; Malhotra, S.; Chan, W.
H. J. Am. Chem. Soc. 2011, 133, 7328−7331. (d) Chen, J.-P.; Peng, Q.;
Lei, B.-L.; Hou, X.-L.; Wu, Y.-D. J. Am. Chem. Soc. 2011, 133, 14180−
14183. (e) Yu, F.-L.; Bai, D.-C.; Liu, X.-Y.; Jiang, Y.-J.; Ding, C.-H.;
Hou, X.-L. ACS Catal. 2018, 8, 3317−3321. (f) Cheng, L.; Li, M.-M.;
Xiao, L.-J.; Xie, J.-H.; Zhou, Q.-L. J. Am. Chem. Soc. 2018, 140, 11627−
11630. (g) Graening, T.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127,
17192−17193. (h) Chen, W.; Chen, M.; Hartwig, J. F. J. Am. Chem. Soc.
2014, 136, 15825−15828. (i) Chen, M.; Hartwig, J. F. J. Am. Chem. Soc.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c00375.
Experimental procedure and spectroscopic data for all
compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Dong Xing − Shanghai Engineering Research Center of Molecular
Therapeutics and New Drug Development, School of Chemistry
and Molecular Engineering, East China Normal University,
Shanghai 200062, China; orcid.org/0000-0003-3718-
4539; Email: dxing@sat.ecnu.edu.cn
Authors
Liyu Xie − Shanghai Engineering Research Center of Molecular
Therapeutics and New Drug Development, School of Chemistry
and Molecular Engineering, East China Normal University,
Shanghai 200062, China
Haijian Yang − Shanghai Engineering Research Center of
Molecular Therapeutics and New Drug Development, School of
Chemistry and Molecular Engineering, East China Normal
University, Shanghai 200062, China
D
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pubs.acs.org/OrgLett
Letter
2015, 137, 13972−13979. (j) Liang, X.; Wei, K.; Yang, Y.-R. Chem.
Commun. 2015, 51, 17471−17474. (k) Jiang, X.; Chen, W.; Hartwig, J.
F. Angew. Chem., Int. Ed. 2016, 55, 5819−5823. (l) Kanbayashi, N.;
Yamazawa, A.; Takii, K.; Okamura, T.-a.; Onitsuka, K. Adv. Synth. Catal.
2016, 358, 555−560. (m) Cheng, L.; Li, M.-M.; Xiao, L.-J.; Xie, J.-H.;
Zhou, Q.-L. J. Am. Chem. Soc. 2018, 140, 11627−11630.
(18) The absolute configuration of 4h was assigned to be (R) by
comparison of the optical rotation with literature data.4g,8a The
stereochemistry of other acyclic ketone-derived products under the
same reaction conditions was assigned in analogy to that for 4h.
(19) For the enantioselective results of different substituted methyl
alkynes with cyclopentanone, see the Supporting Information.
(5) (a) Escher, I.; Glorius, F. Sci. Synth. 2007, 25, 733−777.
́
(b) Wright, A. E.; Botelho, J. C.; Guzman, E.; Harmody, D.; Linley, P.;
McCarthy, P. J.; Pitts, T. P.; Pomponi, S. A.; Reed, J. K. J. Nat. Prod.
2007, 70, 412−416. (c) Radin, N. S. Drug Dev. Res. 2008, 69, 15−25.
(d) Enquist, J. A., Jr; Stoltz, B. M. Nature 2008, 453, 1228−1231.
(e) Du, C.; Li, L.; Li, Y.; Xie, Z. Angew. Chem., Int. Ed. 2009, 48, 7853−
7856.
(6) For selected reviews on cooperative catalysis of transition metal
and amine, see: (a) Allen, A. E.; MacMillan, D. W. C. Chemical Science
2012, 3, 633−658. (b) Vesely, J.; Rios, R. ChemCatChem 2012, 4, 942−
953. (c) Deng, Y.; Kumar, S.; Wang, H. Chem. Commun. 2014, 50,
4272−4284. (d) Chen, D.-F.; Han, Z.-Y.; Zhou, X.-L.; Gong, L.-Z. Acc.
́
Chem. Res. 2014, 47, 2365−2377. (e) Afewerki, S.; Cordova, A. Chem.
Rev. 2016, 116, 13512−13570. (f) Kim, D.-S.; Park, W.-J.; Jun, C.-H.
Chem. Rev. 2017, 117, 8977−9015.
́
(7) For selected examples, see: (a) Ibrahem, I.; Cordova, A. Angew.
Chem., Int. Ed. 2006, 45, 1952−1956. (b) Usui, I.; Schmidt, S.; Breit, B.
Org. Lett. 2009, 11, 1453−1456. (c) Mastracchio, A.; Warkentin, A. A.;
Walji, A. M.; MacMillan, D. W. C. Proc. Natl. Acad. Sci. U. S. A. 2010,
107, 20648−20651. (d) Zhao, X.; Liu, D.; Guo, H.; Liu, Y.; Zhang, W. J.
Am. Chem. Soc. 2011, 133, 19354−19357. (e) Shibasaki, M.; Kumagai,
N.; Yasuda, S. Heterocycles 2012, 86, 745−757. (f) Huo, X.; Yang, G.;
Liu, D.; Liu, Y.; Gridnev, I. D.; Zhang, W. Angew. Chem., Int. Ed. 2014,
53, 6776−6780. (g) Butt, N.; Yang, G.; Zhang, W. Chem. Rec. 2016, 16,
2687−2696.
(8) Branched selective α-allylic alkylations of ketones were achieved
using preformed enamines as the substrates: (a) Weix, D. J.; Hartwig, J.
F. J. Am. Chem. Soc. 2007, 129, 7720−7721. (b) Liu, D.; Xie, F.; Zhang,
W. Tetrahedron Lett. 2007, 48, 7591−7594.
(9) (a) Trost, B. Science 1991, 254, 1471−1477. (b) Sheldon, R. A.
Pure Appl. Chem. 2000, 72, 1233−1246. (c) Newhouse, T.; Baran, P. S.;
Hoffmann, R. W. Chem. Soc. Rev. 2009, 38, 3010−3021.
(10) For selected reviews, see: (a) Koschker, P.; Breit, B. Acc. Chem.
Res. 2016, 49, 1524−1536. (b) Haydl, A. M.; Breit, B.; Liang, T.;
Krische, M. J. Angew. Chem., Int. Ed. 2017, 56, 11312−11325. (c) Wang,
P.-S.; Shen, M.-L.; Gong, L.-Z. Synthesis 2018, 50, 956−967.
(11) (a) Trost, B. M.; Schmidt, T. J. Am. Chem. Soc. 1988, 110, 2301−
2303. (b) Trost, B. M.; Brieden, W.; Baringhaus, K. H. Angew. Chem.,
Int. Ed. Engl. 1992, 31, 1335−1336.
(12) (a) Kadota, I.; Shibuya, A.; Gyoung, Y. S.; Yamamoto, Y.
Palladium/Acetic Acid Catalyzed Allylation of Some Pronucleophiles
with Simple Alkynes. J. Am. Chem. Soc. 1998, 120, 10262−10263.
(b) Patil, N. T.; Yamamoto, Y. J. Org. Chem. 2004, 69, 6478−6481.
(c) Patil, N. T.; Kadota, I.; Shibuya, A.; Gyoung, Y. S.; Yamamoto, Y.
Adv. Synth. Catal. 2004, 346, 800−804. (d) Patil, N. T.; Song, D.;
Yamamoto, Y. Eur. J. Org. Chem. 2006, 2006, 4211−4213.
(13) (a) Beck, T. M.; Breit, B. Org. Lett. 2016, 18, 124−127. (b) Beck,
T. M.; Breit, B. Eur. J. Org. Chem. 2016, 2016, 5839−5844. (c) Li, C.;
Grugel, C. P.; Breit, B. Chem. Commun. 2016, 52, 5840−5843.
(d) Zheng, J.; Breit, B. Org. Lett. 2018, 20, 1866−1870.
(14) (a) Cruz, F. A.; Chen, Z.; Kurtoic, S. I.; Dong, V. M. Chem.
Commun. 2016, 52, 5836−5839. (b) Cruz, F. A.; Dong, V. M. J. Am.
Chem. Soc. 2017, 139, 1029−1032.
(15) (a) Onodera, G.; Kato, M.; Kawano, R.; Kometani, Y.; Takeuchi,
R. Org. Lett. 2009, 11, 5038−5041. (b) Yang, C.; Zhang, K.; Wu, Z.;
Yao, H.; Lin, A. Org. Lett. 2016, 18, 5332−5335. (c) Gao, S.; Liu, H.;
Wu, Z.; Yao, H.; Lin, A. Green Chem. 2017, 19, 1861−1865. (d) Lee, J.
T. D.; Zhao, Y. Chem. - Eur. J. 2018, 24, 9520−9524. (e) Ren, W.; Zuo,
Q.-M.; Niu, Y.-N.; Yang, S.-D. Org. Lett. 2019, 21, 7956−7960.
(16) For detailed condition optimizations for the reaction between
acetophenone 1h and alkyne 2a, see the Supporting Information.
(17) For details, see the Supporting Information.
E
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