Full text of DOI:10.1021/acscatal.7b04313

Letter
pubs.acs.org/acscatalysis
Cite This: ACS Catal. 2018, 8, 3317−3321
Pd-Catalyzed Allylic Alkylation of gem-Alkyl,Aryl-Disubstituted Allyl
Reagents with Ketones: Diastereoselective Construction of Vicinal
Tertiary and Quaternary Carbon Centers
Fei-Le Yu,¶,† Da-Chang Bai,¶,†,‡ Xiu-Yan Liu,¶,† Yang-Jie Jiang,†,∥ Chang-Hua Ding,*,†
and Xue-Long Hou*,†,§
†State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
‡School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan Province 453007, China
§Shanghai−Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, China
∥University of Chinese Academy of Sciences, Beijing 100049, China
S
* Supporting Information
ABSTRACT: (E)-gem-Alkyl,aryl-disubstituted allyl carbonates
can react with ketones under Pd catalysis using a commercially
available NHC ligand by suppressing the β-H elimination.
Ketones with α-tertiary, β-quaternary carbon stereocenters
were produced in high yields with high regio- and
diastereoselectivities. Kinetic resolution of the reaction product
via CBS reduction afforded the optically active ketone as well
as the alcohol with high enantioselectivity (S-factor = 35). The
utility of the methodology was also demonstrated by
transformations of the reaction products.
KEYWORDS: palladium catalysis, allylic alkylation, regioselectivity, diastereoselectivity, vicinal tertiary and quaternary stereocenters
alladium-catalyzed allylic alkylation reactions (Pd-catalyzed
AA), an important protocol in organic synthesis, have
Scheme 1. Different Modes for the Construction of Carbon
Stereocenters in Ketones
P
attracted great attention since their discovery approximately 50
years ago.1 Currently, unstabilized carbanions can be used as
the nucleophile,2−4 and two vicinal carbon stereocenters can be
formed.2c,4c,f,i,5 Ketones with vicinal carbon stereocenters are an
important subunit in organic synthesis.6 Several strategies have
been developed to use ketones as nucleophiles in Pd-catalyzed
AA,2,4b,c,f,i and two carbon stereocenters can be installed in the
products.2c,4c,f,i However, only vicinal tertiary/tertiary carbon
centers could be established. The formation of vicinal tertiary/
quaternary carbon stereocenters in ketones have not been
reported; however, methods of installing quaternary carbon
centers at the α-position of ketones are known (Scheme
1).2b,f,g,4b,7,8 Furthermore, 1,1-disubstituted allyl reagents have
to be used to construct quaternary carbon stereocenters at the
β-position of ketones,7 which should be more challenging in
Pd-catalyzed AA reactions. A method for generating ketones
bearing vicinal tertiary and quaternary carbon stereocenters via
Pd-catalyzed AA reactions remains to be explored.
commercially available N-heterocyclic carbene (NHC) as the
ligand in the Pd-catalyzed AA of acyclic ketones with
monosubstituted allyl reagents.4i As this is a simple and a
facile way to control the regioselectivity in the Pd-catalyzed AA,
further investigations have been conducted to determine the
We have achieved regiocontrol in Pd-catalyzed AA reactions
of monosubstituted allyl reagents with different nucleophiles,4
which generates the quaternary carbon in the allyl fragment,9b
and the method can generate vicinal carbon stereocenters in
ketones and carboxylic acid derivatives.4c,e Recently, we found
that regioselectivity could also be controlled by simply using a
Received: December 18, 2017
Revised: March 8, 2018
© XXXX American Chemical Society
3317
DOI: 10.1021/acscatal.7b04313
ACS Catal. 2018, 8, 3317−3321

ACS Catalysis
Letter
utility of this strategy. In this Letter, we report our new finding
that 1-alkyl-1-aryl disubstituted allyl reagents can be success-
fully used in Pd-catalyzed AA reactions by suppressing the β-H
elimination based upon the understanding of β-H elimination
mechanisms and afford ketones with α-tertiary-β-quaternary
carbon stereocenters in high yields with excellent regio- and
diastereoselectivities (Scheme 1). Optically active allylic
alkylated products were obtained by kinetic resolution.
observed when (E)-tert-butyl (3-phenylbut-2-en-al)carbonate
(2a) was reacted with ketone 1a under the above reaction
conditions (Table 1, entry 1).
Table 1. Influence of the Reaction Parameters on the Pd-
Catalyzed Reaction of Cyclohexanone (1a) with Allyl
a
Substrate (E)-2a
Pd/NHC-catalyzed AAs of ketones with monosubstituted
allyl reagents proceeds via the oxygen of the ketone enolate
attacking the palladium of the Pd-π-allyl complex followed by a
[3,3′]-reductive elimination.4i We reasoned that a quaternary
carbon stereocenter could be installed using terminal
disubstituted allyl compounds through this process because
the two substituents should be far from the Pd in the transition
state the steric hindrance between the allyl reagent and the
nucleophile should be avoided.
To test this idea, the reaction of (Z)-tert-butyl (3-phenylbut-
2-en-al)carbonate (2a) with cyclohexanone (1a) as the
nucleophile in the presence of [Pd(η3-C3H5)Cl]2 and an
imidazolium salt (IPr·HCl (L1)) was tested. However, only a
trace amount of allylated product 3a was observed, and diene 4
was detected as the major component and was generated
through the β-H elimination of allyl (Z)-2a (eq 1) in 72% yield.
3a+5a
b
3a anti/
2a
4
c
c
b
b
entry
L
solvent
(%)
3a/5a
syn
(%)
(%)
de
f
,
1
2
3
4
5
6
7
8
9
L1
L1
L1
L1
L2
L3
L4
L5
L5
L5
L5
L5
L5
L5
L5
L5
THF
49
69
69
78
12
27
25
81
90
88
78
67
81
95
86
86
96/4
95/5
93/7
95/5
84/16
93/7
26
15
6
-
d
THF
-
-
dg
,
THF
89/11
87/13
-
THF
0
7
THF
0/100
47/53
60/40
91/9
61
33
43
0
16
40
28
10
-
THF
45/55
70/30
91/9
THF
THF
hexane
toluene
Et2O
63/37
60/40
54/46
63/37
92/8
53/47
71/29
82/18
87/13
91/9
0
10
11
12
13
14
15
0
-
0
-
DME
dioxane
dioxane
dioxane
dioxane
0
-
0
-
h
i
90/10
96/4
86/14
98/2
0
3
β-H Elimination reactions are a general process in transition-
metal chemistry and might be one of the major reasons that
prevent the use of alkyl-substituted allyl reagents in Pd-
catalyzed AA reactions. Three mechanisms have been proposed
for the β-H elimination reactions (Scheme 2a−c).10 Because
0
0
ij
16 ,
96/4
98/2
0
0
a
Reaction conditions: 1a/LDA/(E)-2a/[Pd(η3-C3H5)Cl]2/Ligand =
b
200/200/100/2.5/5; 0.1 M of (E)-2a. Yield determined by 1H NMR
c
using mesitylene as an internal reference. Determined by 1H NMR of
d
e
the crude product. 1a/LDA/(E)-2a = 150/150/100. Reaction
performed at rt. Not determined. Conducted at reflux. 1a/LDA/
(E)-2a/Pd(OAc)2/S-IPr·HBF4 = 200/200/100/5/5. 1a/LDA/(E)-
f
g
h
Scheme 2. Reported Mechanisms for β-H Elimination
Processes
i
2a/Pd(OAc)2/S-IPr·HBF4 = 150/150/100/5/5; reaction time: 12 h.
j
Reaction time: 22 h.
To improve the efficiency of the reaction, the reaction
conditions were optimized by varying the reaction parameters
(Table 1). Both the yield and the dr increased significantly (to
69% and 93/7, respectively) when the reaction temperature was
elevated to 50 °C (entry 2), and similar results were obtained
when the reaction was conducted in refluxing THF (entry 3). A
further increase in the yield to 78% was realized by changing
the ratio of 1a/2a from 1.5/1 to 2.0/1; however, the
diastereoselectivity of 3a decreased to 83/17, and β-H
elimination product 4 was observed (entry 4 vs entry 2). It
was found that the structure of the NHC ligand substantially
influenced the efficiency of this reaction. A very low yield of
linear product 5a was obtained using the 1,3-diphenyl NHC
derived from L2 (entry 5), while a lower diastereoselectivity
accompanied by some diene 4 were afforded if N,N’-bis-2,4,6-
trimethyl phenyl-substituted NHC L3 and bulkier aryl
substituted L4 were the ligands (entries 6 and 7). However, a
high yield of 3a with high regio- and diastereoselectivities was
obtained by using S-IPr·HCl L5, an NHC ligand with an
imidazoline ring, and the yield of the desired product was 81%
our reaction proceeded under basic conditions, the β-H
elimination reaction might occur from structure (d) via
mechanism c, which would give anti-elimination (Scheme 2),
and form 4 from (Z)-2a. If this were the case, this β-H
elimination process should be suppressed by the use of (E)-tert-
butyl (3-phenylbut-2-en-al)carbonate (2a) instead because (e)
would be formed instead of (d). Desired branched product 3a
with vicinal tertiary and quaternary carbon centers and linear
allylation product 5a were obtained in 49% yield (branched/
linear (B/L) ratio being 96/4 and dr being 84/16) along with
the recovery of 26% of 2a, and the β-H elimination process was
efficiently suppressed. No β-H elimination product 4 was
3318
DOI: 10.1021/acscatal.7b04313
ACS Catal. 2018, 8, 3317−3321

ACS Catalysis
Letter
with a B/L ratio of 91/9 and a dr of 91/9 (entry 8 vs entry 4).
The studies on the influence of solvent on the reaction showed
that nonpolar solvents such as n-hexane and toluene delivered
poor regio- and diastereoselectivities (entries 9 and 10), and
Et2O and DME gave lower regioselectivity (entries 11 and 12),
while 1,4-dioxane provided the same yield and selectivities as
THF (entry 13 vs entry 8).
Table 2. Substrate Scope of the Pd-Catalyzed Reaction of
Cyclic Ketones 1 with 1,1-Disubstituted Allyl Substrates 2
a
Because Cl− ions will accelerate the π−σ−π process of the
Pd-π-allyl complex11 even though the interconversion between
intermediates d and e should occur via this process,1 we
deduced that the efficiency of the reaction may be improved by
using (E)-allyl reagents if the reaction proceeds in the absence
of Cl− ion; thus, this will reduce the rate of the π−σ−π process
and reduce the amount of intermediate (d) formed (Scheme
2). Furthermore, alkyl-substituted allyl reagents, challenging
substrates for Pd-catalyzed AA reactions, could be used if the β-
H elimination process is suppressed under Cl− ion-free
conditions.
With this idea in mind, further investigations were conducted
by changing the Pd species and the counterions of L5. It was
found that the combination of Pd(OAc)2 with S-IPr·HBF4 and
t-BuOK was the optimal choice. The allylated products were
obtained in 95% yield with a 90/10 B/L and an 86/14 dr, and
the yield of diene 4 was 3% (entry 14 vs entry 8, Table 1). By
changing the mol ratio of 1a/LDA/(E)-2a from 200/200/100
to 150/150/100, the yield decreased from 95% to 86%, but the
B/L ratio (96/4) and the dr (98/2) of 3a were improved
significantly (entry 15 vs entry 14, Table 1). In addition,
extending the reaction time from 12 to 22 h did not affect the
yield or regio- and diastereoselectivities of the reaction (entry
16 vs entry 15, Table 1). To our delight, excellent results were
obtained when (E)-ethyl,phenyl-substituted allyl 2b was used.
The yield of product 3b was 91% with a B/L ratio of 96/4 and
a dr of 99/1 (Table 2).
a
Reaction conditions: 1/LiHMDS/2/Pd(OAc)2/S-IPr·HBF4 = 150/
1
150/100/5.0/5.0; B/L and dr was determined by H NMR; isolated
yield. Reaction with cyclohexanone (1a). Reaction with (E)-2a.
b
c
Under these reaction conditions, the scope of the Pd-
catalyzed reaction of cyclic ketones 1 with (E)-1-alkyl-1-aryl-
disubstituted allyl substrates 2 was investigated. As shown in
Table 2, various alkyl substituent-containing allyl reagents 2
and cyclic ketones with rings of various sizes were suitable for
the reaction and provided corresponding products 3a−o with
vicinal tertiary and quaternary carbon stereocenters in high
yields with excellent regio- and diastereoselectivities (B/L: 90/
10−96/4 and dr: ≥ 98/2−89/11). The allyl substrates 2 with
an aryl ring having either electron-donating or electron-
withdrawing substituents (Me, OMe and CF3) at the p- or
m-positions reacted smoothly with ketone 1a to efficiently
afford allylated products 3g−j. 2-Furyl-substituted allyl
substrate 2k was also an excellent electrophile and afforded
corresponding product 3k. It was noted that when the alkyl
substituent of allyl 2 became bulkier, the reaction yield
decreased due to lower conversion (3e vs 3f). The reaction
was fully suppressed if iso-propyl or ortho-methyl phenyl-
substituted allyls 2 were used as the electrophiles (2l and 2m).
Additionally, the reaction of tert-butyl (3-methylbut-2-en-1-yl)
carbonate with 1-tetralone afforded isoprene derived from the
β-H elimination accompanied by a trace amount of allylated
products (for details, see Supporting Information). In addition
to cyclohexanone (1a), cycloheptanone, cyclooctanone, 1-
tetralone, and 1-benzosuberone were competent nucleophiles
for this reaction to lead the desired allylated products (3l−o) in
high yields with excellent stereoselectivities. No reaction
occurred when cyclopentanone was used as the substrate.
Acyclic ketones such as 1-phenylbutan-1-one and pentan-3-one
were also not well-tolerated in this allylic alkylation reaction as
they afforded the corresponding allylated products in very low
yields with low regio- and diastereoselectivities (3p and 3q).
The reaction of allyl 2a with cyclohexanone (1a) was also
studied using chiral NHCs. Unfortunately, the enantioselectiv-
ity was not satisfactory, and only 16% ee was obtained for
product 3a (for details, see SI). However, 44% yield of optically
active 3a (61% ee) and 40% yield of reduced product 6 (90%
ee) were obtained by kinetic resolution of allylation product 3a
via CBS reduction (S-factor = 35, eq 2),12 which provides an
alternative approach to preparing optically active 3. The
absolute configuration of (+)-3a was determined to be (R,R)
(see SI).
Some transformations of product 3a were carried out (eq 3).
Allylated product 3a was diastereoselectively reduced by L-
3319
DOI: 10.1021/acscatal.7b04313
ACS Catal. 2018, 8, 3317−3321

ACS Catalysis
Letter
allyl metal complexes. In Comprehensive Organic Synthesis, 2nd ed., Vol.
4; Molander, G. A., Knochel, P., Eds; Elsevier: Oxford, 2014; pp 648−
698.
selectride to give alcohol 6 in 92% yield, which was then
cyclized in the presence of NBS to furnish product 7 with a
fully substituted tetrahydrofuran ring in 79% yield. Dihydrox-
ylation/periodate cleavage of 3a followed by reduction and
reductive amination gave bicyclic pyrrolidine 8 in 63% overall
yield.
The reaction can also be conducted on a gram scale. The
reaction of allyl 2a (1.25 g) with cyclohexanone (0.75 g)
proceeded smoothly with 2.5 mol % Pd(OAc)2 and S-IPr·
HBF4 as the catalyst to produce 0.98 g of product 3a in 86%
yield with 97/3 B/L and 96/4 dr.
The present work demonstrates that β-H elimination could
be suppressed by changing the configuration of the allyl
substrates, and alkyl-substituted allyl reagents could then be
successfully applied in Pd-catalyzed AA reactions. Vicinal
tertiary and quaternary stereocenters in ketones were
established in excellent regio- and diastereoselectivities by a
simple and efficient method using a commercially available
NHC ligand. The utility of this protocol has been demonstrated
by the conversion as well as the kinetic resolution of the allylic
alkylation products. This study offers a new platform for Pd-
catalyzed AA reactions. Further investigations on an asym-
metric variant along with other aspects of the aforementioned
methodology are in progress.
(2) Some examples using ketones in Pd-catalyzed AA reaction:
(a) Trost, B. M.; Self, C. R. On the palladium-catalyzed alkylation of
silyl-substituted allyl acetates with enolates. J. Org. Chem. 1984, 49,
468−473. (b) Trost, B. M.; Schroeder, G. M. Palladium-catalyzed
asymmetric alkylation of ketone enolates. J. Am. Chem. Soc. 1999, 121,
6759−6760. (c) Braun, M.; Laicher, F.; Meier, T. Diastereoselective
and enantioselective palladium-catalyzed allylic substitution with
nonstabilized ketone enolates. Angew. Chem., Int. Ed. 2000, 39,
3494−3497. (d) Burger, E. C.; Tunge, J. A. Asymmetric allylic
alkylation of ketone enolates: an asymmetric Claisen surrogate. Org.
Lett. 2004, 6, 4113−4115. (e) Behenna, C.; Stoltz, B. M. The
enantioselective Tsuji allylation. J. Am. Chem. Soc. 2004, 126, 15044−
15045. (f) Trost, B. M.; Xu, J. Palladium-catalyzed asymmetric allylic
α-alkylation of acyclic ketones. J. Am. Chem. Soc. 2005, 127, 17180−
́
́
17181. (g) Belanger, E.; Cantin, K.; Messe, O.; Tremblay, M.; Paquin,
J.-F. Enantioselective Pd-catalyzed allylation reaction of fluorinated
silyl enol ethers. J. Am. Chem. Soc. 2007, 129, 1034−1035. (h) Zhao,
X.; Liu, D.; Guo, H.; Liu, Y.; Zhang, W. C−N bond cleavage of allylic
amines via hydrogen bond activation with alcohol solvents in Pd-
catalyzed allylic alkylation of carbonyl compounds. J. Am. Chem. Soc.
2011, 133, 19354−19357.
(3) Some examples using other unstabilized carbanions: (a) Weiß, T.
D.; Helmchen, G.; Kazmaier, U. Synthesis of amino acid derivatives via
enantio- and diastereoselective Pd-catalyzed allylic substitutions with a
non-stabilized enolate as nucleophile. Chem. Commun. 2002, 1270−
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acscatal.7b04313.
■
́
1271. (b) Ibrahem, I.; Cordova, A. Direct catalytic intermolecular α-
S
allylic alkylation of aldehydes by combination of transition-metal and
organocatalysis. Angew. Chem., Int. Ed. 2006, 45, 1952−1956.
(c) Trost, B. M.; Thaisrivongs, D. A. Palladium-catalyzed regio-,
diastereo-, and enantioselective benzylic allylation of 2-substituted
pyridines. J. Am. Chem. Soc. 2009, 131, 12056−12057. (d) Sha, S. C.;
Zhang, J.; Carroll, P. J.; Walsh, P. J. Raising the pKa limit of “soft”
nucleophiles in palladium-catalyzed allylic substitutions: application of
diarylmethane pronucleophiles. J. Am. Chem. Soc. 2013, 135, 17602−
17609. (e) Tao, Z. L.; Zhang, W. Q.; Chen, D. F.; Adele, A.; Gong, L.
Z. Pd-catalyzed asymmetric allylic alkylation of pyrazol-5-ones with
allylic alcohols: the role of the chiral phosphoric acid in C−O bond
cleavage and stereocontrol. J. Am. Chem. Soc. 2013, 135, 9255−9258.
(f) Mao, J.; Zhang, J.; Jiang, H.; Bellomo, A.; Zhang, M.; Gao, Z.;
Dreher, S. D.; Walsh, P. J. Palladium-catalyzed asymmetric allylic
alkylations with toluene derivatives as pronucleophiles. Angew. Chem.,
Int. Ed. 2016, 55, 2526−2530.
X-ray data of ( )-3a (CIF)
X-ray data of 9 (CIF)
Optimization data, experimental procedures, NMR and
HPLC spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: xlhou@sioc.ac.cn.
*E-mail: dingch@sioc.ac.cn.
ORCID
Da-Chang Bai: 0000-0001-7342-2966
Xue-Long Hou: 0000-0003-4396-3184
(4) (a) You, S.-L.; Hou, X.-L.; Dai, L.-X.; Zhu, X.-Z. Highly efficient
ligands for palladium-catalyzed asymmetric alkylation of ketone
enolates. Org. Lett. 2001, 3, 149−151. (b) Yan, X. X.; Liang, C. G.;
Zhang, Y.; Hong, W.; Cao, B. X.; Dai, L. X.; Hou, X. L. Highly
enantioselective Pd-catalyzed allylic alkylations of acyclic ketones.
Angew. Chem., Int. Ed. 2005, 44, 6544−6546. (c) Zheng, W.-H.; Zheng,
B.-H.; Zhang, Y.; Hou, X.-L. Highly regio-, diastereo-, and
enantioselective Pd-catalyzed allylic alkylation of acyclic ketone
enolates with monosubstituted allyl substrates. J. Am. Chem. Soc.
2007, 129, 7718−7719. (d) Zhang, K.; Peng, Q.; Hou, X.-L.; Wu, Y.
D. Highly enantioselective palladium-catalyzed alkylation of acyclic
amides. Angew. Chem., Int. Ed. 2008, 47, 1741−1744. (e) Chen, J.-P.;
Ding, C.-H.; Liu, W.; Hou, X.-L.; Dai, L.-X. Palladium-catalyzed regio-,
diastereo-, and enantioselective allylic alkylation of acylsilanes with
monosubstituted allyl substrates. J. Am. Chem. Soc. 2010, 132, 15493−
15495. (f) Chen, J.-P.; Peng, Q.; Lei, B.-L.; Hou, X.-L.; Wu, Y.-D.
Chemo- and regioselectivity-tunable Pd-catalyzed allylic alkylation of
imines. J. Am. Chem. Soc. 2011, 133, 14180−14183. (g) Chen, T. G.;
Fang, P.; Dai, L. X.; Hou, L. H. Palladium-catalyzed asymmetric allylic
alkylation reaction of 2-mono-substituted indolin-3-ones. Synthesis
2015, 47, 134−140. (h) Li, X. H.; Wan, S. L.; Chen, D.; Liu, Q. R.;
Ding, C. H.; Fang, P.; Hou, X. L. Enantioselective construction of
quaternary carbon stereocenter via palladium-catalyzed asymmetric
allylic alkylation of lactones. Synthesis 2016, 48, 1568−1572. (i) Bai,
Author Contributions
¶(F.-L.Y., D.-C.B., X.-Y.L.) These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support was received from the National Natural
Science Foundation of China (NSFC) (21532010, 21472214,
21772215, and 21421091), the Strategic Priority Research
Program of the Chinese Academy of Sciences (XDB20030100),
the Chinese Academy of Sciences, the Technology Commission
of Shanghai Municipality, and the Croucher Foundation of
Hong Kong.
REFERENCES
■
(1) (a) Pfaltz, A.; Lautens, M. Allylic substitution reactions. In
Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer- Verlag: Berlin, 1999; Vol. 2, p 833−
886. (b) Trost, B. M.; Crawley, M. L. Asymmetric transition-metal-
catalyzed allylic alkylations: applications in total synthesis. Chem. Rev.
2003, 103, 2921−2943. (c) Ding, C.-H.; Hou, X.-L. Nucleophiles with
3320
DOI: 10.1021/acscatal.7b04313
ACS Catal. 2018, 8, 3317−3321

ACS Catalysis
Letter
D.-C.; Yu, F.-L.; Wang, W.-Y.; Chen, D.; Li, H.; Liu, Q.-R.; Ding, C.-
H.; Chen, B.; Hou, X.-L. Palladium/N-heterocyclic carbene catalysed
regio and diastereoselective reaction of ketones with allyl reagents via
inner-sphere mechanism. Nat. Commun. 2016, 7, 11806−11817.
(5) For some examples: (a) Kazmaier, U.; Zumpe, F. L. Chelated
enolates of amino acid estersefficient nucleophiles in palladium-
catalyzed allylic substitutions. Angew. Chem., Int. Ed. 1999, 38, 1468−
1470. (b) Nakoji, M.; Kanayama, T.; Okino, T.; Takemoto, Y. Pd-
catalyzed asymmetric allylic alkylation of glycine imino ester using a
chiral phase-transfer catalyst. J. Org. Chem. 2002, 67, 7418−7423.
(c) Du, C.; Li, L.; Li, Y.; Xie, Z. Construction of two vicinal quaternary
carbons by asymmetric allylic alkylation: total synthesis of hyper-
olactone C and (−)-biyouyanagin A. Angew. Chem., Int. Ed. 2009, 48,
7853−7856. (d) Lin, H.-C.; Wang, P.-S.; Tao, Z.-L.; Chen, Y.-G.; Han,
Z.-Y.; Gong, L.-Z. Highly enantioselective allylic C−H alkylation of
terminal olefins with pyrazol-5-ones enabled by cooperative catalysis of
palladium complex and Brønsted acid. J. Am. Chem. Soc. 2016, 138,
14354−14361. (g) Su, Y.-L.; Han, Z.-Y.; Li, Y.-H.; Gong, L.-Z.
Asymmetric allylation of furfural derivatives: synergistic effect of chiral
ligand and organocatalyst on stereochemical control. ACS Catal. 2017,
7, 7917−7922. (h) Huo, X.; He, R.; Fu, J.; Zhang, J.; Yang, G.; Zhang,
W. Stereoselective and site-specific allylic alkylation of amino acids and
small peptides via a Pd/Cu dual catalysis. J. Am. Chem. Soc. 2017, 139,
9819−9822.
(9) (a) Krafft, M. E.; Sugiura, M.; Abboud, K. A. Novel use of ring
strain to control regioselectivity: alkene-directed, palladium-catalyzed
allylation. J. Am. Chem. Soc. 2001, 123, 9174−9175. (b) Hou, X.-L.;
Sun, N. Construction of chiral quaternary carbon eenters by Pd-
catalyzed asymmetric allylic substitution with P,N-1,1’-ferrocene
ligands. Org. Lett. 2004, 6, 4399−4401. (c) Johns, A. M.; Liu, Z.;
Hartwig, J. F. Primary tert- and sec-allylamines via palladium-catalyzed
hydroamination and allylic substitution with hydrazine and hydroxyl-
amine derivatives. Angew. Chem., Int. Ed. 2007, 46, 7259−7261.
(d) Trost, B. M.; Malhotra, S.; Chan, W. H. Exercising regiocontrol in
palladium-catalyzed asymmetric prenylations and geranylation: unify-
ing strategy toward flustramines A and B. J. Am. Chem. Soc. 2011, 133,
7328−7331. (e) Zhang, P.; Le, H.; Kyne, R. E.; Morken, J. P.
Enantioselective construction of all-carbon quaternary centers by
branch-selective Pd-catalyzed allyl−allyl cross-coupling. J. Am. Chem.
Soc. 2011, 133, 9716−9719. (f) Ardolino, M. J.; Morken, J. P.
Congested C−C bonds by Pd-catalyzed enantioselective allyl−allyl
cross-coupling, a mechanism-guided solution. J. Am. Chem. Soc. 2014,
136, 7092−7100.
(10) (a) Smutny, E. J. Oligomerization and dimerization of butadiene
under homogeneous catalysis. Reaction with nucleophiles and the
synthesis of 1,3,7-octatriene. J. Am. Chem. Soc. 1967, 89, 6793−6794.
(b) Takashi, T.; Naoshi, N.; Tooru, M.; Hisao, Y.; Jiro, T. Palladium
catalyzed selective formation of homogannular conjugated dienes from
allylic esters in decalin derivatives. And its application to the synthesis
of 1-α-hydroxy-provitamin D3. Tetrahedron Lett. 1990, 31, 4333−
4336. (c) Keinan, E.; Kumar, S.; Dangur, V.; Vaya, J. Evidence for a
cyclic mechanism in (η3-Allyl)palladium chemistry. Promotion of β-
hydride elimination by unsaturated organometallics. J. Am. Chem. Soc.
1994, 116, 11151−11152. (d) Andersson, P. G.; Schab, S. Mechanism
of the palladium-catalyzed elimination of acetic acid from allylic
acetates. Organometallics 1995, 14, 1−2.
(6) (a) Ortega, A.; Blount, J. F.; Manchand, P. S. Salvinorin, a new
trans-neoclerodane diterpene from Salvia divinorum (Labiatae). J.
Chem. Soc., Perkin Trans. 1 1982, 1, 2505−2508. (b) Wang, Z.-W.;
Wang, J.-S.; Luo, J.; Kong, L.-Y. α-Glucosidase inhibitory triterpenoids
from the stem barks of Uncaria laevigata. Fitoterapia 2013, 90, 30−37.
́
(c) Cen-Pacheco, F.; Martín, M. N.; Fernandez, J. J.; Daranas, A. H.
New oxidized zoanthamines from a Canary islands zoanthus sp. Mar.
Drugs 2014, 12, 5188−5196. (d) Feng, J. J.; Holmes, M.; Krische, M. J.
Acyclic quaternary carbon stereocenters via enantioselective transition
metal catalysis. Chem. Rev. 2017, 117, 12564−12580.
(11) (a) Sjogren, M. P. T.; Hansson, S.; Åakermark, B.; Vitagliano, A.
Stereo- and regiocontrol in palladium-catalyzed allylic alkylation using
1,10-phenanthrolines as ligands. Organometallics 1994, 13, 1963−1971.
(b) Trost, B. M.; Toste, F. D. Regio- and enantioselective allylic
alkylation of an unsymmetrical substrate: A working model. J. Am.
Chem. Soc. 1999, 121, 4545−4554.
(12) (a) Corey, E. J.; Shibata, S.; Bakshi, R. K. An efficient and
catalytically enantioselective route to (S)-(−)-phenyloxirane. J. Org.
Chem. 1988, 53, 2861−2863. (b) Tarr, J. C.; Johnson, J. S. Lanthanum
tricyanide-catalyzed acyl silane−ketone benzoin additions and kinetic
resolution of resultant α-silyloxyketones. J. Org. Chem. 2010, 75,
3317−3325.
(7) Examples for using β-keto esters in Pd-catalyzed AA reaction to
install α-quaternary-β-tertiary stereo centers: (a) Trost, B. M.;
Radinov, R.; Grenzer, E. M. Asymmetric alkylation of β-ketoesters. J.
Am. Chem. Soc. 1997, 119, 7879−7880. (b) Trost, B. M.; Jiang, C. Pd-
catalyzed asymmetric allylic alkylation. a short route to the cyclopentyl
core of viridenomycin. Org. Lett. 2003, 5, 1563−1565. (c) Liu, J.; Han,
Z.; Wang, X.; Meng, F.; Wang, Z.; Ding, K. Palladium-catalyzed
asymmetric construction of vicinal tertiary and all-carbon quaternary
stereocenters by allylation of β-ketocarbonyls with Morita−Baylis−
Hillman adducts. Angew. Chem., Int. Ed. 2017, 56, 5050−5054.
(8) Examples for preparation of ketones bearing α-quaternary-β-
tertiary stereo centers via other transition-metal-catalyzed AA reaction:
Mo: (a) Trost, B. M.; Dogra, K. Synthesis of novel quaternary amino
acids using molybdenum-catalyzed asymmetric allylic alkylation. J. Am.
Chem. Soc. 2002, 124, 7256−7257. (b) Trost, B. M.; Miller, J. R.;
Hoffman, C. M., Jr. A highly enantio- and diastereoselective
molybdenum-catalyzed asymmetric allylic alkylation of cyanoesters. J.
Am. Chem. Soc. 2011, 133, 8165−8167 Ir. (c) Krautwald, S.; Sarlah, D.;
Schafroth, M. A.; Carreira, E. M. Enantio- and diastereodivergent dual
Catalysis: α-allylation of branched aldehydes. Science 2013, 340, 1065−
1068. (d) Liu, W. B.; Reeves, C. M.; Virgil, S. C.; Stoltz, B. M.
Construction of vicinal tertiary and all-Carbon quaternary stereo-
centers via Ir-catalyzed regio-, diastereo-, and enantioselective allylic
alkylation and applications in sequential Pd catalysis. J. Am. Chem. Soc.
2013, 135, 10626−10629. (e) Chen, W. Y.; Hartwig, J. F. Cation
control of diastereoselectivity in Iridium-catalyzed allylic substitutions.
formation of enantioenriched tertiary alcohols and thioethers by
allylation of 5H-oxazol-4-ones and 5H-thiazol-4-ones. J. Am. Chem. Soc.
2014, 136, 377−382. (f) Jiang, X. Y.; Chen, W. Y.; Hartwig, J. F.
Iridium-catalyzed diastereoselective and enantioselective allylic sub-
stitutions with acyclic α-alkoxy ketones. Angew. Chem., Int. Ed. 2016,
55, 5819−5823. (g) He, R.; Liu, P.; Huo, X.; Zhang, W. Ir/Zn dual
catalysis: enantioselective and diastereodivergent α-allylation of
unprotected α-hydroxy indanones. Org. Lett. 2017, 19, 5513−5516.
3321
DOI: 10.1021/acscatal.7b04313
ACS Catal. 2018, 8, 3317−3321