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\begin{document}

\title{Pd-Catalyzed Asymmetric Allylic C-H Functionalization}



\author[1]{Pu-Sheng  Wang}%
\author[1]{Liuzhu' Gong}%
\affil[1]{University of Science and Technology of China}%


\vspace{-1em}



  
  \date{June 14, 2024}


\begingroup
\let\center\flushleft
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\maketitle
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\selectlanguage{english}
\begin{abstract}
Pd-catalyzed asymmetric allylic C-H functionalization has emerged as a
powerful tool to access chiral, densely functionalized molecules from
easily ac-cessible alkenes, enabling the increase of the step- or
atom-economy by minimizing functional group manipulations for preparing
allylating reagents. Due to the inadequacy of stereoselection
strategies, the asymmetric allylic C-H functionalization is still in the
early stage. In this essay, we will describe our journey to
identification of asymmetric catalytic systems, mechanism of allylic C-H
activation, control of stereo- and regioselectivity, and applica-tions
in asymmetric synthesis.%
\end{abstract}%



\sloppy


\textbf{Cite this paper:}\emph{Chin. J. Chem.} \textbf{2023} , \emph{41}
, XXX---XXX. \textbf{DOI: 10.1002/cjoc.202300XXX}

Pd-Catalyzed Asymmetric Allylic C-H Functionalization

Pu-Sheng Wang,\emph{\textsuperscript{a}} and Liu-Zhu
Gong*\textsuperscript{,\emph{a,b}}

\textsuperscript{a} Department of Chemistry, University of Science and
Technology of China, Hefei 230026, China\textsuperscript{b} Center for
Excellence in Molecular Synthesis of CAS, University of Science and
Technology of China, Hefei 230026, China\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\emph{Interview} \textbf{Question 1?} Answer 1. Interview Question 2?
Answer 2. Interview Question 3? Answer 3. & Interview Question 4? Answer
4. Interview Question 5? Answer 5. Interview Question 6? Answer
6.\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{longtable}[]{@{}l@{}}
\toprule
\textbf{Comprehensive Summary}\tabularnewline
\midrule
\endhead
Pd-catalyzed asymmetric allylic C-H functionalization has emerged as a
powerful tool to access chiral, densely functionalized molecules from
easily accessible alkenes, enabling the increase of the step- or
atom-economy by minimizing functional group manipulations for preparing
allylating reagents. Due to the inadequacy of stereoselection
strategies, the asymmetric allylic C-H functionalization is still in the
early stage. In this essay, we will describe our journey to
identification of asymmetric catalytic systems, mechanism of allylic C-H
activation, control of stereo- and regioselectivity, and applications in
asymmetric synthesis.\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{longtable}[]{@{}l@{}}
\toprule
\textbf{Keywords}\tabularnewline
\midrule
\endhead
Allylic C-H functionalization\textbar{} palladium catalysis
\textbar{}cooperative catalysis \textbar{} allylic substitution
\textbar{} asymmetric catalysis\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
& \vtop{\hbox{\strut \textbf{Pu-Sheng Wang} (left) was born in 1988 in
Anhui, China. He received a B.S. in chemistry from University of Science
and Technology of China (USTC) in 2010. He went on to receive his Ph.D.
in organic chemistry from USTC in 2015 under the supervision of
Professor Liu-Zhu Gong. Then he worked as a postdoctoral fellow at USTC,
and he was promoted to associate professor in 2018, where his group's
work has focused on asymmetric catalysis and radical
chemistry.}\hbox{\strut \textbf{Liu-Zhu Gong} (right) was born in
October 1970 in Henan, China. He graduated from Henan Normal University
(1993) and received his Ph.D. (2000) from Institute of Chemistry,
Chinese Academy of Sciences. He was a visiting scholar (Joint Ph.D.
graduate student program) at the University of Virginia and an Alexander
von Humboldt Research Fellow at the University of Munich (2003--2004).
He was appointed an associate professor of Chengdu Institute of Organic
Chemistry, Chinese Academy of Sciences in 2000 and was promoted to a
full professor in 2001. Since 2006, he has been a full professor of
University of Science and Technology of China. He was appointed the
Cheung Kong Scholar Professor of organic chemistry in 2007. His research
interests include organocatalysis, organo/transition metal cooperative
and relay catalysis, allylic C--H functionalization, and
enantioselective total synthesis of natural products.}}\tabularnewline
\midrule
\endhead
\textbf{Left to Right:} Pu-Sheng Wang, Liu-Zhu Gong &\tabularnewline
\bottomrule
\end{longtable}

\section*{}

{\label{section}}

Contents

1. Introduction Page No.

2. Allylic C-H Cleaving Mode: Concerted Proton and Two-Electron Transfer
Process Page No.

3. Stereochemical Control Page No.

4. Regioselection Control Page No.

5. Applications Page No.

6. Conclusions Page No.

1. Introduction

Pd-catalyzed asymmetric allylic
substitutions,\textsuperscript{{[}1{]}}featuring abundantly available
chiral ligands, diverse bond-forming capacity and good functionality
tolerance, are synthetically useful
transformations\textsuperscript{{[}2{]}} to convert allylating reagents
to chiral allylic molecules (Scheme 1), and have exerted historical
impact on synthetic organic chemistry. However, pre-preparation of
active allylating reagents (e.g. allylic carbonates and allylic
carboxylates) is basically required for this type of reaction to
unavoidably necessitate additional work-up procedures. As a result,
either the step- or atom-economy of the entire process is to some degree
impaired. Alternatively, allylic C-H functionalization of olefins has
long been a solution of great interest to directly provide allylic
compounds by minimizing functionality manipulations for preparing
allylating reagents.\textsuperscript{{[}3{]}} Pd-catalyzed allylic C-H
activation generally occurs with highly electrophilic Pd(II) catalysts
under harsh conditions (Scheme 1). However, the presence of common
chiral ligands containing phosphorus or nitrogen donor atoms principally
deactivates the Pd(II) catalysts or causes incompatibility issues with
oxidizing conditions.\textsuperscript{{[}4{]}} Over the past few
decades, Pd-catalyzed asymmetric allylic C-H functionalization has
evolved rather slowly, presumably arising from the inadequacy of
stereochemical control strategies.\textsuperscript{{[}5{]}} In
combination with a chiral Lewis acid, White and co-workers established
an asymmetric allylic C-H
esterification,\textsuperscript{{[}6{]}}wherein the interaction of
chiral Lewis acid co-catalyst with \selectlanguage{greek}π-\selectlanguage{english}allyl-Pd intermediate is supposed
to impart the stereochemical outcome. Although only moderate levels of
enantioselectivity are obtained, it still represents a ground-breaking
example. Unfortunately, no follow-up reports appear on other
bond-forming reactions. Landmark work reported by Trost and co-workers
demonstrates that trivalent phosphorus derivatives are promising ligands
to promote Pd-catalyzed allylic C-H
functionalization.\textsuperscript{{[}7{]}} More importantly, chiral
phosphoramidite ligands derived from (\emph{S} )-BINOL are able to
control enantioselectivity, culminating in the first Pd-catalyzed
asymmetric allylic C-H alkylation of allylarenes with cyclic
1,3-diketones.\textsuperscript{{[}8{]}}

\textbf{Scheme 1} Pd-catalyzed asymmetric allylic substitution

Our research interest in this area stemmed from the experience in
asymmetric organo/transition-metal combined catalysis
(AOMC),\textsuperscript{{[}9{]}} which has grown to be a general concept
for the synergistically or sequentially integrating bond-breaking and
bond-forming events to stereoselectively build up molecular complexity.
Inspired by the successful examples of asymmetric allylic alkylation
reactions rendered by chiral enamine/palladium cooperative
catalysis,\textsuperscript{{[}10{]}} we initially attempted to establish
an asymmetric \selectlanguage{greek}α-\selectlanguage{english}allylation of ketones or aldehydes with a-olefins by
trapping the \selectlanguage{greek}π-\selectlanguage{english}allyl-Pd intermediate with a chiral
enamine.\textsuperscript{{[}5{]}} Unfortunately, the use of chiral
amines, even those capable of offering high enantioselectivity in
Pd-catalyzed Tsuji-Trost type reactions, was unable to afford
enantioselective allylic C-H alkylation reactions. Inspired by List's
work on chiral counteranion directed \selectlanguage{greek}α-\selectlanguage{english}allylation of
aldehydes,\textsuperscript{{[}11{]}} we successfully developed an
asymmetric allylic C-H alkylation of allylarenes and 1,4-dienes with
enolizable aldehydes (Scheme 2).\textsuperscript{{[}12{]}}

\textbf{Scheme 2} \selectlanguage{greek}α-\selectlanguage{english}Allylation of aldehydes with olefins enabled by
organo-metal cooperative catalysis

The initial success in asymmetric allylic C-H alkylation actually marked
our starting point to deeply get involved in this field and prompted us
to continuously endeavour to develop efficient catalyst systems, to
understand the reaction mechanism and stereochemical control models, and
to expand the applications in the enantioselective synthesis of natural
products and pharmaceutically interesting molecules.

2. Allylic C-H Cleaving Mode: Concerted Proton and Two-Electron Transfer
Process

Base-assisted proton abstraction has long been a widely accepted
mechanism for Pd-catalyzed allylic C-H activation to generate \selectlanguage{greek}π-\selectlanguage{english}allyl-Pd
intermediate (Scheme 3),\textsuperscript{{[}13{]}} and in most
cases\emph{p} -quinone derivatives are utilized as oxidants for Pd(II)
catalyst regeneration from Pd(0).\textsuperscript{{[}14{]}} Over our
course of the study, the interaction between \emph{p} -benzoquinone (BQ)
and the Pd(0)-phosphine complex draws our attention to re-investigate
the role of the \emph{p} -quinone oxidant. Motivated by the early
findings of the stable 16-electron {[}Pd(\emph{p}
-BQ)(PPh\textsubscript{3})\textsubscript{2}{]}\textsuperscript{{[}15{]}}and
{[}Pt(DQ)(CH\textsubscript{2}=CH\textsubscript{2})(PCy\textsubscript{3}){]}\textsuperscript{{[}16{]}}(DQ
= duroquinone) complexes (Scheme 3), we speculated that a 16-electron
Pd(0) complex bearing a trivalent phosphorus ligand, a\emph{p} -quinone,
and an alkene might be an active intermediate for allylic C-H cleavage.
In collaboration with Hong group, a set of 16-electron metal complexes
and C--H activation transition states (\textbf{TS-1} ) for both Pd and
Pt catalysis were computed to evaluate the feasibility of allylic C--H
activation\textsuperscript{{[}17{]}}(Scheme 3). To our delight, the
computational results suggest a concerted proton and two-electron
transfer process to cleave the allylic C-H bonds, and the intrinsic
low-energy barriers (14-21 kcal/mol) are in accordance with the
experimental results, in which both Pd and Pt catalysis can allow a wide
range of \selectlanguage{greek}α-\selectlanguage{english}alkenes to undergo allylic C--H alkylation with soft carbon
nucleophiles. Notably, in comparison with triarylphosphines, BINOL-based
phosphoramidite ligands mostly exhibit superior performance in both the
reaction conversion and the scope of carbon
nucleophiles.\textsuperscript{{[}18{]}}

\textbf{Scheme 3} Pd-mediated allylic C-H activation

3. Stereochemical Control

Three general strategies were proposed to control the enantioselectivity
of Pd-catalyzed allylic C-H
functionalization\textsuperscript{{[}5{]}}(Scheme 4). The adoption of
chiral organocatalysts in imparting stereoselection is our initial
strategy, wherein chiral organocatalyst can interact with the
nucleophile to stereoselectively direct the addition to \selectlanguage{greek}π-\selectlanguage{english}allyl-Pd
intermediate generated in situ from Pd-mediated cleavage of the allylic
C-H bonds (Scheme 4a). Since either or both the ligand and
organocatalyst can be chiral, this strategy provides more options to
control the stereoselectivity. Chiral ligands always play a key role in
the development of asymmetric metal-catalyzed reactions. Thus, bulky
chiral phosphoramidite ligands were synthesized and evaluated for the
Pd-catalyzed allylic C-H functionalization reactions (Scheme
4b).\textsuperscript{{[}19{]}} These ligands, easily accessed from
3,3'-substituted BINOL/H\textsubscript{8}-BINOL and amines, feature high
structural flexibility and tunability to allow for the buildup of a
large library of chiral phosphoramidites that are requisite for
identification of the best chiral catalysts and rapid optimization of
reaction conditions. Organo-metal relay/sequential catalysis is the
third general strategy to access the enantioselective functionalization
of allylic C-H bonds (Scheme 4c), wherein active allyl species generated
from the Pd-catalyzed allylic C-H activation participate in the
organocatalytic asymmetric transformation, leading to chiral allylic
products.

\textbf{Scheme 4} General modes for stereochemical control in the
allylic C-H functionalization

After the asymmetric allylic C-H alkylation of allylarenes with
enolizable aldehydes was established (Scheme 2), the concept was
expanded to a similar reaction of 1,4-dienes (Scheme
5a).\textsuperscript{{[}12b{]}} In both cases, the palladium complexes
of triarylphosphines were the most efficient catalysts for allylic C-H
activation in combination with chiral phosphoric acid to generate chiral
\selectlanguage{greek}π-\selectlanguage{english}allyl-Pd phosphate intermediates that could couple with enamines
formed from achiral primary amine and aldehydes via transition
state\textbf{TS-2} , in which the phosphate anion was supposed to
provide a chiral environment for the stereoselective C-C bond-forming
event. The design of the chiral catalyst for enantioselective allylic
C-H alkylation of pyrazol-5-ones with allylarenes got inspiration from
the allylic alkylation between pyrazol-5-ones and allylic alcohols
enabled by Pd/phosphoric acid cooperative catalysis (Scheme
5b).\textsuperscript{{[}20{]}} As a consequence, the combination of
chiral phosphoramidite-Pd catalyst and chiral phosphoric acid allowed
the allylic C-H alkylation reaction to proceed via the transition state
(\textbf{TS-3} ) and offered the highest
enantioselectivity.\textsuperscript{{[}21{]}}

\textbf{Scheme 5} Enantioinduction via organo-metal cooperative
catalysis

Apart from organo-metal cooperative catalysis, organo-metal relay
catalysis\textsuperscript{{[}22{]}} was also viable for realizing
asymmetric allylic C-H functionalization (Scheme 6). In 2015, we
described a highly diastereoselective carbonyl allylation of aldehydes
with \selectlanguage{greek}α-\selectlanguage{english}olefins,\textsuperscript{{[}23{]}} proceeding via a sequential
process consisting of a Pd-catalyzed oxidative allylic C-H borylation
and a Br\selectlanguage{ngerman}ønsted acid-catalyzed allylboration of aldehydes. The use of
chiral phosphoric acid as co-catalyst offered the desired allylation
product with 67\% ee. In addition, the relay catalysis of chiral
bifunctional squaramide and palladium complex enabled an asymmetric
{[}2+2+1{]} annulation reaction of allyl ketones, barbituric acids and
nitroalkenes\textsuperscript{{[}24{]}} to generate highly functionalized
cyclopentanes with high levels of stereoselectivities. Mechanistic
studies suggested that chiral squaramide catalyst engaged in both the
initial intermolecular and the final intramolecular Michael addition
steps to enhance the enantioselectivity by kinetic resolution.

\textbf{Scheme 6} Organo-metal relay catalytic reactions involving
allylic C-H functionalization

To address incompatibility issues encountered in organo/metal relay
catalysis, sequential catalysis\textsuperscript{{[}25{]}} was introduced
to fulfil asymmetric allylic C-H functionalization processes (Scheme 7).
In the presence of chiral bis(pinanediolato)diboron reagent,
Pd-catalyzed oxidative allylic C\selectlanguage{english}-H borylation of allylarenes furnished a
chiral allylboronate intermediate,\textsuperscript{{[}26{]}} which
sequentially underwent chiral phosphoric acid-catalyzed allylboration of
aldehydes to give homoallylic alcohols with excellent levels of
stereoselectivity (Scheme 7a). In particular, the extension of such
relay catalysis concept to allyl ethers met with great
success.\textsuperscript{{[}27{]}} The sequential catalysis of platinum
complex and bifunctional chiral urea
catalyst\textsuperscript{{[}17b{]}}could work in similar manner to drive
a one-pot process of asymmetric Michael addition and allylic C--H
alkylation, leading to chiral tetrahydropyrans (Scheme 7b).

\textbf{Scheme 7} Organo-metal sequentially catalyzed reactions
involving allylic C-H functionalization

Even though organo-palladium combined catalysis has afforded a variety
of asymmetric allylic C-H functionalization reactions, this strategy is
seemingly workable for a limited number of nucleophiles presumably due
to the incompatibility between the conditions of organocatalysis and
allylic C-H activation. As such, chiral ligands have been continuously
prepared and evaluated for the establishment of asymmetric allylic
substitution reactions.\textsuperscript{{[}1b{]}} In 2015, we
accomplished a Pd-catalyzed enantioselective intramolecular allylic C\selectlanguage{english}-H
oxidation by using BINOL-based bulky chiral phosphoramidites as ligands,
allowing rapid synthesis of chiral chromans with high levels of
stereoselectivity (Scheme 8).\textsuperscript{{[}28{]}} In addition,
chiral phosphoramidite-palladium catalysis was also viable for promoting
asymmetric intramolecular allylic C\selectlanguage{english}-H amination reactions to build
chiral tetrahydroquinazoline scaffolds (Scheme
8).\textsuperscript{{[}29{]}} For 1,4-dienes bearing an additional
arylethene-1-sulfonyl moiety, a sequential process consisting of
enantioselective intramolecular allylic C\selectlanguage{english}-H amination and Diels\selectlanguage{english}-Alder
reaction resulted in the formation of chiral fused tricyclic
tetrahydropyrimidines. Furthermore, Pd-catalyzed intermolecular
asymmetric allylic C-H alkylation of 1,4-dienes could be achieved by
using a chiral phosphoramidite ligand (Scheme
8).\textsuperscript{{[}30{]}} In addition, either
5-alkylthiazol-4(5H)-ones or cyclic \selectlanguage{greek}β-\selectlanguage{english}ketoesters smoothly gave linear
allylic alkylation products with high levels of enantioselectivity.

\textbf{Scheme 8} Enantioselectivity induced by chiral phosphoramidite
ligands

4. Regioselection Control

In Pd-catalyzed allylic substitution reactions with soft nucleophiles,
the bond-forming event basically occurs via the outer-sphere
nucleophilic addition to the \selectlanguage{greek}η\selectlanguage{english}\textsuperscript{3}-allylpalladium
intermediate.\textsuperscript{{[}1c{]}} The regioselectivity is mainly
controlled by the steric hindrance of the allyl moiety and thus, the
terminal carbon of monosubstituted allyl substrates is preferentially
attacked by nucleophiles to give the linear products (Scheme 9a). In
sharp contrast, the branch- and enantioselective allylic substitution
reactions are much more difficult to access by palladium catalysis. To
date, only a few examples have been reported to preferentially give
branched allyl products by tuning ligands to induce
S\textsubscript{N}1-type characteristics of allylpalladium
species.\textsuperscript{{[}31{]}} With regard to chiral phosphoramidite
ligands, the typical behavior of mono-ligation to Pd offers the binding
site for a suitable nucleophile,\textsuperscript{{[}32{]}} thus opening
the possibility of forming the branched product via an inner-sphere
S\textsubscript{N}2'-pathway\textsuperscript{{[}33{]}} (Scheme 9b).

\textbf{Scheme 9} Correlation between regioselection and ligand

Our efforts toward the control of regioselectivity started from
understanding how the nucleophile-dependent regioselective allylic C-H
alkylation of 1,4-dienes worked (Scheme 10). Through the screening of
chiral phosphoramidite ligands and reaction conditions,
pyrazol-5-ones\textsuperscript{{[}21{]}} and
5-alkylthiazol-4(5H)-ones\textsuperscript{{[}30a{]}} preferred to afford
chiral C5-branched and \emph{E} -dienyl products, while
azlactones,\textsuperscript{{[}17a{]}} glycine Schiff
bases\textsuperscript{{[}34{]}} and \selectlanguage{greek}α-\selectlanguage{english}angelica
lactones\textsuperscript{{[}35{]}} tended to give thermodynamically
unfavorable chiral C5-branched and \emph{Z} -dienyl products.
Computational studies suggested that the \emph{E/Z} - and
regioselectivities were governed by the geometry and coordination
pattern of nucleophiles.\textsuperscript{{[}17a{]}} Comparing the two
competing transition states \textbf{TS-4} and \textbf{TS-5} , both were
able to provide the branched products via an
S\textsubscript{N}2'-pathway, but the former showed a more stable but
longer vinyl \selectlanguage{greek}π-\selectlanguage{english}allyl-Pd fragment (4.9 \selectlanguage{ngerman}Å \emph{vs} 4.5 Å), therefore,
the\emph{E/Z} -selectivity was conquered by the geometric match of the
vinyl \selectlanguage{greek}π-\selectlanguage{english}allyl-Pd fragment, the geometry of the nucleophile and the
distortion of Pd-nucleophile bonding. With the use of 2-acylimidazoles
or coordinating \selectlanguage{greek}α-\selectlanguage{english}aryl carbonyls as nucleophiles,
1,4-dienes,\textsuperscript{{[}36{]}} allyl
ethers\textsuperscript{{[}37{]}} and
N-allylimines\textsuperscript{{[}38{]}} all performed well to generate
branched products with high levels of regio- and enantioselectivity.
Recently, by using \selectlanguage{greek}α-\selectlanguage{english}benzothiazylacetamides and \selectlanguage{greek}α-\selectlanguage{english}heteroaryl ketones as
nucleophiles, we established a branch- and enantioselective allylic C--H
alkylation capable of accommodating diverse types of \selectlanguage{greek}α-\selectlanguage{english}alkenes, ranging
from 1,4-dienes and allylarenes to unactivated \selectlanguage{greek}α-\selectlanguage{english}alkenes tethering a
wide scope of appended functionalities.\textsuperscript{{[}39{]}} Apart
from carbon-carbon bond formation, the inner-sphere pathway was also
amenable for the branch- and enantioselective construction of
carbon-nitrogen bond via the direct coupling of allylic C-H bonds and
aniline, albeit with only moderate enantioselectivity (Scheme
9).\textsuperscript{{[}40{]}}

\textbf{Scheme 10} Branch- and enantioselective allylic C--H alkylation

5. Applications

Pd-catalyzed asymmetric allylic C-H functionalization reactions provide
a straightforward approach to access optically active starting materials
or synthetically useful building blocks (Scheme 11). Starting with the
asymmetric intramolecular allylic C-H oxidation, chiral chroman
skeletons were smoothly given to allow the enantioselective syntheses of
(+)-diversonol,\textsuperscript{{[}28{]}} gonytolide
C\textsuperscript{{[}41{]}} and ascherxanthone
A.\textsuperscript{{[}42{]}} In addition, asymmetric intramolecular
allylic C-H amination is able to provide chiral tetrahydroquinazolines
that can serve as key intermediates for the synthesis of highly
enantioenriched letermovir.\textsuperscript{{[}29{]}} Furthermore,
regio- and stereoselective allylic C-H alkylation reactions generate a
range of key building blocks to access natural products, e.g.
lepadiformine marine
alkaloids,\textsuperscript{{[}17a{]}}tanikolide\textsuperscript{{[}30b{]}}
and aigialmycin D,\textsuperscript{{[}27{]}} and biologically important
unnatural molecules, e.g. focalin,\textsuperscript{{[}38{]}} tachykinin
receptor antagonist\textsuperscript{{[}37{]}} and Taniguchi
lactone.\textsuperscript{{[}39{]}}

\textbf{Scheme 11} Applications of asymmetric allylic C--H
functionalization reactions to the synthesis of natural products and
bioactive substances

6. Conclusions

Over the past decade, Pd-catalyzed asymmetric allylic C-H
functionalization has shown great potential as a general platform to
access densely functionalized chiral molecules from easily available
alkenes. In this essay, we briefly present our journey to the
development of asymmetric catalytic systems, the mechanism of allylic
C-H activation, the control of stereo- and regioselectivity, and the
applications in asymmetric synthesis of natural products and bioactive
substances. The use of asymmetric organo/palladium combined catalysis
and the development of a library of structurally tunable and bulky
chiral phosphoramidite ligands have opened new avenues to create regio-
and enantioselective Pd-catalyzed allylic C-H functionalization
reactions. The palladium complex of a phosphorus ligand and\emph{p}
-quinone oxidant turns out to be an active catalyst and allows the
cleavage of the allylic C-H bond via an unprecedented concerted proton
and two-electron transfer process. Experimental and computational
studies have shown that the high levels of stereo- and
branch-selectivity are not only governed by the coordination pattern of
nucleophiles, but also regulated by the monoligation of chiral
phosphoramidite ligands to allow for a nucleophile-coordination enabled
inner-sphere S\textsubscript{N}2'-pathway. The Pd-catalyzed asymmetric
allylic C-H functionalization reactions are applicable to the rapid
access of synthetically useful building blocks, enabling the asymmetric
synthesis of a range of natural products and biologically active
molecules. Notably, the strategies and concepts presented here for
cleaving allylic C-H bonds and controlling selectivity are generally
applicable. Hopefully, this essay will provide some inspiration for the
rational design of new asymmetric allylic C-H functionalization
transformations and prompt future ground-breaking discoveries in this
field.

Acknowledgement

We are grateful for financial support from the National Key R\&D Program
of China (2021YFA1500100), Youth Innovation Promotion Association CAS
(2020448), NSFC (22171254 and 22188101), Anhui Provincial Natural
Science Foundation (2108085MB58), USTC Research Funds of the Double
First-Class Initiative (YD2060002024) and Start-up Research Fund from
University of Science and Technology of China (KY2060000216).

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model. \emph{Acc. Chem. Res.} \textbf{2006,} \emph{39}, 747-760. (b) Lu,
Z.; Ma, S., Metal-catalyzed enantioselective allylation in asymmetric
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(The following will be filled in by the editorial staff)\tabularnewline
Manuscript received: XXXX, 2022 Manuscript revised: XXXX, 2022
Manuscript accepted: XXXX, 2022 Accepted manuscript online: XXXX, 2022
Version of record online: XXXX, 2022\tabularnewline
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\textbf{Entry for the Table of Contents}\selectlanguage{english}
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\textbf{Pd-Catalyzed Asymmetric Allylic C-H Functionalization} Pu-Sheng
Wang, Liu-Zhu Gong* \emph{Chin. J. Chem.} \textbf{2023}, \emph{40},
XXX---XXX. \textbf{DOI: 10.1002/cjoc.202200XXX}\tabularnewline
This essay presents recent advances in Pd-catalyzed asymmetric allylic
C-H functionalization in our lab, including the development of
asymmetric catalytic systems, the mechanism of allylic C-H activation
and the control of stereo- and regioselectivity. A diverse range of
\selectlanguage{greek}α-\selectlanguage{english}alkenes have been active allylic reagents to engage in the reactions
to access synthetically useful building blocks, enabling the asymmetric
synthesis of a range of natural products and biologically
molecules.\tabularnewline
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