Pd-Catalyzed Redox Divergent Coupling of Ketones with Terpenols

Chao-Yang Zhao, Ding-Wei Ji, Hao Zheng, Gu-Cheng He, Heng Liu, Yan-Cheng Hu,

Research Article

Pd-Catalyzed Redox Divergent Coupling of Ketones with Terpenols

and Qing-An Chen*

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ABSTRACT: Redox diversity is a common and important feature

of nature. Herein, a Pd-catalyzed redox divergent coupling of

ketones with terpenols has been developed to access α-substituted

ketones with varying degrees of unsaturation. The control of

oxidation states of the product is facilitated by employing diﬀerent

additives. With the aid of BnOH as an external hydrogen source, a

reductive coupling pathway is thermodynamically favored. The use

of LiBr as the additive will reduce the reactivity of Pd−H to divert

the selectivity toward α,β-unsatuated ketones. By switching the

solvent from toluene to chlorobenzene, the active species Pd−H

will be fully quenched to enable oxidative coupling. Gram-scale

reaction with lower catalyst loading (0.5 mol %) was also

accomplished to highlight the practicability of this protocol.

Furthermore, detailed experimental studies were carried out to elucidate the reaction mechanism and the factors enabling

manipulation of the redox selectivity. This redox divergent coupling protocol provides an important complement for known

precedents on Tsuji−Trost allylation of ketones.

KEYWORDS: redox diversity, ketones, terpenols, reductive coupling, oxidative coupling

edox metabolism has been recognized as one of the most

important metabolic pathways in organisms. With the

formation of π-allyl palladium intermediates from substrates

with leaving groups (X, NR₂, OCO R, CO R, OR,

2 2

aid of various redox enzymes, this metabolite will create

OH, etc.). On the other hand, stereo-, regio-, and

chemodivergent strategies are the state-of-the-art in the

important bioactive metabolites with diﬀerent redox states.

For example, as the primary photoreceptor molecule of vision,

rhodopsin (also known as visual purple) consists of the protein

opsin linked to 11-cis-retinal. A light absorption leads to the

isomerization of the 11-cis-retinal group of rhodopsin to its all-

generation of molecular diversity. Since redox diversity is

ubiquitous in nature, we envisioned that the redox strategy

might be also employed to expand the diversity of chemical

catalytic allylation reactions. As a naturally and industrially

abundant feedstock, prenol is a green precursor of terpenoids

trans form and the generation of a nerve impulse. Retinal and

retinol (vitamin A) can undergo mutual conversion catalyzed

and their derivatives. Following our long-standing interest in

by oxidoreductase. In addition, retinal can be further oxidized

pursuing divergent selective transformations of terpenes, we

sought to develop a Pd-catalyzed redox divergent coupling of

ketones with terpenols (Scheme 1c). The major challenge of

this proposal is the construction of C−C bond with varying

degrees of unsaturation. It provides an important complement

for known precedents on Tsuji−Trost allylation of ketones.

Initially, we chose 1-tetralone (1a) and prenol (2a) as the

to retinoic acid in the presence of ALDH (aldehyde

dehydrogenase, Scheme 1a). With respect to artiﬁcial

processes, hydrogenation and dehydrogenation are two

important methods to change the redox state of compounds.

The transition-metal-catalyzed dehydrogenation has achieved

rapid development in recent years. However, most of the

current research focuses on monoredox transformation.

Therefore, it is of great signiﬁcance to realize the

corresponding regulation of redox divergent couplings with

artiﬁcial catalysts.

model substrates to attempt Pd-catalyzed redox divergent

coupling. In the presence of [η -allylPdCl] , N-heterocyclic

Received: April 1, 2021

Revised: May 12, 2021

Published: May 27, 2021

α-Substituted carbonyl compounds are common motifs in

natural products and can be widely found in most of the top

00 prescription drugs. In the past few decades, many elegant

Pd-catalyzed Tsuji−Trost allylation reactions have been

demonstrated to produce α-allyl ketones (Scheme 1b).

One of the general features of this transformation is the

2021 American Chemical Society

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Scheme 1. Redox Diversity-Oriented Synthesis

carbene ligand (SIPr·HCl), and aniline, three products

including reductive alkylated ketone 3a, α,β-unsaturated

ketone 4a, and normal allylated ketone 6a were obtained in

low selectivities. Of note is that aniline could be almost

completely recovered, thus suggesting aniline serves as a

cocatalyst (Table 1, entry 1). The yield and selectivity

decreased dramatically when the reaction was performed

under air atmosphere (entry 2). The use of BINAP as ligand

gave low conversion of 1a (entry 3). With a view to obtain the

reductive coupling product 3a, an external hydrogen source

would be required. Therefore, diﬀerent alcohols including

MeOH, BuOH, and BnOH were further examined (entries 4−

6). Delightedly, when BnOH was engaged in the reaction, the

yield of 3a was signiﬁcantly increased to 92%, and no other

products were detected (entry 6). In contrast, by varying the

additives to bromide salts such as KBr, NaBr, and LiBr, 4a

turned out to be predominant (entries 7−9). It may be

because LiBr could decrease the hydrogenation ability of Pd−

H, thereby preventing further hydrogenation of 4a. The

employment of 4-aminopyridine as cocatalyst provided a better

result (entry 10). The yield of 4a could be improved to 72% at

an elevated temperature in the presence of precatalyst [η -

cinPdCl] (entry 11). Surprisingly, when PhCl was used as

solvent, oxidative coupling product 5a was exclusively obtained

(

entry 12). The secondary amine piperidine was found to be a

better cocatalyst (entry 13). Increasing the amount of MeONa

led to a further improvement of the yield of 5a (entry 14).

With the optimized conditions in hand, we subsequently

explored the substrate scope of this redox divergent protocol.

As demonstrated in Table 2, for reductive couplings, subjecting

unsubstituted 1-tetralone 1a to the standard conditions

Table 1. Optimization for Pd-Catalyzed Redox Divergent Coupling

yield (%)

entry

amine

PhNH₂

additive

sol

Tol

PhCl

MeOH

^tBuOH

BnOH

KBr

NaBr

LiBr

PhNH₂

4-aminopyridine

PhNH₂

piperidine

LiBr

Conditions: 1a (0.20 mmol), 2a (0.30 mmol), [η -allylPdCl] (2.5 mol %), SIPr•HCl (5 mol %), MeONa (1.5 equiv), additive (1.5 equiv),

solvent (0.6 mL), 70 °C. Determined by GC-FID analysis of the crude product mixture using mesitylene as internal standard. Under air

atmosphere. BINAP instead of SIPr·HCl. MeONa (1.0 equiv). [η -cinPdCl] instead of [η -allylPdCl] 80 °C. MeONa (3.0 equiv); Isolated

yield. Tol = Toluene; PhCl = Chlorobenzene.

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Table 2. Ketone Scope for Pd-Catalyzed Reductive

Coupling

Table 3. Ketone Scope for Pd-Catalyzed Migratory

Coupling

Using (SIPr)Pd(cin)Cl (2.5 mol%) directly.

We next set about to assess the scope with respect to the

oxidative coupling conditions (Table 4). The model substrate

Using (SIPr)Pd(allyl)Cl (2.5 mol%) directly. BnOH (0.25 eq.). 2a

(1.0 eq.). Without BnOH. MeOH was used as the solvent.

Table 4. Ketone Scope for Pd-Catalyzed Oxidative Coupling

furnished 3a in 92% yield. 4-Me-1-tetralone 1b underwent this

alkylation smoothly at 70 °C to provide 3b in 85% yield.

Substrates bearing a methoxyl group on the phenyl ring,

regardless of its positions, were all well tolerated (3c−e),

providing the corresponding ketones in good yields. 7-Me and

-F on the phenyl ring were also compatible with this process

and gave the products (3f−g) in satisfactory yields. However,

in the cases of 7-Cl- and 7-Br-derived substrates, dehalo-

genated products were obtained (see Scheme S1). Further-

more, this transformation could be extended to 1-indanone

(

1h, ﬁve-membered ring) and 1-benzosuberone (1i, seven-

membered ring). Notably, noncyclic ketones were also

applicable to the current protocol, and the α-alkylated ketones

could be successfully produced in 46%−93% yields (3j−l).

Unfortunately, aryl ketones with ester and nitro substituents

and pyridine-fused cyclohexanone were not tolerated (see

Scheme S1). Additionally, the attempts to induce the

enantioselectivity with chiral amine catalysts all failed (see

Scheme S2).

The ketone scope for the Pd-catalyzed migratory coupling

was further surveyed (Table 3). By adding LiBr, simple ketone

(

SIPr)Pd(allyl)Cl (0.5 mol%), MeONa (2.0 eq.). MeONa (1.5

eq.).

1a could be transformed into the α,β-unsatuated ketone 4a in

72% yield through hydrogen migration. The E-conﬁguration of

4a was determined via two-dimensional nuclear magnetic

resonance spectroscopy (NOESY). Substrates possessing

electron-donating groups, such as −OMe and −Me, all reacted

smoothly to produce the corresponding products in good

yields (76−87%) and good selectivities (4b−4f). The ﬂuoro

group on the phenyl ring was also well tolerated and gave the

ketone 4g in 74% yield with 14:1 E/Z. Moreover, the ketone

bearing a 5-membered ring was applicable to the coupling as

well albeit with a slightly decreased yield (4h). Notably, the 7-

membered ring derived ketone was eﬃciently converted to the

corresponding product 4i in 84% yield with excellent

selectivity.

1a was converted into the desired product 5a in 93% yield. It is

worth noting that the process could still proceed with high

eﬃciency (90% yield) with the catalyst loading being reduced

to 0.5 mol %. Moreover, a range of 1-tetralones with

substituents at the 4-, 6-, or 7-positions all worked well in

this protocol to give products 5b−5f in 78−94% yields.

Remarkably, substrates with either a 5-membered ring or 7-

membered ring were all compatible with the current conditions

and produced the highly unsaturated ketones (5g−i) in good

to excellent yields. In all cases, the products were obtained with

exclusive E-stereoselectivity, and the conﬁguration was further

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Table 5. Terpenol Scope for Pd-Catalyzed Redox Divergent Coupling

Condition A: [η -allylPdCl] (2.5 mol %), SIPr·HCl (5 mol %), PhNH (50 mol %), PhCH OH (25 mol %), MeONa (1.5 eq.), Tol, 70 °C.

Condition B: [η -cinPdCl] (2.5 mol%), SIPr·HCl (5 mol %), 4-Aminopyridine (50 mol %), LiBr (1.5 eq.), MeONa (1.0 eq.), Tol, 80 °C.

Condition C: [η -allylPdCl] (2.5 mol %), SIPr·HCl (5 mol %), Piperidine (50 mol %), MeONa (1.5 eq.), PhCl, 70 °C.

Scheme 2. Kinetic Studies

Determined by GC-FID analysis of the crude product mixture using mesitylene as internal standard.

conﬁrmed by two-dimensional nuclear magnetic resonance

spectroscopy (NOESY) of product 5a.

all of the products (5ab−ad) were produced in good yields

(83−91%).

Subsequently, we turned our attention toward the scope of

various terpenols using the current redox divergent coupling

strategy (Table 5). Terpenols bearing two or more isoprene

units, such as geraniol (2b), farnesol (2c), and phytol (2d), all

proceeded smoothly to deliver the reductive coupling products

Additional control experiments were further conducted to

elucidate the mechanism of this redox divergent coupling

protocol. First, the kinetic studies for the couplings under

conditions A and B were carried out, and the results are shown

in Scheme 2. For reductive coupling, a volcano-shaped

correlation was observed between the yield of 5a and the

reaction time (Scheme 2a). In addition, the yield of α,β-

unsatuated ketone 4a displayed a moderate positive correlation

with the yield of 5a. A sigmoidal kinetic curve was observed for

the desired product 3a (Scheme 2a). These results suggest that

unsaturated ketones 4a and 5a are probably the intermediates

of the reaction and can be transformed into saturated ketone

3a through further reduction. For the coupling under

(3ab−ad) in good yields (78−87%, condition A). Under the

conditions B, these substrates were also tolerated, giving the

expected products (4ab−ad) in good stereoselectivity but with

moderate yields, mainly because 1-tetralone 1a could not be

totally consumed. For the oxidative coupling reactions, the

number of isoprene units in the terpenol substrates also

exhibited no signiﬁcant inﬂuence on the reactive eﬃciency, and

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conditions B (Scheme 2b), the nearly ﬂat yield curve of 5a

indicates that its formation rate is close to its consumption rate

Table 6. Eﬀect of MeONa on the Redox State

(

2−13 h). The yield of α,β-unsatuated ketone 4a increased

with the reaction time under conditions B. The comparison of

the reaction rate under conditions A and B reveals that the

addition of LiBr greatly reduced the catalyst’s turnover

frequency [k_a_v_g(3a vs 4a) = 0.14 vs 0.02 mmol/h]. It is

noteworthy that allylated product 6a was not detected at all

under conditions B.

The interconversions of these three redox divergent

products were subsequently performed (Scheme 3a). The

entry

MeONa (eq )

3a (%)

4a (%)

5a (%)

6a (%)

0.02

0.50

1.00

1.50

Scheme 3. Interchange Conversions and Gram-Scale

Reaction

Determined by GC-FID analysis of the crude product mixture using

mesitylene as internal standard.

Scheme 4. Isotopic Labeling Studies

Determined by GC-FID analysis of the crude product mixture using

mesitylene as internal standard.

oxidative product 5a could be readily transformed into

saturated ketone 3a and α,β-unsaturated ketone 4a under

conditions D and E, respectively. In addition, 3a could also be

easily obtained in 90% yield from 4a under condition E

(Scheme 3a). Additionally, BnOH has no obvious eﬀect on the

For the oxidative coupling, an expected prenal 7a and an

unexpected aldehyde 7b were simultaneously observed in the

absence of 1-tetralone 1a (Scheme 5a). Highly unsaturated

aldehyde 7b originates from the self-condensation of prenal

interchange conversions. Remarkably, the reductive coupling

still took place smoothly to furnish 3a in gram scale (1.314 g)

with 76% yield at very low catalyst loading (0.5 mol %, Scheme

b).

The amount of MeONa had a signiﬁcant eﬀect on the

7a. This result demonstrates that prenal 7a, formed by β-H

elimination, is likely the precursor of 5a, and the resulting Pd−

H can be quenched by PhCl to furnish PhH. To further probe

the reaction mechanism, a kinetic experiment for the oxidative

coupling of 1-tetralone 1a and prenol 2a was carried out.

Surprisingly, this coupling proceeded very fast and accom-

plished within 60 min. Meanwhile, a large amount of benzene

was formed, suggesting that PhCl could quench the reductive

Pd−H species to prevent further reduction of 5a (Scheme 5b).

A small amount of benzene was also detected when NHC-Pd

was prepared in situ with MeONa in PhCl (Scheme 5c). It

indicates that benzene is partially produced from the reaction

of PhCl with MeONa in the presence of palladium.

Several control experiments have been designed to interpret

the role of amine during this redox-divergent coupling

(Scheme 6). For the formation of ketone 5a, external amine

could increase the condensation reactivity in the presence of

MeONa (Scheme 6a). Compound 5a cannot be obtained

when aniline was solely introduced because the strong base

selectivity of this redox divergent coupling reaction (Table 6).

When the amount of MeONa was increased, the ratio of 3a/4a

increased signiﬁcantly. This phenomenon indicates that in

addition to a base, MeONa likely also serves as a hydrogen

source in the process. This speculation was further supported

by the isotopic labeling studies (Scheme 4). In the presence of

CD ONa (2.0 equiv), the reductive coupling of prenol 2a with

-tetralone 1a delivered deuterio-3a-d in 69% yield with

deuterium being scrambled into all branched alkyl carbons

Scheme 4a, top). Under migratory coupling condition B, a

similar deuterium scrambling result was observed on deuterio-

a-d (Scheme 4a, middle). The oxidative coupling product 5a-

(

d was obtained in 92% yield with 4% deuterium being

incorporated at terminal methyl groups (Scheme 4a, bottom).

The deuterium incorporation at terminal methyl groups of 3a-

d, 4a-d, and 5a-d illustrates that enol isomerization of 5a is

involved during the reaction (Scheme 4b).

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Scheme 5. Mechanistic Studies for Oxidative Coupling of 1a

and 2a

In order to better clarify the role of chlorobenzene in the

oxidative coupling of 1-tetralone 1a and prenol 2a, a set of aryl

halides including para-substituted chlorobenzenes with diﬀer-

ent electronic properties, bromo- and iodobenzene were

selected as the solvents (Scheme 7). All of the reactions led

Scheme 7. Solvent Eﬀect on the Formation of 5a

Determined by GC-FID analysis of the crude product mixture using

mesitylene as internal standard.

to the formation of a large amount of dehalogenated arenes.

The solvents exerted a signiﬁcant inﬂuence on the outcome,

and PhCl oﬀered the best result.

Determined by GC-FID analysis of the crude product mixture using

mesitylene as internal standard.

On the basis of the above observations and previous work, a

plausible mechanism for the redox divergent coupling was

proposed (Scheme 8). Under the condition C for the oxidative

coupling, the catalyst precursor undergoes reductive elimi-

nation to generate Pd(0) species B. A subsequent oxidative

addition of chlorobenzene with B yields phenyl-Pd(II)

complex C. The direct ligand exchange of Pd(II) complex C

with MeONa forms a MeO-Pd-Ph species which undergoes β-

H elimination and reductive elimination successively to form

benzene as side product and rebound to Pd(0) species B. An

alternative deprotonation of prenol 2a with C forms benzene

as a byproduct. Meanwhile, it also generates alkoxide-Pd(II)

intermediate D which undergoes β-H elimination to generate

prenal 7a and Pd(II)-hydride E. Pd(0) species B is regenerated

from a reductive elimination of E. Highly unsaturated ketone

Scheme 6. Control Studies on the Role of External Amine

a could be produced from the coupling of 1-tetralone 1a with

prenal 7a promoted by external amine.

Under the condition B for the migratory coupling, the

alkoxide-Pd(II) intermediate D is generated from the

deprotonation of prenol 2a with catalyst precursor A (Scheme

Determined by GC-FID analysis of the crude product mixture using

mesitylene as internal standard.

). Then ketone 5a could be obtained via same pathway

(

MeONa) is crucial for the process. The ﬁrst transfer

aforementioned. In the absence of chlorobenzene, Pd(II)-

hydride F could be formed reversibly from the oxidation of

Pd(0) species B with alcohol (prenol 2a, MeOH, or BnOH).

The coordination of Pd(II)-hydride F with ketone 5a gives

complex G. A subsequent hydride transfer delivers vinylogous

hydrogenation of 5a to α,β-unsatuated ketone 4a was partially

suppressed by the addition of amine (Scheme 6b). However,

no negative eﬀect of amine was observed in the second transfer

hydrogenation of 4a to saturated ketone 3a.

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Republic of China; orcid.org/0000-0002-9129-2656 ;

Research Article

Scheme 8. Proposed Mechanism for Redox Divergent Coupling

enolate H. The ﬁnal protonolysis of H with prenol 2a yields

the migratory coupling products 4a and regenerates alkoxide-

Pd(II) intermediate D. Further reduction of α,β-unsaturated

ketone 4a will furnish saturated ketone 3a. The addition of

LiBr can prevent further transfer hydrogenation of 4a, likely

because LiBr can change the environment around the Pd

center, which may have an eﬀect on the activity of the Pd−H

species.

In conclusion, a practical strategy for the redox divergent

coupling of ketones with terpenols has been developed under

palladium catalysis. Manipulation of the selectivity was

governed by the choice of diﬀerent additives. Utilization of

BnOH as an additive aﬀorded reductive coupling products

with high selectivity, while LiBr additive enabled selective

synthesis of migration coupling product. Moreover, using PhCl

as solvent, oxidative coupling products can be obtained with

high selectivity. A gram-scale reaction has also been

demonstrated with lower catalyst loading (0.5 mol %) to

highlight the practicality of this protocol. Furthermore, detailed

experimental investigations were conducted to interpret the

reaction mechanism and the factors enabling manipulation of

the redox selectivity. This redox divergent coupling protocol

complements traditional precedents of Tsuji−Trost allylation

of ketones. Further studies on exploitation of new redox

divergent couplings of terpenols are underway in our

laboratory.

Email: qachen@dicp.ac.cn

Authors

Chao-Yang Zhao − Dalian Institute of Chemical Physics,

Chinese Academy of Sciences, Dalian 116023, People’s

Republic of China; University of Chinese Academy of

Sciences, Beijing 100049, People’s Republic of China

Ding-Wei Ji − Dalian Institute of Chemical Physics, Chinese

Academy of Sciences, Dalian 116023, People’s Republic of

China

Hao Zheng − Dalian Institute of Chemical Physics, Chinese

Academy of Sciences, Dalian 116023, People’s Republic of

China; University of Chinese Academy of Sciences, Beijing

100049, People’s Republic of China

Gu-Cheng He − Dalian Institute of Chemical Physics, Chinese

Academy of Sciences, Dalian 116023, People’s Republic of

China; University of Chinese Academy of Sciences, Beijing

100049, People’s Republic of China

Heng Liu − Dalian Institute of Chemical Physics, Chinese

Academy of Sciences, Dalian 116023, People’s Republic of

China; University of Chinese Academy of Sciences, Beijing

100049, People’s Republic of China

Yan-Cheng Hu − Dalian Institute of Chemical Physics,

Chinese Academy of Sciences, Dalian 116023, People ’s

Republic of China; orcid.org/0000-0002-8731-4445

Complete contact information is available at:

https://pubs.acs.org/10.1021/acscatal.1c01488

ASSOCIATED CONTENT

sı Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acscatal.1c01488.

■

Notes

The authors declare no competing ﬁnancial interest.

Experimental procedures, characterization data, and

NMR spectra (PDF)

ACKNOWLEDGMENTS

■

(

We thank Prof. Yong-Gui Zhou (DICP), Prof. Vy M. Dong

UC Irvine), and Prof. Zhi-Shi Ye (DUT) for helpful

discussions and manuscript revisions. Financial support from

Dalian Institute of Chemical Physics (DICPI201902), Dalian

Outstanding Young Scientiﬁc Talent, and the National Natural

Science Foundation of China (22071239, 21801239) is

acknowledged.

AUTHOR INFORMATION

■

Corresponding Author

Qing-An Chen − Dalian Institute of Chemical Physics,

Chinese Academy of Sciences, Dalian 116023, People’s

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REFERENCES

Gonzalez, S.; Marion, N.; Nolan, S. P. N-Heterocyclic Carbenes in

Research Article

S. A.; Slatford, P. A.; Williams, J. M. J. Borrowing Hydrogen in the

Activation of Alcohols. Adv. Synth. Catal. 2007 , 349 , 1555. (c) Diez-

Late Transition Metal Catalysis. Chem. Rev. 2009, 109 , 3612.

■

(1) (a) Schafer, F. Q.; Buettner, G. R. Redox Environment of the

Cell as Viewed through the Redox State of the Glutathione Disulfide/

Glutathione Couple. Free Radical Biol. Med. 2001, 30, 1191.

(d) Nixon, T. D.; Whittlesey, M. K.; Williams, J. M. J. Transition

(

b) Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M. T. D.; Mazur,

Metal Catalysed Reactions of Alcohols Using Borrowing Hydrogen

Methodology. Dalton Trans 2009 , 753. (e) Rigoli, J. W.; Moyer, S. A.;

Pearce, S. D.; Schomaker, J. M. alpha,beta-Unsaturated imines via Ru-

catalyzed coupling of allylic alcohols and amines. Org. Biomol. Chem.

M.; Telser, J. Free Radicals and Antioxidants in Normal Physiological

Functions and Human Disease. Int. J. Biochem. Cell Biol. 2007 , 39 , 44.

c) Murphy, M. P. How Mitochondria Produce Reactive Oxygen

Species. Biochem. J. 2009, 417, 1.

2) (a) Rice-Evans, C.; Spencer, J. P.; Schroeter, H.; Rechner, A. R.

012, 10, 1746. (f) Dai, W.; Chalkley, M. J.; Brudvig, G. W.; Hazari,

N.; Melvin, P. R.; Pokhrel, R.; Takase, M. K. Synthesis and Properties

of NHC-Supported Palladium(I) Dimers with Bridging Allyl,

Cyclopentadienyl, and Indenyl Ligands. Organometallics 2013 , 32 ,

Bioavailability of Flavonoids and Potential Bioactive Forms in Vivo.

Drug Metab. Drug Interact. 2000 , 17 , 291. (b) Ge, Z.; Liu, S.

Functional Block Copolymer Assemblies Responsive to Tumor and

Intracellular Microenvironments for Site-Specific Drug Delivery and

Enhanced Imaging Performance. Chem. Soc. Rev. 2013 , 42 , 7289.

114. (g) Gumrukcu, Y.; de Bruin, B.; Reek, J. N. Dehydrative Cross-

Coupling Reactions of Allylic Alcohols with Olefins. Chem. - Eur. J.

014 , 20 , 10905. (h) Emayavaramban, B.; Roy, M.; Sundararaju, B.

c) Nishida, M.; Toyama, T.; Akaike, T. Role of 8-Nitro-Cgmp and

Iron-Catalyzed Allylic Amination Directly from Allylic Alcohols.

Chem. - Eur. J. 2016 , 22 , 3952. (l) Kumar, G. S.; Singh, D.; Kumar,

M.; Kapur, M. Palladium-Catalyzed Aerobic Oxidative Coupling of

Allylic Alcohols with Anilines in the Synthesis of Nitrogen

Heterocycles. J. Org. Chem. 2018 , 83 , 3941. (m) Corma, A.; Navas,

J.; Sabater, M. J. Advances in One-Pot Synthesis through Borrowing

Hydrogen Catalysis. Chem. Rev. 2018 , 118 , 1410. (n) Irrgang, T.;

Kempe, R. 3d-Metal Catalyzed N- and C-Alkylation Reactions via

Borrowing Hydrogen or Hydrogen Autotransfer. Chem. Rev. 2019,

Its Redox Regulation in Cardiovascular Electrophilic Signaling. J. Mol.

Cell. Cardiol. 2014, 73, 10. (d) Luca, S. V.; Macovei, I.; Bujor, A.;

Miron, A.; Skalicka-Wozniak, K.; Aprotosoaie, A. C.; Trifan, A.

Bioactivity of Dietary Polyphenols: The Role of Metabolites. Crit. Rev.

Food Sci. Nutr. 2020, 60, 626.

(3) (a) Noell, W. K.; Albrecht, R. Irreversible Effects of Visible Light

on Retina: Role of Vitamin A. Science 1971, 172, 76. (b) Béja, O.;

Aravind, L.; Koonin, E. V.; Suzuki, M. T.; Hadd, A.; Nguyen, L. P.;

Jovanovich, S.; Gates, C. M.; Feldman, R. A.; Spudich, J. L.; Spudich,

E. N.; DeLong, E. F. Bacterial Rhodopsin: Evidence for a New Type

of Phototrophy in the Sea. Science 2000, 289, 1902. (c) Palczewski, K.

Chemistry and Biology of Vision. J. Biol. Chem. 2012, 287, 1612.

19 , 2524. (o) Najera, C.; Foubelo, F.; Sansano, J. M.; Yus, M.

Stereodivergent routes in organic synthesis: carbohydrates, amino

acids, alkaloids and terpenes. Org. Biomol. Chem. 2020, 18, 1232.

(8) (a) Nguyen, K. D.; Park, B. Y.; Luong, T.; Sato, H.; Garza, V. J.;

(d) Wang, W.; Nossoni, Z.; Berbasova, T.; Watson, C. T.; Yapici, I.;

Krische, M. J. Metal-Catalyzed Reductive Coupling of Olefin-Derived

Nucleophiles: Reinventing Carbonyl Addition. Science 2016, 354,

aah5133. (b) Zhang, Z.-J.; Tao, Z.-L.; Arafate, A.; Gong, L.-Z.

Asymmetric Carbonyl Allylation of Aldehydes with Allylic Alcohols

under the Sequential Catalysis of Palladium Complex and Chiral

Phosphoric Acid. Huaxue Xuebao 2017, 75, 1196. (c) Fan, L.-F.; Luo,

S.-W.; Chen, S.-S.; Wang, T.-C.; Wang, P.-S.; Gong, L.-Z. Nucleophile

Coordination Enabled Regioselectivity in Palladium-Catalyzed

Asymmetric Allylic C-H Alkylation. Angew. Chem., Int. Ed. 2019, 58,

Lee, K. S. S.; Vasileiou, C.; Geiger, J. H.; Borhan, B. Tuning the

Electronic Absorption of Protein-Embedded All-trans -Retinal. Science

5) Yeum, K. J.; Ferreira, A. L. D.; Smith, D.; Krinsky, N. I.; Russell,

012, 338, 1340.

4) Bok, D. The Retinal-Pigment Epithelium - a Versatile Partner in

Vision. J. Cell Sci. 1993, 1993, 189.

(

R. M. The Effect of α -Tocopherol on the Oxidative Cleavage of β -

Carotene. Free Radical Biol. Med. 2000, 29, 105.

in Organic Synthesis. Angew. Chem., Int. Ed. 2009 , 48 , 2854.

6) (a) Burns, N. Z.; Baran, P. S.; Hoffmann, R. W. Redox Economy

b) Chen, K.; Baran, P. S. Total Synthesis of Eudesmane Terpenes

by Site-Selective C-H Oxidations. Nature 2009 , 459 , 824.

c) Dobereiner, G. E.; Crabtree, R. H. Dehydrogenation as a

16806. (d) Shen, H.-C.; Zhang, L.; Chen, S.-S.; Feng, J.; Zhang, B.-

W.; Zhang, Y.; Zhang, X.; Wu, Y.-D.; Gong, L.-Z. Enantioselective

Addition of Cyclic Ketones to Unactivated Alkenes Enabled by

Amine/Pd(II) Cooperative Catalysis. ACS Catal. 2019, 9, 791.

(e) Wang, T.-C.; Fan, L.-F.; Shen, Y.; Wang, P.-S.; Gong, L.-Z.

Substrate-Activating Strategy in Homogeneous Transition-Metal

Catalysis. Chem. Rev. 2010 , 110 , 681. (d) Morris, R. H. Exploiting

Metal-Ligand Bifunctional Reactions in the Design of Iron

Asymmetric Hydrogenation Catalysts. Acc. Chem. Res. 2015 , 48 ,

Asymmetric Allylic C-H Alkylation of Allyl Ethers with 2-

Acylimidazoles. J. Am. Chem. Soc. 2019 , 141 , 10616. (f) Wang, Y.;

Zhang, W.-Y.; You, S.-L. Ketones and Aldehydes as O-Nucleophiles in

Iridium-Catalyzed Intramolecular Asymmetric Allylic Substitution

Reaction. J. Am. Chem. Soc. 2019 , 141 , 2228. (g) Zhang, H.-J.; Yang,

Z.-P.; Gu, Q.; You, S.-L. Tandem Pd-Catalyzed Intermolecular Allylic

Alkylation/Allylic Dearomatization Reaction of Benzoylmethyl

Pyridines, Pyrazines, and Quinolines. Org. Lett. 2019 , 21 , 3314.

(9) (a) Trost, B. M. α -Sulfenylated Carbonyl-Compounds in

Organic-Synthesis. Chem. Rev. 1978, 78, 363. (b) Otera, J. Modern

Carbonyl Chemistry; Wiley-VCH, 2000; p 33. (c) Brachmachari, G.

Bioactive Natural Products ; CRC Pr I Llc, 2007; p 1. (d) Bellina, F.;

Rossi, R. Transition Metal-Catalyzed Direct Arylation of Substrates

494. (e) Zell, T.; Milstein, D. Hydrogenation and Dehydrogenation

Iron Pincer Catalysts Capable of Metal Ligand Cooperation by

Aromatization/Dearomatization. Acc. Chem. Res. 2015, 48, 1979.

f) Belkova, N. V.; Epstein, L. M.; Filippov, O. A.; Shubina, E. S.

Hydrogen and Dihydrogen Bonds in the Reactions of Metal Hydrides.

Chem. Rev. 2016 , 116 , 8545. (g) Hameury, S.; de Fremont, P.;

Braunstein, P. Metal Complexes with Oxygen-Functionalized Nhc

Ligands: Synthesis and Applications. Chem. Soc. Rev. 2017 , 46 , 632.

(h) Kallmeier, F.; Kempe, R. Manganese Complexes for (De)-

Hydrogenation Catalysis: A Comparison to Cobalt and Iron Catalysts.

Angew. Chem., Int. Ed. 2018, 57, 46. (i) Sordakis, K.; Tang, C.; Vogt,

L. K.; Junge, H.; Dyson, P. J.; Beller, M.; Laurenczy, G. Homogeneous

Catalysis for Sustainable Hydrogen Storage in Formic Acid and

Alcohols. Chem. Rev. 2018 , 118 , 372. (j) Alig, L.; Fritz, M.; Schneider,

S. First-Row Transition Metal (De)Hydrogenation Catalysis Based on

Functional Pincer Ligands. Chem. Rev. 2019, 119, 2681. (k) Varlet, T.;

Gelis, C.; Retailleau, P.; Bernadat, G.; Neuville, L.; Masson, G.

Enantioselective Redox-Divergent Chiral Phosphoric Acid Catalyzed

Quinone Diels-Alder Reactions. Angew. Chem., Int. Ed. 2020, 59,

with Activated sp -Hybridized C-H Bonds and Some of Their

Synthetic Equivalents with Aryl Halides and Pseudohalides. Chem.

Rev. 2010 , 110 , 1082. (e) Guillena, G.; Ramon, D. J. Recent Advances

on the Organocatalyzed Enantioselective α -Heterofunctionalization of

Carbonyl Compounds. Curr. Org. Chem. 2011 , 15 , 296. (f) Smith, A.

M. R.; Hii, K. K. Transition Metal Catalyzed Enantioselective α -

Heterofunctionalization of Carbonyl Compounds. Chem. Rev. 2011,

111, 1637.

(10) Top 200 Drugs by Retail Sales in 2019 by Njardarson Group .

https://njardarson.lab.arizona.edu/content/top-pharmaceuticals-

poster .

7) (a) Guillena, G.; Ramon, D. J.; Yus, M. Alcohols as Electrophiles

491.

in C −C Bond-Forming Reactions: The Hydrogen Autotransfer

Process. Angew. Chem., Int. Ed. 2007, 46, 2358. (b) Hamid, M. H.

(11) (a) Tsuji, J.; Minami, I. New Synthetic Reactions of Allyl Alkyl

Carbonates, Allyl Beta-Keto Carboxylates, and Allyl Vinylic

832

ACS Catal. 2021, 11, 6825−6834

ACS Catalysis

Carbonates Catalyzed by Palladium Complexes. Acc. Chem. Res. 1987 ,

Research Article

0 , 140. (b) Trost, B. M.; VanVranken, D. L. Asymmetric Transition

Metal-Catalyzed Allylic Alkylations. Chem. Rev. 1996, 96, 395.

c) Johannsen, M.; Jorgensen, K. A. Allylic Amination. Chem. Rev.

998 , 98 , 1689. (d) Trost, B. M.; Crawley, M. L. Asymmetric

Transition-Metal-Catalyzed Allylic Alkylations: Applications in Total

Synthesis. Chem. Rev. 2003, 103, 2921. (e) Helmchen, G.; Dahnz, A.;

Duebon, P.; Schelwies, M.; Weihofen, R. Iridium-Catalysed

Asymmetric Allylic Substitutions. Chem. Commun. 2007 , 675.

Surmiak, S.; Weiss, M.; Eckert, H.; Studer, A. Bifunctional

Mesoporous Silica Nanoparticles as Cooperative Catalysts for the

Tsuji-Trost Reaction - Tuning the Reactivity of Silica Nanoparticles.

Chem. Commun. 2013, 49 , 2195. (e) Wang, W.; Shen, H.; Wan, X.-L.;

Chen, Q.-Y.; Guo, Y. Enantioselective Pd-Catalyzed Allylation of

Acyclic α -Fluorinated Ketones. J. Org. Chem. 2014, 79, 6347.

(f) Zhao, Q.; Zhu, Y.; Sun, Z.; Li, Y.; Zhang, G.; Zhang, F.; Fan, X.

Combining Palladium Complex and Organic Amine on Graphene

Oxide for Promoted Tsuji-Trost Allylation. J. Mater. Chem. A 2015, 3,

2609. (g) Wang, Y.; Chai, J.; You, C.; Zhang, J.; Mi, X.; Zhang, L.;

Luo, S. Pi-Coordinating Chiral Primary Amine/Palladium Synergistic

Catalysis for Asymmetric Allylic Alkylation. J. Am. Chem. Soc. 2020,

142, 3184.

(15) (a) Trost, B. M.; Schroeder, G. M. Palladium-Catalyzed

Asymmetric Allylic Alkylation of Ketone Enolates. Chem. - Eur. J.

2005 , 11 , 174. (b) Kihara, N.; Motoda, S.; Yokozawa, T.; Takata, T.

End-Cap Exchange of Rotaxane by the Tsuji-Trost Allylation

Reaction. Org. Lett. 2005 , 7 , 1199. (c) Yoshida, M.; Terumine, T.;

Masaki, E.; Hara, S. Direct Asymmetric α -Allylation of α -Branched

Aldehydes by Two Catalytic Systems with an Achiral Pd Complex and

a Chiral Primary α -Amino Acid. J. Org. Chem. 2013, 78, 10853.

(d) Llevot, A.; Monney, B.; Sehlinger, A.; Behrens, S.; Meier, M. A. R.

Highly Efficient Tsuji-Trost Allylation in Water Catalyzed by Pd-

Nanoparticles. Chem. Commun. 2017, 53, 5175.

(

f) Lu, Z.; Ma, S. Metal-Catalyzed Enantioselective Allylation in

Asymmetric Synthesis. Angew. Chem., Int. Ed. 2008 , 47 , 258.

g) Hartwig, J. F.; Stanley, L. M. Mechanistically Driven Development

Res. 2010 , 43 , 1461. (h) Trost, B. M.; Zhang, T.; Sieber, J. D.

of Iridium Catalysts for Asymmetric Allylic Substitution. Acc. Chem.

Catalytic Asymmetric Allylic Alkylation Employing Heteroatom

Nucleophiles: A Powerful Method for C-X Bond Formation. Chem.

Sci. 2010 , 1 , 427. (i) Weaver, J. D.; Recio, A.; Grenning, A. J.; Tunge,

J. A. Transition Metal-Catalyzed Decarboxylative Allylation and

Benzylation Reactions. Chem. Rev. 2011, 111 , 1846. (j) Poli, G.;

Prestat, G.; Liron, F.; Kammerer-Pentier, C. Allylic Substitutions

Catalyzed by Miscellaneous Metals. Top. Organomet. Chem. 2011 , 38 ,

1. (k) Milhau, L.; Guiry, P. J. Iridium-Catalyzed Asymmetric Allylic

Substitutions. Top. Organomet. Chem. 2011 , 38 , 95. (l) Liu, W.-B.;

Xia, J.-B.; You, S.-L. Palladium-Catalyzed Enantioselective Allylic

Substitution. Top. Organomet. Chem. 2011, 38, 155. (m) Begouin, J.-

M.; Klein, J. E. M. N.; Weickmann, D.; Plietker, B. Selectivity in

Palladium-Catalyzed Allylic Substitution. Top. Organomet. Chem.

(16) Huo, X.; Quan, M.; Yang, G.; Zhao, X.; Liu, D.; Liu, Y.; Zhang,

W. Hydrogen-Bond-Activated Palladium-Catalyzed Allylic Alkylation

via Allylic Alkyl Ethers: Challenging Leaving Groups. Org. Lett. 2014,

16, 1570.

011 , 38 , 269. (n) Koschker, P.; Breit, B. Branching Out:

Rhodium-Catalyzed Allylation with Alkynes and Allenes. Acc. Chem.

Res. 2016 , 49 , 1524. (o) Feng, J.; Holmes, M.; Krische, M. J. Acyclic

Quaternary Carbon Stereocenters Via Enantioselective Transition

Metal Catalysis. Chem. Rev. 2017 , 117 , 12564. (p) Fu, J.; Huo, X.; Li,

B.; Zhang, W. Cooperative Bimetallic Catalysis in Asymmetric Allylic

Substitution. Org. Biomol. Chem. 2017 , 15 , 9747. (q) Haydl, A. M.;

Breit, B.; Liang, T.; Krische, M. J. Alkynes as Electrophilic or

Nucleophilic Allylmetal Precursors in Transition-Metal Catalysis.

Angew. Chem., Int. Ed. 2017 , 56 , 11312. (r) Holmes, M.; Schwartz, L.

A.; Krische, M. J. Intermolecular Metal-Catalyzed Reductive Coupling

of Dienes, Allenes, and Enynes with Carbonyl Compounds and

Imines. Chem. Rev. 2018, 118, 6026.

(17) (a) Kimura, M.; Horino, Y.; Mukai, R.; Tanaka, S.; Tamaru, Y.

Strikingly Simple Direct α -Allylation of Aldehydes with Allyl

Alcohols: Remarkable Advance in the Tsuji-Trost Reaction. J. Am.

Chem. Soc. 2001 , 123 , 10401. (b) Usui, I.; Schmidt, S.; Breit, B. Dual

Palladium- and Proline-Catalyzed Allylic Alkylation of Enolizable

Ketones and Aldehydes with Allylic Alcohols. Org. Lett. 2009, 11,

1453. (c) Huo, X.; Yang, G.; Liu, D.; Liu, Y.; Gridnev, I. D.; Zhang,

W. Palladium-Catalyzed Allylic Alkylation of Simple Ketones with

Allylic Alcohols and Its Mechanistic Study. Angew. Chem., Int. Ed.

2014 , 53 , 6776. (d) Pupo, G.; Properzi, R.; List, B. Asymmetric

Catalysis with CO : The Direct α -Allylation of Ketones. Angew.

Chem., Int. Ed. 2016 , 55 , 6099. (e) Liu, J.; Mishra, S.; Aponick, A.

Enol Acetates: Versatile Substrates for the Enantioselective Inter-

molecular Tsuji Allylation. J. Am. Chem. Soc. 2018, 140 , 16152.

(18) (a) Beletskaya, I. P.; Najera, C.; Yus, M. Stereodivergent

Catalysis. Chem. Rev. 2018 , 118 , 5080. (b) Najera, C.; Beletskaya, I.

P.; Yus, M. Metal-Catalyzed Regiodivergent Organic Reactions. Chem.

Soc. Rev. 2019 , 48 , 4515. (c) Beletskaya, I. P.; Najera, C.; Yus, M.

Chemodivergent Reactions. Chem. Soc. Rev. 2020, 49, 7101.

(12) (a) Aoyagi, K.; Nakamura, H.; Yamamoto, Y. Palladium-

Catalyzed Aminoallylation of Activated Olefins with Allylic Halides

and Phthalimide. J. Org. Chem. 2002 , 67 , 5977. (b) Reeves, C. M.;

Behenna, D. C.; Stoltz, B. M. Development of (Trimethylsilyl)ethyl

Ester Protected Enolates and Applications in Palladium-Catalyzed

Enantioselective Allylic Alkylation: Intermolecular Cross-Coupling of

Functionalized Electrophiles. Org. Lett. 2014 , 16 , 2314. (c) Wu, G. J.;

Zhang, Y. H.; Tan, D. X.; Han, F. S. Total Synthesis of Cyrneines A-B

and Glaucopine C. Nat. Commun. 2018, 9, 2148.

(19) (a) Kwon, M. S.; Kim, N.; Seo, S. H.; Park, I. S.; Cheedrala, R.

K.; Park, J. Recyclable Palladium Catalyst for Highly Selective α -

Alkylation of Ketones with Alcohols. Angew. Chem., Int. Ed. 2005, 44,

6913. (b) Anbarasan, P.; Baer, Z. C.; Sreekumar, S.; Gross, E.; Binder,

J. B.; Blanch, H. W.; Clark, D. S.; Toste, F. D. Integration of Chemical

Catalysis with Extractive Fermentation to Produce Fuels. Nature

2012, 491, 235. (c) Jorgensen, L.; McKerrall, S. J.; Kuttruff, C. A.;

Ungeheuer, F.; Felding, J.; Baran, P. S. 14-Step Synthesis of

(+)-Ingenol from (+)-3-Carene. Science 2013, 341, 878. (d) Xu, G.;

Li, Q.; Feng, J.; Liu, Q.; Zhang, Z.; Wang, X.; Zhang, X.; Mu, X.

Direct α -Alkylation of Ketones with Alcohols in Water. ChemSusChem

2014 , 7 , 105. (e) Yang, Q.; Wang, Q.; Yu, Z. Substitution of Alcohols

by N-Nucleophiles via Transition Metal-Catalyzed Dehydrogenation.

Chem. Soc. Rev. 2015, 44, 2305. (f) Baer, Z. C.; Bormann, S.;

Sreekumar, S.; Grippo, A.; Toste, F. D.; Blanch, H. W.; Clark, D. S.

Co-Production of Acetone and Ethanol with Molar Ratio Control

Enables Production of Improved Gasoline or Jet Fuel Blends.

Biotechnol. Bioeng. 2016 , 113 , 2079. (g) Lin, L.; Romano, C.;

Mazet, C. Palladium-Catalyzed Long-Range Deconjugative Isomer-

ization of Highly Substituted α ,β -Unsaturated Carbonyl Compounds.

J. Am. Chem. Soc. 2016 , 138 , 10344. (h) Jiang, L.; Guo, F.; Shi, Z.; Li,

Y.; Hou, Z. Syndiotactic Poly(Aminostyrene)-Supported Palladium

(13) (a) 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. (b) Xu, Y. N.; Zhu,

M. Z.; Tian, S. K. Chiral α -Amino Acid/Palladium-Catalyzed

Asymmetric Allylation of α -Branched β -Ketoesters with Allylic

Amines: Highly Enantioselective Construction of All-Carbon

Quaternary Stereocenters. J. Org. Chem. 2019 , 84 , 14936.

14) (a) You, S. L.; Dai, L. X. Enantioselective Palladium-Catalyzed

Decarboxylative Allylic Alkylations. Angew. Chem., Int. Ed. 2006, 45,

246. (b) Keith, J. A.; Behenna, D. C.; Mohr, J. T.; Ma, S.; Marinescu,

S. C.; Oxgaard, J.; Stoltz, B. M.; Goddard, W. A., III The Inner-Sphere

Process in the Enantioselective Tsuji Allylation Reaction with (S )-t -

Bu-Phosphinooxazoline Ligands. J. Am. Chem. Soc. 2007, 129, 11876.

Marinescu, S. C.; Nielsen, R. J.; Oxgaard, J.; Stoltz, B. M.; Goddard,

W. A., III The Reaction Mechanism of the Enantioselective Tsuji

Allylation: Inner-Sphere and Outer-Sphere Pathways, Internal

Rearrangements, and Asymmetric C-C Bond Formation. J. Am.

Chem. Soc. 2012, 134, 19050. (d) Dickschat, A. T.; Behrends, F.;

833

ACS Catal. 2021, 11, 6825−6834

ACS Catalysis

, 3827. (i) Kanda, Y.; Ishihara, Y.; Wilde, N. C.; Baran, P. S. Two-

Research Article

Catalyst for Ketone Methylation with Methanol. ChemCatChem 2017 ,

Phase Total Synthesis of Taxanes: Tactics and Strategies. J. Org.

Chem. 2020, 85, 10293.

20) (a) Chen, Q. A.; Kim, D. K.; Dong, V. M. Regioselective

Hydroacylation of 1,3-Dienes by Cobalt Catalysis. J. Am. Chem. Soc.

014, 136, 3772. (b) Hu, Y. C.; Ji, D. W.; Zhao, C. Y.; Zheng, H.;

Chen, Q. A. Catalytic Prenylation and Reverse Prenylation of Indoles

with Isoprene: Regioselectivity Manipulation through Choice of Metal

Hydride. Angew. Chem., Int. Ed. 2019, 58, 5438. (c) Ji, D. W.; Hu, Y.

C.; Zheng, H.; Zhao, C. Y.; Chen, Q. A.; Dong, V. M. A

Regioselectivity Switch in Pd-Catalyzed Hydroallylation of Alkynes.

Chem. Sci. 2019, 10, 6311. (d) Li, Y.; Hu, Y.-C.; Zheng, H.; Ji, D.-W.;

Cong, Y.-F.; Chen, Q.-A. Acid-Catalyzed Regiodivergent Annulation

of 4-Hydroxycoumarins with Isoprene: Entry to Pyranocoumarins and

Pyranochromones. Eur. J. Org. Chem. 2019, 2019, 6510. (e) Yang, J.;

Ji, D. W.; Hu, Y. C.; Min, X. T.; Zhou, X.; Chen, Q. A. Cobalt-

Catalyzed Hydroxymethylarylation of Terpenes with Formaldehyde

and Arenes. Chem. Sci. 2019, 10, 9560. (f) Ji, D.-W.; He, G.-C.;

Zhang, W.-S.; Zhao, C.-Y.; Hu, Y.-C.; Chen, Q.-A. Nickel-Catalyzed

Allyl −Allyl Coupling Reactions between 1,3-Dienes and Allylboro-

nates. Chem. Commun. 2020, 56, 7431. (g) Kuai, C. S.; Ji, D. W.;

Zhao, C. Y.; Liu, H.; Hu, Y. C.; Chen, Q. A. Ligand-Regulated

Regiodivergent Hydrosilylation of Isoprene under Iron Catalysis.

Angew. Chem., Int. Ed. 2020, 59, 19115. (h) Li, Y.; Hu, Y.-C.; Ji, D.-

W.; Zhang, W.-S.; He, G.-C.; Cong, Y.-F.; Chen, Q.-A. Acid-Catalyzed

Chemoselective C - and O - Prenylation of Cyclic 1,3-Diketones. Chin.

J. Catal. 2020, 41, 1401.

(21) (a) The oxidative coupling was completely suppressed under

hydrogen atmosphere. (b) With the N gas blown into the system

during the reductive coupling, the yield of 3a decreased to 12%.

22) Hong, B.-C.; Wu, M.-F.; Tseng, H.-C.; Liao, J.-H.

Enantioselective Organocatalytic Formal 3 + 3-Cycloaddition of

α ,β -Unsaturated Aldehydes and Application to the Asymmetric

Synthesis of (−)-Isopulegol Hydrate and (−)-Cubebaol. Org. Lett.

2006, 8, 2217.

834