Visible-Light-Driven Transformations of Phenols via Energy ...€¦ · 2 Intermolecular Processes 2.1 Reactions with Singlet Oxygen 2.2 [2+2] Cycloadditions 3 Intramolecular Transformations

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J. Fischer et al. Short ReviewSyn thesis

SYNTHESIS0 0 3 9 - 7 8 8 1 1 4 3 7 - 2 1 0 X© Georg Thieme Verlag Stuttgart · New York2020, 52, 1617–1624short reviewen

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Visible-Light-Driven Transformations of Phenols via Energy Transfer CatalysisJérôme Fischer Pierrick Nun Vincent Coeffard* 0000-0003-2982-7880

Université de Nantes, CEISAM UMR CNRS 6230, 44000 Nantes, [email protected]

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Received: 28.11.2019Accepted after revision: 26.02.2020Published online: 02.04.2020DOI: 10.1055/s-0039-1708005; Art ID: ss-2019-z0654-sr
Abstract In the past decade, the field of visible-light-mediated photo-catalysis has been particularly thriving by offering innovative synthetictools for the construction of functionalized architectures from simpleand readily available substrates. One strategy that has been of interestis energy transfer catalysis, which is a powerful way of activating a sub-strate or an intermediate by using the combination of light and a rele-vant photosensitizer. This review deals with recent advances in energytransfer catalysis applied to phenols, which are ubiquitous in chemistryboth as starting materials and as high-added-value products. Processesinvolving energy transfer from the excited photosensitizer to groundstate oxygen and to phenol-containing substrates will be described.1 Introduction2 Intermolecular Processes2.1 Reactions with Singlet Oxygen2.2 [2+2] Cycloadditions3 Intramolecular Transformations4 Conclusions and Outlook

Key words photochemistry, phenol, dearomatization, cycloaddition,singlet oxygen

1 Introduction

The concept of harnessing visible light to trigger chemi-cal transformations is a powerful tool in organic chemistry.1Nevertheless, most of the organic compounds do not pos-sess the relevant absorption features for a direct photoexci-tation strategy under visible light.2 Within this context, vis-ible-light-mediated photocatalysis has significantly con-tributed to the advent of photochemistry by enabling thereaction of photoexcited species with organic moleculesthrough electron, atom or energy transfer processes. Whileenormous achievements have been made in photo-initiatedelectron transfer catalytic processes (photoredox cataly-sis),3 the field of energy transfer catalysis (EnT) has compar-

atively received less attention. Energy transfer catalysis in-volves the combination of a photosensitizer (PS), a sub-strate (S), and light.4 This photochemical process is basedon the deactivation of an excited-light absorbing sensitizer(PS*) by transferring its energy to a substrate S leading tothe formation of the excited substrate S* (Figure 1). Unlikephotoredox catalysis, no single-electron transfer occurs be-tween the excited photocatalyst and the substrate or anyintermediates from the reaction mixture.

Figure 1 Energy transfer and photoredox catalysis

Breakthroughs in energy transfer catalysis have beendriven by the design of new photosensitizers and the im-plementation of innovative synthetic transformations withapplications in a range of contexts.5 By careful examinationof the reaction conditions, visible-light-induced energytransfer catalysis has been harnessed in a series of transfor-mations such as [2+2] photocycloadditions, alkene pho-toisomerizations, sensitization of metal complexes, oxida-tive processes through the formation of singlet oxygen, orthe activation of azide and diazo compounds to form het-erocyclic compounds.4 Amongst the substrates tested, phe-nol derivatives were deemed worthy of investigation be-cause of their unique chemical behavior. Besides classicalreactivities such as electrophilic aromatic substitutions6

and C–O bond forming reactions,7 considerable attentionhas been given in recent years to dearomatization process-es8 and direct C–H functionalizations of the aromatic ring.9

© 2020. Thieme. All rights reserved. Synthesis 2020, 52, 1617–1624Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

http://orcid.org/0000-0003-2982-7880

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In addition, recent advances regarding valorization of bio-mass to produce phenols have made these compounds at-tractive platforms in organic chemistry.10 The manifold re-activity of phenols with the synthetic appeal of energytransfer catalysis offers a powerful strategy to reach novelmolecular architectures (Figure 2). This is the subject of thisreview, which does not intend to be comprehensive, butrather to point out the synthetic potential and future chal-lenges of this methodology.

2 Intermolecular Processes

In intermolecular transformations, the reaction can beinitiated by energy transfer from the excited triplet photo-sensitizer to the phenol-containing substrate or the reac-tant such as ground state triplet oxygen (3O2) leading to the

formation of the highly electrophilic species singlet oxygen(1O2). The two strategies will be discussed in the followingexamples.

2.1 Reactions with Singlet Oxygen

For many decades now, it has been demonstrated thatsinglet oxygen (1O2) is a powerful reactant toward electron-rich substrates.11 An energy of 94 kJ·mol–1 is required toform the highly electrophilic singlet oxygen from groundstate oxygen. Many photosensitizers (tetraphenylporphy-rin, rose bengal, methylene blue to cite only a few) possess atriplet energy (ET) equal or greater than 94 kJ·mol–1 re-quired to efficiently sensitize triplet oxygen into its singletstate. In synthetic chemistry, electron-rich phenols areprone to react with singlet oxygen and this research fieldhas received considerable attention from a mechanistic andsynthetic point of view.

In 2019, Dlugogorski and co-workers reported a mecha-nistic and kinetic study on the photooxygenation of phenol(Scheme 1, R = H).12 Based on DFT calculations and electronparamagnetic resonance (EPR), their results provided evi-dence for the 1,4-endoperoxide intermediate, obtained af-ter a [4+2] cycloaddition, yielding p-benzoquinone as theonly detected product after ring opening. Indeed, the 1,4-

Vincent Coeffard (left) was born in Nantes (France) in 1981. He stud-ied chemistry at Université de Nantes and completed his Ph.D. studies in 2007 in the group of Prof. Jean-Paul Quintard. He then moved to Uni-versity College Dublin (Ireland) to work as a postdoctoral research fel-low for two years in asymmetric catalysis under the guidance of Prof. Pat Guiry. He then spent ten months in Spain for a second postdoctoral experience in the group of Prof. Antonio M. Echavarren to investigate gold chemistry. In 2010, he was appointed CNRS researcher in the group of Prof. Christine Greck at Université de Versailles Saint-Quentin-en-Yvelines (France) to work on the design of organocatalysts and im-plementation of catalytic technologies to access enantioenriched or-ganic architectures. In 2016, he moved to Université de Nantes where his current research interests include asymmetric organocatalysis and photochemistry.

Pierrick Nun (middle) was born in Brest (France) in 1982. After under-graduate studies at Université de Nantes (France), he completed his Ph.D. in 2009 under the supervision of Dr. Frédéric Lamaty at Université de Montpellier (France), working on mechanical activation and solvent-free synthesis. He then joined the group of Prof. Steven P. Nolan at the University of St. Andrews (Scotland) as a post-doctoral researcher. Fol-lowing a second post-doctoral fellowship with Prof. Annie-Claude Gaumont at the Ecole Nationale Superieure d’Ingenieurs of Caen (France), he was appointed Assistant Professor at Université de Nantes and he is currently working on singlet oxygen applications in organic synthesis and medicine.

Jérôme Fischer (right) was born in 1994 in Mulhouse (France). After fin-ishing his high school diploma, he studied chemistry at the Ecole Natio-nale Supérieure de Chimie of Mulhouse and joined the group of Dr. Vincent Coeffard for his Ph.D. studies in 2017. His research focuses on the design of new photosensitizers for applications in selective photoo-xidative processes.

Figure 2 Phenol transformations via energy transfer catalysis

OH

R1

R2EnT

dearomatization

[2+2] cycloaddition

cyclization

O

R1

R2

OHO

O

R1

R2 = O

Scheme 1 Singlet-oxygen-mediated oxidation of phenols

OH

1O2OH

OO

O

O

R

R

1,4-endoperoxide

R = H

– H2O

R = Alk,(Het)Ar

O

p-benzoquinone

R O2Hp-peroxy quinols

EnT3O2

© 2020. Thieme. All rights reserved. Synthesis 2020, 52, 1617–1624

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cycloaddition of 1O2 at the ipso- and para-positions requiresa 17–22 kJ·mol–1 lower energy barrier than the correspond-ing addition at the ortho and meta carbons.

When singlet oxygen reacts with para-substituted phe-nols, the in situ opening of the corresponding 1,4-endoper-oxides results in the formation of p-peroxy quinols, thatcould then be reduced smoothly with triphenylphosphineor dimethyl sulfide to give the corresponding alcohols.13

The photooxidative dearomatization of para-substitutedphenols with 1O2 led to highly oxygenated frameworks andwas subsequently applied as a key reaction in numerousmultistep reactions as these structures can be found inmany natural products. In this short review, we will focusour attention to the recent advances in 1O2-mediated dearo-matizations of para-substituted phenols.

As a first example, Kilic and co-workers prepared thehydroperoxides 2 after photooxygenation of the acetani-lides 1 towards their syntheses of epoxy quinol antibiotics(Scheme 2).14 This reaction was realized with tetraphenyl-porphyrin (TPP)15 as photosensitizer and no control on ste-reoselectivity was observed for this oxidation starting froma chiral substrate 1b.

Scheme 2 Photooxygenation of acetanilides

The hydroperoxides 2 were then reduced to the corre-sponding alcohols, which underwent a Weitz–Scheffer ep-oxidation with tert-butyl hydroperoxide (TBHP) leading tothe cis-epoxy quinols 3, important building blocks in Manu-mycin natural products (Scheme 3).

Oxidative dearomatization was also used by Hoye andco-workers in their synthesis of the polar pharmacophoricsubunit of (+)-scyphostatin.16 The singlet-oxygen-mediated

oxidation of 4 with rose bengal17 as photosensitizer underbasic conditions followed by reduction with Me2S wasfound as an efficient and atom economic alternative to aclassical phenyliodine diacetate oxidation (Scheme 4).

Scheme 4 Oxidative dearomatization of 4

Following these results, Klussmann and co-workers de-scribed in 2013 a sequence of peroxide formation, reduc-tion, and intramolecular cyclization of 6 to give access tooxaspirocycles 7 (Scheme 5).18 This sequence could be exe-

OHHN

Me

O

R

O2

TPP (0.8–1.4 mol%)visible light

O

Me O2H

HN

O

R

Photosensitizer

HN

N

NH

N

TPPtetraphenylporphyrin

ET = 140 kJ/molλabs = 300–700 nm

Methodology

Examples

O

Me O2H

HN

O

Me

2a, 62%

O

Me O2H

HN

O

Me

OAc

2b, 70%

acetone/CH2Cl2 or CHCl3

–25 °C or RT, 2 d1 2

Scheme 3 Synthesis of cis-epoxy quinols

O

Me O2H

HN

O

R

2a,b

O

Me OH

HN

O

R

3a (65%)3b (66%)

O

1) Me2S, Ti(Oi-Pr)4 CH2Cl2, RT, 1 h

2) TBHP, DBU CH2Cl2, RT

OH

TrocNO

MeMe

O2RB (10 mol%)

visible light

EtOH, pH 10 buffer0 °C, 3 h

then Me2S, 45%

O

OH

Photosensitizer

RBrose bengal


Methodology

4 5

O

Cl

Cl

Cl

Cl

CO2Na

I

O

I

I

I

ONa

TrocNO

MeMe

Scheme 5 Oxaspirocycles synthesis via a photooxygenation/reduc-tion/cyclization sequence

OH O2TPP, visible light

CHCl3, RT, 16–48 h

O

O2H

i) reduction

ii) cyclization

O

O

t-Bu t-Bu

O

O

O

O

O

O

O7a (74%, one pot) 7b (50%, one pot) 7c (72%)

Application

Methodology

n = 2, 3X = Cl, CO2Me, OCOMe

n n

X 76

O

O

X


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cuted stepwise or more conveniently in a one-pot fashion,without isolation of the hydroperoxide intermediates. Hereagain, the key oxidative dearomatization is an atom-eco-nomic alternative to hypervalent iodine reactants. Althoughthe scope is limited to 3 examples of oxaspirocyclic com-pounds 7, it demonstrated the potential of photosensitizeddearomatization of phenols to obtain more complex struc-tures.

Singlet-oxygen chemistry has been harnessed in totalsynthesis of natural and biologically relevant products.19

For instance, an elegant diastereoselective visible-light-in-duced oxidative dearomatization was observed by thegroup of Li during their synthesis of the tricyclic frameworkcontained in tiglianes and daphnanes (Scheme 6).20 UsingTPP as photosensitizer in chloroform under a strong visiblelight, irradiation followed by reduction of the correspond-ing p-peroxy quinol led to the alcohol 9 as a single diaste-reoisomer in a high yield (74%). The relative configurationwas established by X-ray diffraction analysis, and it was as-sumed that this stereoselectivity was due to the trimethyl-silyl ether moiety and its steric hindrance on one face of thephenol, leading singlet oxygen to react on the other face.

Scheme 6 Oxidative dearomatization towards the synthesis of tigliane and daphnane diterpenes

Another diastereoselective oxidative transformationwas conducted as a key step in the synthesis of erythrina al-kaloids by the group of Kitamura and Fukuyama (Scheme7).21 Here again, the steric hindrance around the phenol hasa strong influence on the stereoselective 1O2 addition. An X-ray analysis confirmed that the silyloxy group is pointingtoward the phenol moiety. This configuration and the atro-poisomeric stereochemistry guided singlet oxygen to reactspecifically on one face of 10 to give selectively a peroxidethat led to a spontaneous reaction with the amide nitrogenyielding efficiently 11 (77%) as a single diastereomer.

Inspired by these results, we reported in 2018 a one-potBodipy-catalyzed domino photooxygenation.22 A photosen-sitized singlet-oxygen-mediated phenol dearomatization,followed by a [4+2] cycloaddition gave a variety of six-membered-ring-fused furans 13 under mild conditions(Scheme 8). The best results were obtained by using thereadily available Bodipy PS1 as a photosensitizer.23 Startingfrom 2-alkenylphenols 12, we envisioned that a first singletoxygen molecule would react as previously described withthe more electron-rich phenol, giving the correspondinghydroperoxide A. A second singlet oxygen molecule couldthen react with these intermediates in a classical [4+2]

cycloaddition that would ultimately render the fused furans13 after reduction. Mechanistic studies were carried out tooutline the importance of singlet oxygen in the reactionoutcome.

OH

TMSO

H O2TPP (5 mol%),visible light

CHCl3, 0 °Cthen PPh3, 74%

O

TMSO

H

OH

8 9

Scheme 7 Multibond-forming process

OH

O

O TBSONH

O

O2RB (5 mol%)visible light

PPh3, NaHCO3MeCN/H2O (1:1), RT

77%

O

O

O TBSONH

O

OHO

O

O N O

OH

OTBS

O

10 11

Scheme 8 Catalyzed domino photooxygenation

OH

R1

R3

R2

O2PS1 (2 mol%)

xenon lightCDCl3, 10 °C, 6 h

then thiourea, MeOH16 h, 40 °C

O

R3

HO R1

OR2

O

HO Me

OPh

13a, 53%

O

HO Me

O4-MeC6H4

O

HO Me

O3-MeC6H4

13b, 50% 13c, 41%

O

HO Ph

OPh

13d, 35%

O

HO Me

O2,4-Cl2C6H3

O

HO Me

OPh

13e, 54%

Me

13f, 60%

O

R3

R2

R1HOO

O

R3

R1HOOO

O

R2

1O2

1O2

reduction

Photosensitizer

Selected examples

NB

NI

Me

Me

Ph Me

I

MeF F

PS1ET = 145 kJ/mol

λabs = 450–600 nm

Methodology

12 1313 examples

30–60%

A B


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Scheme 9 Epoxyquinol synthesis via photooxygenation under basic conditions

The importance of functionalized epoxyquinol frame-works in natural products served to challenge synthetic or-ganic chemists.24 Previous reports have shown that phenolswere interesting substrates to get access to epoxyquinolsthrough a 1O2-mediated dearomatization/reduction/epoxi-dation sequence (Schemes 2 and 3). Nevertheless, the re-duction/oxidation tactic lowers the synthetic appeal of thisstrategy. In order to harness the full potential of singlet ox-ygen by transferring both oxygen atoms, we reported a one-pot synthesis of cis-epoxyquinols 15 starting from phenols14 (Scheme 9).25 The key point for the success of the reac-tion lies in the use of basic conditions.

After optimization studies and mechanistic insights, wedemonstrated that using rose bengal as photosensitizer andcesium carbonate as base led to a large scope of functional-ized epoxyquinols. Cesium carbonate plays a pivotal role byincreasing the kinetic of the photooxygenation step whiletriggering the epoxidation reaction.

2.2 [2+2] Cycloadditions

A second class of reactions initiated by energy transfer is[2+2] cycloaddition reactions. Contrary to photoredoxstrategies, visible-light photocatalyzed [2+2] cycloadditionsby energy transfer are not limited by electrochemical po-tentials. This was demonstrated by the breakthrough workof Yoon and co-workers who developed a two-catalyststrategy for enantioselective cycloadditions of phenol de-rivatives 16.26 Indeed, scandium(III) salts in the presence ofa chiral ligand formed a chiral Lewis acid acting as a catalystfor inducing enantioselectivities (Scheme 10).27 A large di-

OH

R4 R1

R3

R2

O

R3

R4 R1

O

R2 OH

O2 RB (1 mol%)

Cs2CO3 (15 mol%)

green LED, MeOHRT, 3 h

O

O

Me OH

Ph

15a, 50%

O

O

Me OH

O

OEt

15b, 55%

OCO2Me

O

Me OH

15c, 46%

O

O

Et OH

Cl

15d, 70%

Methodology

Selected examples

Proposed mechanism

14

1517 examples

11–75%

OCs

Me

14a

PhCs2CO3

– CsHCO3 A

O

Ph

Me O2Cs

1O23O2

RB* RB

O

Ph

Me OO

Cs

O

Me OCs

O

Ph

14a

15a

B

C

D

Scheme 10 Enantioselective [2+2] cycloadditions through Lewis acid catalyzed triplet energy transfer

MLn

+

Ru(bpy)3(PF6)2 (2.5 mol%)L = (S,S)-t-Bu-PyBox

(15 mol%)M = Sc(OTf)3 (10 mol%)

i-PrOAc/MeCN (3:1) 23 W CFL, 20 h

OH O

Ar R1 R2

OH O

Ph Me Me

17a, 84%93% ee, 3:1 d.r.

OH O

Ph Me Me

17b, 86%83% ee, 2:1 d.r.

Me

OH O

Ph Me

17c, 92%84% ee, 3:1 d.r.

OH O

Me

17d, 82%85% ee, 4:1 d.r.

OH O

Me Me

17e, 72%93% ee, 3:1 d.r.

Methodology

Application: selected examples

Catalytic system

Ru2+

N

N

N

N N

N Ru(bpy)3


OH O

Ar

RR

R1

R2

R3

R3

1617

12 examples, 66–86%up to 4:1 d.r.83–98% ee

NO

N N

O

t-Bu t-Bu

(S,S)-t-Bu-PyBox

O

Br

EnT

coordination by the chiral Lewis acid (MLn)

*

A B

O O

Ar

R

MLn

O O

Ar

R

diene


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versity of asymmetric [2+2] cycloadditions was conductedon diversely substituted phenol derivatives 16 and dienes.

After mechanistic and computational investigations,they demonstrated that complexation of 16a with Sc(III)salts results in a dramatic decrease in the energy of thetriplet state, from ET(exp) = 54 kcal/mol to 32 kcal/mol. Noreaction occurred in the absence of any Lewis acid as wellas in the absence of light. The formation of the chiral com-plex A involving the Sc(III) salt, the chiral PyBox ligand, andthe two oxygens of the 2′-hydroxychalcone 16 is probablythe key intermediate, leading the [2+2] cycloaddition toproceed in an enantioselective way.

Very recently, Chen, Shen, and co-workers carried out adetailed computational study on the mechanism of thistransformation.28 Among many other data, they explainedthe origin of chirality in this reaction by energy changes inthe triplet state depending of the attacked side of the coor-dinated chalcone.

In a further study, the group of Yoon extended the scopeof the reaction to various styrenes and diene systems, ob-taining high enantiomeric excesses and giving a direct ac-cess to diarylcyclobutane natural products (Scheme 11).29

Following Yoon’s pioneering works, Feng, Liu and co-work-ers also reported an enantioselective [2+2] cycloadditioninvolving 2′-hydroxychalcones 16 (Scheme 12).30

Scheme 11 Photocycloadditions of olefins

Scheme 12 [2+2] Photocycloaddition mediated by N,N′-dioxide-metal complexes

Reaction conditions are quite similar but tetradentateN,N′-dioxide platforms were used to form a chiral clusterwith Sc(III). Results are comparable to those obtained byYoon in term of yields and enantiomeric excesses, but aregenerally better in term of diastereoselectivities, with ratiosup to 6.1:1.

3 Intramolecular Transformations

Although limited, intramolecular visible-light-photo-catalyzed transformations of phenols by energy transferhave already been reported. As highlighted in the previoussection, alkenes are prone to undergo [2+2] cycloadditionsby energy transfer catalysis. In 2012, the group of Yoon ex-plored the [2+2] photocycloaddition of alkenes 20 per-formed in the presence of 1 mol% of PS2 under visible light(Scheme 13, top).31 This transformation was applied to theexpedient synthesis of racemic cannabiorcicyclolic acid,which is a natural product belonging to the family of canna-binoids (Scheme 13, down). Condensation of the phenol 22and citral 23 gave rise to the cycloadduct precursor 24 in54% yield. The photocycloaddition was performed in thepresence of 1 mol% of PS2 in DMSO under visible light. After8 hours of irradiation, the desired cyclobutane-containingcompound 25 was isolated in 86% yield and subsequent hy-drolysis of the ester function afforded the natural productin 97% yield.

In previous examples, the energy transfer took place be-tween the reactants and the excited photosensitizers. Theconcept of energy transfer catalysis has been also applied totransition metal complexes providing a wealth of untappedsynthetic potential in organometallic chemistry.32 This

+

Ru(bpy)3(PF6)2 (2.5 mol%)(S,S)-t-Bu-PyBox

(15 mol%)Sc(OTf)3 (10 mol%)

i-PrOAc/MeCN (3:1)23 W CFL, 20 h

OH O

Ar

Methodology

Application: selected examples

OH O

Ar

RR

16 1832 examples, 18–97%

up to >10:1 d.r.up to >99% ee

OH O

Ph Ph

OH O

Ph

OH O

Ph SPh

OH O

Ph

OH O

Ph

OH O

Ph Ph

O

Me

Cl

F3C

18a, 88%>99% ee, 2:1 d.r.

18c, 86%93% ee, 1:1 d.r.

18b, 87%93% ee, 2:1 d.r.

18d, 93%96% ee, 2:1 d.r.

18e, 42%94% ee, 2:1 d.r.

18f, 84%91% ee, 2:1 d.r.

R1R1

B(pin)

+

Ru(bpy)3(PF6)2(5 mol%)

Sc(OTf)3/L3-PiEt2Me(1:1, 10 mol%)

i-PrCN, 5 Å MS 23 W CFL, RT

OH O

Ar

Methodology

OH O

Ar

RR

16 1913 examples

56–99%up to 6.1:1 d.r.up to >92% ee

N

NHAr O

ON

O NHArAr = 2,6-Et-4-MeC6H2

L3-PiEt2Me

OH O

MeMe

Me

19a, 88%84% ee, 4.4:1 d.r.

OH O

MeMe

19b, 93%88% ee, 4.8:1 d.r.

F

OH O

Ph MeMe

19c, 85%37% ee, 5:1 d.r.

F

Selected examples

Me

MeMe

Me

O


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strategy has been harnessed by Mouriès-Mansuy, Ollivier,Fensterbank, and co-workers for the Au(I)-catalyzed forma-tion of alkynylbenzofuran derivatives 27 (Scheme 14).33

The combination of electrophilic gold catalysis and photo-sensitization by means of PS2 allowed the formation of thedecorated benzofurans 27 starting from phenols 26 andalkynyl iodide partners. The optimized reaction conditionswere applied to a series of substrates and moderate-to-ex-cellent yields of the desired alkynylbenzofurans were ob-tained. While a wide substrate scope was observed, no re-action occurred with an iodoalkyne bearing a 4-nitroarylgroup and the protodeauration cyclization product wasformed.

Detailed mechanistic investigations were carried out toshed light on the formation of 27 by performing control ex-periments, photophysical analyses and modelling studies.The reaction sequence would start by the 5-endo-dig gold-catalyzed O-cyclization of 26 to afford the vinylgold(I) spe-cies A. A Dexter-type energy transfer between this interme-diate and the long-lived triplet state 3[Ir-F] would occur toafford the excited state of the vinylgold(I) species B, a key

intermediate for triggering the oxidative addition. Gold(I)complexes are rather reluctant to oxidative addition andtherefore, specific reactions conditions are generally re-quired to provide the corresponding gold(III) intermediates.Given that triplet sensitization can promote oxidative addi-tion under convenient conditions, this strategy should offernew synthetic opportunities in the near future.

4 Conclusions and Outlook

This review has brought to light recent advances in visi-ble-light-mediated transformation of phenols by energytransfer catalysis. The unique properties of phenols enabledtheir transformation into synthetically interesting direc-tions. The hydroxyl group directly attached to the aromaticring makes phenols electron rich compounds and this prop-erty was harnessed in dearomatization reactions by meansof singlet oxygen. The hydroxyl group was also involved inO-cyclization reactions and in chelate complexes as key in-termediates to deliver [2+2] photocyclized adducts with ex-cellent selectivities. As energy transfer is not limited by theredox properties of the substrates, energy transfer catalysishas a bright future in organic synthesis and therefore inphenol chemistry. For instance, the design of new catalyticsystems is expected to tackle the challenge of asymmetricphotooxygenation of aromatic compounds such as phenolsThis review aimed at collecting examples of visible-light-driven transformations of phenols via energy transfer catal-ysis and in the near future, we hope that new examples willshow off the synthetic potential of this strategy.

Funding Information

This work was supported by The Région Pays de la Loire (NANO2 proj-ect) which financed a Ph.D. grant for J.F. We also thank University ofNantes and CNRS for financial support.Conseil Régional des Pays de la Loire (NANO2)Université de Nantes ()Centre National de la Recherche Scientifique ()

Scheme 13 Synthesis of cannabiorcicycloic acid using a [2+2] photo-cycloaddition as the key step

X

R2

Ar R1

20X = O, NTs, CH2, -(CH2)2-

X

Ar R1

R2

2123 examples

64–90%

PS2 (1 mol%)visible light

DMSO

OH

EtO2C

Me OH+

Me Me

MeOHC

OH

EtO2C

Me O

Me

Me

Me

Ca(OH)2140 °C54%

PS2 (1 mol%)visible lightDMSO, 8 h

86%

OH

EtO2C

Me OMe

HMe Me

HOH

HO2C

Me OMe

HMe Me

H LiOH60 °C

97%

Methodology

Application

cannabiorcicycloic acid

Photosensitizer

N

N

N

N

Ir+

t-Bu

t-Bu

CF3

CF3

F

F

F

F

PF6–

PS2Ir(dF(CF3)ppy)2(dtbbpy)·PF6

ET = 255 kJ/molλmax = 389 nm

22

23

24

25

Scheme 14 Merging electrophilic gold catalysis and photosensitiza-tion to prepare alkynylbenzofurans

OH

R2

R1

+

R3

I

(4-CF3C6H4)3PAuCl(5 mol%)

PS2 (1 mol%)1,10-phenanthroline

(10 mol%)

K2CO3(2.5 equiv)

MeCN, blue LEDRT, overnight

O

R1

R2

R3

2718 examples

25–83%

O

R1

R2

AuI-L

IrIII

energy transfer catalysis

cyclization

O

R1

R2

AuI-L

*

R3 IC(sp2)–C(sp)

coupling

26

A B


1624


Thi

s do

cum

ent w

as d

ownl

oade

d fo

r pe

rson

al u

se o

nly.

Una

utho

rized

dis

trib

utio

n is

str

ictly

pro

hibi

ted.

Acknowledgment

Dr. Loïc Pantaine is gratefully acknowledged for proofreading themanuscript.

References

(1) For selected references, see: (a) Visible Light Photocatalysis inOrganic Chemistry; Stephenson, C. R. J.; Yoon, T. P.; MacMillan,D. W. C., Ed.; Wiley-VCH: Weinheim, 2018. (b) Glusac, K. Nat.Chem. 2016, 8, 734. (c) Skubi, K. L.; Blum, T. R.; Yoon, T. P. Chem.Rev. 2016, 116, 10035. (d) Kärkäs, M. D.; Porco, J. A.; Stephenson,C. R. J. Chem. Rev. 2016, 116, 9683. (e) Douglas, J. J.; Sevrin, M. J.;Stephenson, C. R. J. Org. Process Res. Dev. 2016, 20, 1134.(f) Bach, T. Angew. Chem. Int. Ed. 2015, 54, 11294. (g) Bach, T.;Hehn, J. P. Angew. Chem. Int. Ed. 2011, 50, 1000. (h) Hoffmann,N. Chem. Rev. 2008, 108, 1052.

(2) (a) Marzo, L.; Pagire, S. K.; Reiser, O.; König, B. Angew. Chem. Int.Ed. 2018, 57, 10034. (b) Schultz, D. M.; Yoon, T. P. Science 2014,343, 1239176. (c) Yoon, T. P.; Ischay, M. A.; Du, J. Nat. Chem.2010, 2, 527. (d) Ravelli, D.; Dondi, D.; Fagnoni, M.; Albini, A.Chem. Soc. Rev. 2009, 38, 1999.

(3) (a) Nicholls, T. P.; Leonori, D.; Bissember, A. C. Nat. Prod. Rep.2016, 33, 1248. (b) Shaw, M. H.; Twilton, J.; MacMillan, D. W. C.J. Org. Chem. 2016, 81, 6898. (c) Tucker, J. W.; Stephenson, C. R. J.J. Org. Chem. 2012, 77, 1617. (d) Xuan, J.; Xiao, W.-J. Angew.Chem. Int. Ed. 2012, 51, 6828. (e) Narayanam, J. M. R.;Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40, 102.

(4) (a) Zhou, Q.-Q.; Zou, Y.-Q.; Lu, L.-Q.; Xiao, W.-J. Angew. Chem.Int. Ed. 2019, 58, 1586. (b) Strieth-Kalthoff, F.; James, M. J.;Teders, M.; Pitzer, L.; Glorius, F. Chem. Soc. Rev. 2018, 47, 7190.

(5) For selected recent examples, see: (a) Faßbender, S. I.; Molloy, J.J.; Mück-Lichtenfeld, C.; Gilmour, R. Angew. Chem. Int. Ed. 2019,58, 18619. (b) Oderinde, M. S.; Kempson, J.; Smith, D.;Meanwell, N. A.; Mao, E.; Pawluczyk, J.; Vetrichelvan, M.;Pitchai, M.; Karmakar, A.; Rampulla, R.; Li, J.; Dhar, T. G. M.;Mathur, A. Eur. J. Org. Chem. 2020, 41. (c) Day, J. I.; Singh, K.;Trinh, W.; Weaver, J. D. J. Am. Chem. Soc. 2018, 140, 9934.(d) James, M. J.; Schwarz, J. L.; Strieth-Kalthoff, F.; Wibbeling, B.;Glorius, F. J. Am. Chem. Soc. 2018, 140, 8624. (e) Hörmann, F. M.;Chung, T. S.; Rodriguez, E.; Jakob, M.; Bach, T. Angew. Chem. Int.Ed. 2018, 57, 827. (f) Molloy, J. J.; Metternich, J. B.; Daniliuc, C.G.; Watson, A. J. B.; Gilmour, R. Angew. Chem. Int. Ed. 2018, 57,3168. (g) Denisenko, A. V.; Druzhenko, T.; Skalenko, Y.;Samoilenko, M.; Grygorenko, O. O.; Zozulya, S.; Mykhailiuk, P. K.J. Org. Chem. 2017, 82, 9627. (h) Huang, X.; Quinn, T. R.; Harms,K.; Webster, R. D.; Zhang, L.; Wiest, O.; Meggers, E. J. Am. Chem.Soc. 2017, 139, 9120. (i) Skubi, K. L.; Kidd, J. B.; Jung, H.; Guzei, I.A.; Baik, M.-H.; Yoon, T. P. J. Am. Chem. Soc. 2017, 139, 17186.(j) Bagal, D. B.; Park, S.-W.; Song, H.-J.; Chang, S. Chem. Commun.2017, 53, 8798. (k) Welin, E. R.; Le, C.; Arias-Rotondo, D. M.;McCusker, J. K.; MacMillan, D. W. C. Science 2017, 355, 380.(l) Luis-Barrera, J.; Laina-Martín, V.; Rigotti, T.; Peccati, F.;Solans-Monfort, X.; Sodupe, M.; Mas-Ballesté, R.; Liras, M.;Alemán, J. Angew. Chem. Int. Ed. 2017, 56, 7826.

(6) Weber, M.; Weber, M.; Kleine-Boymann, M. Phenol, In Ullmann’sEncyclopedia of Industrial Chemistry, Vol. 26; Wiley-VCH: Wein-heim, 2004, 503–519.

(7) Sambiagio, C.; Marsden, S. P.; Blacker, A. J.; McGowan, P. C.Chem. Soc. Rev. 2014, 43, 3525.

(8) (a) Sun, W.; Li, G.; Hong, L.; Wang, R. Org. Biomol. Chem. 2016,14, 2164. (b) Wu, W.-T.; Zhang, L.; You, S.-L. Chem. Soc. Rev.2016, 45, 1570. (c) Pouységu, L.; Deffieux, D.; Quideau, S. Tetra-hedron 2010, 66, 2235.

(9) Huang, Z.; Lumb, J.-P. ACS Catal. 2019, 9, 521.(10) Amen-Chen, C.; Pakdel, H.; Roy, C. Bioresour. Technol. 2001, 79,

277.(11) Singlet Oxygen: Applications in Biosciences and Nanosciences;

Nonell, S.; Flors, C., Ed.; The Royal Society of Chemistry: Cam-bridge, 2016.

(12) Al-Nu’airat, J.; Dlugogorski, B. Z.; Gao, X.; Zeinali, N.; Skut, J.;Westmoreland, P. R.; Oluwoye, I.; Altarawneh, M. Phys. Chem.Chem. Phys. 2019, 21, 171.

(13) (a) Barradas, S.; Carreño, M. C.; González-López, M.; Latorre, A.;Urbano, A. Org. Lett. 2007, 9, 5019. (b) Carreño, M. C.; González-López, M.; Urbano, A. Angew. Chem. Int. Ed. 2006, 45, 2737.

(14) (a) Zilbeyaz, K.; Sahin, E.; Kilic, H. Tetrahedron: Asymmetry2007, 18, 791. (b) Adam, W.; Kilic, H.; Saha-Möller, C. R. Synlett2002, 510.

(15) Arbogast, J. W.; Darmanyan, A. P.; Foote, C. S.; Diederich, F. N.;Whetten, R. L.; Rubin, Y.; Alvarez, M. M.; Anz, S. J. J. Phys. Chem.1991, 95, 11.

(16) Hoye, T. R.; Jeffrey, C. S.; Nelson, D. P. Org. Lett. 2010, 12, 52.(17) Chen, Y.; Urano, T.; Karatsu, T.; Takahara, S.; Yamaoka, T.;

Tokumaru, K. J. Chem. Soc., Perkin Trans. 2 1998, 2233.(18) Jones, K. M.; Hillringhaus, T.; Klussmann, M. Tetrahedron Lett.

2013, 54, 3294.(19) (a) For a review, see: Ghogare, A. A.; Greer, A. Chem. Rev. 2016,

116, 9994. For other examples of photooxygenation of para-substituted phenol as a key step in total synthesis, see: (b) Park,K. H.; Chen, D. Y.-K. Chem. Commun. 2018, 54, 13018.(c) Cabrera-Afonso, M. J.; Lucena, S. R.; Juarranz, Á.; Urbano, A.;Carreño, M. C. Org. Lett. 2018, 20, 6094. (d) Kimishima, A.;Umihara, H.; Mizoguchi, A.; Yokoshima, S.; Fukuyama, T. Org.Lett. 2014, 16, 6244.

(20) Tong, G.; Liu, Z.; Li, P. Org. Lett. 2014, 16, 2288.(21) Umihara, H.; Yoshino, T.; Shimokawa, J.; Kitamura, M.;

Fukuyama, T. Angew. Chem. Int. Ed. 2016, 55, 6915.(22) Mauger, A.; Farjon, J.; Nun, P.; Coeffard, V. Chem. Eur. J. 2018, 24,

4790.(23) Wu, W.; Guo, H.; Wu, W.; Ji, S.; Zhao, J. J. Org. Chem. 2011, 76,

7056.(24) Mehta, G.; Sengupta, S. Tetrahedron 2017, 73, 6223.(25) Péault, L.; Nun, P.; Le Grognec, E.; Coeffard, V. Chem. Commun.

2019, 55, 7398.(26) Blum, T. R.; Miller, Z. D.; Bates, D. M.; Guzei, I. A.; Yoon, T. P.

Science 2016, 354, 1391.(27) Kirgan, R. A.; Witek, P. A.; Moore, C.; Rillema, D. P. Dalton Trans.

2008, 3189.(28) Ma, L.; Fang, W.-H.; Shen, L.; Chen, X. ACS Catal. 2019, 9, 3672.(29) Miller, Z. D.; Lee, B. J.; Yoon, T. P. Angew. Chem. Int. Ed. 2017, 56,

11891.(30) Yu, H.; Dong, S.; Yao, Q.; Chen, L.; Zhang, D.; Liu, X.; Feng, X.

Chem. Eur. J. 2018, 24, 19361.(31) Lu, Z.; Yoon, T. P. Angew. Chem. Int. Ed. 2012, 51, 10329.(32) Kancherla, R.; Muralirajan, K.; Sagadevan, A.; Rueping, M. Trends

Chem. 2019, 1, 510.(33) Xia, Z.; Corcé, V.; Zhao, F.; Przybylski, C.; Espagne, A.; Jullien, L.;

Le Saux, T.; Gimbert, Y.; Dossmann, H.; Mouriès-Mansuy, V.;Ollivier, C.; Fensterbank, L. Nat. Chem. 2019, 11, 797.


Documents

Visible-Light-Driven Transformations of Phenols via Energy ...€¦ · 2 Intermolecular Processes 2.1 Reactions with Singlet Oxygen 2.2 [2+2] Cycloadditions 3 Intramolecular Transformations