Photoinduced Oxidative Alkoxycarbonylation of Alkenes with Alkyl Formates

DOI: 10.1021/acs.orglett.1c01096

Source and publish data:

Organic Letters p. 3939 - 3943 (2021)

Update date:2022-08-04

Topics: alkenes Catalyst Nucleophile Reagent Reaction Conditions Oxidative Photoinduced Photoirradiation Alkoxycarbonylation

Authors:

Tang, Wan-Ying

Chen, Ling

Zheng, Ming

Zhan, Le-Wu

Hou, Jing

Li, Bin-Dong

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Article abstract of DOI:10.1021/acs.orglett.1c01096

A photoinduced oxidative alkoxycarbonylation of alkenes initiated by intermolecular addition of alkoxycarbonyl radicals has been demonstrated. Employing alkyl formates as alkoxycarbonyl radical sources, a range of α,β-unsaturated esters were obtained with good regioselectivity and E selectivity under ambient conditions.

Full text of DOI:10.1021/acs.orglett.1c01096

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Letter

Photoinduced Oxidative Alkoxycarbonylation of Alkenes with Alkyl

Formates

Wan-Ying Tang,^†Ling Chen,^†Ming Zheng, Le-Wu Zhan, Jing Hou,* and Bin-Dong Li*

Cite This: Org. Lett. 2021, 23, 3939 −3943

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ABSTRACT: A photoinduced oxidative alkoxycarbonylation of alkenes initiated by intermolecular addition of alkoxycarbonyl

radicals has been demonstrated. Employing alkyl formates as alkoxycarbonyl radical sources, a range of α,β-unsaturated esters were

obtained with good regioselectivity and E selectivity under ambient conditions.

Tian and co-workers realized oxidative alkoxycarbonylation of

alkenes using carbazates as the carbonyl sources.⁵Nevertheless,

more readily available carbonyl sources and eﬃcient rection

patterns are still highly desirable.

α,β-Unsaturated esters are not only important synthetic

intermediates but also common scaﬀolds in numerous

biologically molecules.¹Therefore, developing eﬃcient ap-

proaches to prepare α,β-unsaturated esters has attracted much

attention in recent decades.²Among these transformations,

catalytic oxidative alkoxycarbonylation of alkenes represents a

straightforward and highly atom economical way (Scheme

1a).^2bThe ﬁrst example for selective oxidative alkoxycarbony-

lation of the styrene was reported by Cometti and Chiusoli

using PdCl₂as the catalyst and stoichiometric CuCl₂as the

oxidant.³Since then, several other Pd-catalyzed systems have

been developed.⁴However, toxic carbon monoxide (CO) has

to be used as the carbonyl source, and a high reaction

temperature is required in these reaction systems. In 2013,

Alkoxycarbonyl radicals are useful radical intermediates,

which can introduce ester groups into organic compounds

through radical addition to heterocycles or multiple bonds.⁶

However, reports of alkoxycarbonylation of alkenes initiated by

intermolecular addition of alkoxycarbonyl radicals are limited

due to the rapid decomposition of alkoxycarbonyl radicals.^6a

Taniguchi’s group realized alkene difunctionalization using

carbazates as precursors of alkoxycarbonyl radicals.⁷In 2016,

Overman’s group developed a visible-light-promoted hydro-

esteriﬁcation of electron-deﬁcient alkenes with methyl N-

phthalimidoyl oxalate as the methoxycarbonyl radical pre-

cursor.⁸Abstracting the hydrogen atom from alkyl formates

(bond dissociation energy of MeOC(O)−H, 97.2 kcal/mol),⁹

which can be prepared by catalytic hydrogenation of carbon

dioxide,¹⁰is an intriguing and eﬃcient method to generate

alkoxycarbonyl radicals. In 2019, a copper-catalyzed 1,2-

methoxy methoxycarbonylation of styrenes was disclosed by

Zhu and co-workers using methyl formate as the methox-

ycarbonyl radical precursor and di-tert-butylperoxide (TBPA)

as the oxidant.¹¹In this case, α,β-unsaturated esters could be

obtained by adding TfOH to the reaction mixtures which

contained β-methoxy alkanoate products (Scheme 1b).

However, the direct oxidative alkoxycarbonylation of alkenes

Scheme 1. Catalytic Oxidative Alkoxycarbonylation of

Alkenes

Received: March 31, 2021

Published: May 11, 2021

https://doi.org/10.1021/acs.orglett.1c01096

Org. Lett. 2021, 23, 3939−3943

3939

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Letter

Table 1. Reaction Optimization

entry

photocat.

4CzIPN

Ir(ppy)₂(dtbbpy)PF₆

Ir(ppy)₃

N-alkoxyazinium

additive (equiv)

yield (%)

E/Z

A (2.0)

B (2.0)

C (2.0)

D (2.0)

A (1.5)

A (2.0)

TMSCN (1.5)

TMSCl (1.5)

78/22

89/11

83/17

>20/1

Ru(bpy)₃Cl₂

TMSCN (1.0)

TMSCN (2.0)

TMSCN (2.0), NaHCO₃(2.0)

TMSCN (2.0), KH₂PO₄(2.0)

TMSCN (2.0)

>20/1

Ru(bpy)₃Cl₂

TMSCN (2.0)

Reaction conditions: 1a (0.2 mmol), HCOOEt (3 mL), blue LED, Ar, rt, 12 h. Isolated yield. NR = no reaction. E/Z ratio was determined by

¹H NMR. Without light.

to generate α,β-unsaturated esters triggered by the addition of

an alkoxylcarbonyl radical has not been reported.

photocatalyst, the yield of 3a was improved to 70% yield, and a

high E selectivity was observed (E/Z > 20/1). Using TMSCl

instead of TMSCN, or in the absence of the additive, the

desired ester was detected in a lower yield, and the mixture of

difunctionalization products of styrene was observed, indicat-

ing that the addition of TMSCN is essential (entries 5 and 6).

Thus, we evaluated the amount of the reagent and found that

using 2.0 equiv of TMSCN as the additive provided the best

result, giving 3a in 88% yield with excellent E selectivity

(entries 7 and 8). Employing other N-alkoxyazinium salts as

the additive delivered the desired product in a decreased yield

(entries 9−11). Reduction of the A loading to 1.5 equiv led to

a lower yield, and we reasoned that the concentration of the in

situ generated isopropoxy radical is important (entry 12). The

addition of bases, such as NaHCO₃and KH₂PO₄, resulted in

suppression of the transformation (entries 13 and 14). Without

the photocatalyst or light irradiation, the reaction could not

proceed, suggesting that both photocatalyst and light are

critical for the reaction (entries 15 and 16).

The scope of alkenes was subsequently explored with the

optimal conditions (Scheme 2). As shown in Scheme 2,

styrenes bearing electron-donating groups, such as methyl and

methoxyl groups, delivered the expected products in moderate

to good yields (3b−e). Halogen and phenyl groups were

compatible (3f−j). Notably, a boronic ester substituent on the

phenyl ring was also tolerated. 2-Vinylnaphthalene and 1,3,5-

trimethyl-2-vinylbenzene could be used to deliver product 3l in

44% yield and 3m in 39% yield. Moreover, the 1,1-diaryl-

substituted ethylenes underwent the reaction smoothly to

aﬀord the corresponding products (3n−u). α-Methylstyrene

was also a suitable substrate (3v). Gratifyingly, when we used

Recently, our group reported a visible-light-driven divergent

difunctionalization of alkenes with alkyl formates as the

alkoxylcarbonyl radical sources in a metal-free fashion.¹²In

the proposed mechanism, nucleophiles can react with carbon

cation intermediates to aﬀord alkanoate products. In this

regard, we envisioned that the carbon cation intermediates may

be converted to α,β-unsaturated esters via deprotonation in the

absence of nucleophiles. Nevertheless, in the reported system,

we found that alkanoate products could also be obtained

without external nucleophiles due to the existence of in situ

generated alcohols, including isopropanol from the isopropoxy

radical and another alcohol from the transesteriﬁcation of

isopropanol and the alkyl formate. Thus, we speculated that

α,β-unsaturated esters might be obtained successfully by

trapping the in situ generated free alochols. Herein, we

described a visible-light-driven oxidative alkoxycarbonylation

of alkenes initiated by the intermolecular addition of

alkoxycarbonyl radicals for the preparation of α,β-unsaturated

esters using alkyl formates as the carbonyl source.

On the basis of our hypothesis, we initially opted to employ

the silicon containing reagent TMSCN as the trapper of in situ

generated free alcohols. To our delight, we found that, by using

styrene (1a) and ethyl formate (2a) as substrates, 1,2,3,5-

tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN, 2 mol %)

as the photocatalyst, and A as the oxidant and oxygen radical

suppler, ethyl cinnamate (3a) was obtained successfully in 54%

yield (E/Z = 78/22) under blue LED irradiation (Table 1,

entry 1). Subsequently, other photocatalysts were investigated

(entries 2−4). Gratifyingly, when Ru(bpy)₃Cl₂was used as the

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Letter

a b

Scheme 2. Substrate Scope of Alkenes

Scheme 3. Scope of Alkyl Formates

Reaction conditions: 1 (0.2 mmol), HCOOR (1.5 mL), EA (1.5

mL), Ru(bpy)₃Cl₂(2 mol %), TMSCN (0.4 mmol), A (0.4 mmol),

blue LED, Ar, rt, 12 h. Isolated yield.

oxidative carbonylation providing the corresponding product

in moderate to good yields. Interestingly, employing the

phenyl formate as the substrate delivered α,β-unsaturated

esters successfully. However, only a low yield was obtained

using the isopropyl formate, and we reasoned that the

instability of the isopropyl carbonyl radical may suppress the

transformation. We also tested the methyl formate under the

optimized reaction conditions giving the desired product in

trace yield, and signiﬁcant amounts of difunctionalization

products were observed due to the presence of MeOH in the

purchased methyl formate.

To gain the reaction mechanism, we conducted a series of

control experiments. Based on the result of Stern−Volmer

quenching studies, the N-alkoxyazinium salt A could oxidize

the excited photocatlyst [E_1/2(P⁺/*P) = −0.81 V vs SCE in

MeCN].¹³Performing the oxidative carbonylation of styrene in

the absence of TMSCN, the major product was the β-hydroxy

ester (5a, 38% yield) and only 10% α,β-unsaturated esters (3a)

was obtained. When we added excess free isopropanol or

ethanol to the transformation, 5a was also the major product

(Scheme 4a). These results are consistent with our previous

report that the 1,2-hydroxycarbonylation product could be

genereated by a three-compontent reaction of alcohols,

formates and carbocation intermediates.¹²It has been reported

Scheme 4. Control Experiments

Reaction conditions: 1 (0.2 mmol), HCOOEt (3 mL), Ru(bpy)₃Cl₂

(2 mol %), TMSCN (0.4 mmol), A (0.4 mmol), blue LED, Ar, rt, 12

h. Isolated yield. E/Z ratio was determined by H NMR.

α-aryl cinnamates as substrates, benzylidene malonates were

obtained in good yields (3w, 3x). Finally, late-stage

functionalizations of biologically relevant complex molecules

were carried out, delivering α,β-unsaturated esters in moderate

yields (3y−aa).

The substrate scope of alkyl formates was investigated

subsequently (Scheme 3). Other alkyl formates, such as

ⁿpropyl, ⁿbutyl, and phenylethyl, were amenable to the

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Letter

that the additive TMSCN can react with alcohols to give silyl

ethers under mild conditions.¹⁴Thus, we proposed that the

role of the TMSCN reagent in this transformation was to trap

the in situ generated isopropanol and ethanol. The generation

of 3a was completely suppressed when we used TEMPO as the

additive, indicating the existence of radical intermediates

(Scheme 4b).

We propose a plausible mechanism for the photoinduced

oxidative carbonylation based on results of control experiments

(Scheme 5). The excited-state Ru(bpy)₃Cl₂can be oxidized by

AUTHOR INFORMATION

Corresponding Authors

■

Jing Hou − College of Chemical Engineering, Nanjing