Ni-Catalyzed Carboxylation of

C(sp2)- and C(sp3)-O Bonds with CO2

A. Correa, T. Leon, R. Martin, J. Am. Chem. Soc., 2014, 136, 1062

04/04/14

Rachel Nicholls

● Aim: synthesis of aryl and benzyl carboxylic acids:

● Carboxylic acids:

– Important intermediates in organic synthesis

– Common motifs in natural products, agrochemicals or

pharmaceuticals

Introduction

● Use of CO2 for COOH synthesis:

– Low cost

– High abundance

– Renewable carbon source

– High kinetic and thermodynamic stability

● Requires use of high energy reactants

– E.g. Organolithiums and Grignard reagents

Introduction

W. Leitner, Coord. Chem. Rev., 1996, 153, 257

● Advancements on organometallic processes:

– Less activated M-C bonds:

Aryl Carboxylic Acid Synthesis

K. Ukai, M. Aoki, J. Takaya and N. Iwasawa, J. Am. Chem. Soc., 2006, 128, 8706-8707

● Advancements on organometallic processes:

– Less activated M-C bonds:

– Aryl Halides:

Aryl Carboxylic Acid Synthesis

K. Ukai, M. Aoki, J. Takaya and N. Iwasawa, J. Am. Chem. Soc., 2006, 128, 8706-8707 A. Correa, R. Martin, J. Am. Chem. Soc., 2009, 131, 15974

Benzyl Carboxylic Acid Synthesis

● From styrenes:

● From organohalides:

Limitations:

– Pyrophoric and air sensitive reagents

– Limited substrate scope

– Restricted to organic halide derivatives

M. D. Greenhalgh and S. P. Thomas, J. Am. Chem. Soc., 2012, 134, 11900-11903 T. Leon, A. Correa, R. Martin, J. Am. Chem. Soc., 2013, 135, 1221-1224

● Aim: Develop carboxylation procedure utilising

readily available phenol derivatives as

substrates

– Mild and operationally simple

– Wide substrate scope

– Readily available coupling partners

Aryl and Benzyl Carboxylations

● Few examples of simple aryl and benzyl esters in C-O

bond cleavage, although no reported carboxylation

reactions

● Limitations:

i) High activation energy of C(sp2)-O bond

ii) Under basic conditions ester may commonly be cleaved

iii) Two possible reaction sites

● Limited to extended π systems

C-O Bond Cleavage

● Initial Target:

– 2-Naphthyl pivalate substrate

Ni-Catalysed Reductive Carboxylation of

C(sp2)-O Bonds

Ni-Catalysed Reductive Carboxylation of

C(sp2)-O Bonds

● Substrate scope:

– Stabilisation effect of bulkier substituents

Ni-Catalysed Reductive Carboxylation of

C(sp2)-O Bonds

● Chemoselectivity:

– Range of naphthyl derivates with EWG and EDG tested

– High chemoselectivity with amines, amides, esters, nitro and N containing

heterocycles

– Resistant to C-O bond cleavage

– Site selective to naphthyl pivalates:

Ni-Catalysed Reductive Carboxylation of

C(sp2)-O Bonds

Ni-Catalysed Reductive Carboxylation of

Benzylic C(sp3)-O Bonds

● Substrate scope:

– Sterically demanding leaving groups are less important, e.g.

acetate, carbamate and other esters

● Chemoselectivity:

– Selective for benzylic C(sp3)-O bonds over C(sp2)-O bonds

– Reaction slower for C1 position

– Successful for heterocyclic motifs (limited when benzyl halides

used for substrates)

Ni-Catalysed Reductive Carboxylation of

Benzylic C(sp3)-O Bonds

● C-O bond cleavages generally limited to π-extended systems

Use of Traceless Directing Groups

● C-O bond cleavages generally limited to π-extended systems

Use of Traceless Directing Groups

● Proposed a hemilabile directing group in the ester may increase

oxidative addition rate with regular arenes

Use of Traceless Directing Groups

● Proposed a hemilabile directing group in the ester may increase

oxidative addition rate with regular arenes

● Use of pyridine and ester coordinating groups resulted in reaction

Use of Traceless Directing Groups

Proposed Mechanism

Mechanism based on: J. Tsuji et al. , J. Am. Chem. Soc., 2012, 134, 9106

1) Mn assisted reduction of Ni(II)

2) Oxidative addition

3) Mn assisted reduction of Ni(II)

4) CO2 insertion

5) Transmetallation

Hydrolytic workup

● Developed a Nickel catalysed reductive carboxylation

methodology to couple aryl or benzyl esters with CO2 – Cheap phenol derivatives as starting materials (alternative to aryl

halides)

– Avoids use of air and moisture sensitive reagents

– Chemoselective

– Wide reaction scope

– Access heterocyclic motifs previously inaccessible via

benzylhalides

● Use of a traceless directing group removes requirement

for extended pi system

Conclusions