Catalytic C-H Bond Activation to Organic Synthesis

A. Carbonylation through C-H Bond Activation

+

CO

h, 37oC, 16.5hRhCl(CO)(PMe3)2 (7mM)

(1 atm)

CHO + CH2OH

811%/Rh 103%/Rh

Sakakura, T; Tanaka, M. Chem. Lett. 1987, 249-252

A. CarbonylationB. HydroacylationC. DehydrogentionD. Orthoalkylation

RhCl(CO)(PMe3)2

h -CO

RhCl(PMe3)2

Ph Rh(PMe3)2

H

Cl

C Rh(PMe3)2

H

Cl

O

PhPh-CHO

PhH

CO

16e

14e

+

CO

h, r.t., 16.5hRhCl(CO)(PMe3)2

CH3 + CH3

CH3

+ CH3

2 % 63 % 35 %CHO OHC

OHC

Sakakura, T.; Tanaka, M. Chemistry Lett. 1987, 1113-1116

h, r.t., 16.5hRhCl(CO)(PMe3)2

CH3 CH2 CH2

H3C CH3CH2

H3C

+ +

221%/Rh 0% 0%

Sakakura, T.; Sodeyama, T.; Tokunaga, Y.; Tanaka, M. Chemistry Lett. 1987, 2211-2214

Cf. Orientation of Electrophilic Substitution Reaction in Aromatic Ring (Friedel-Craft Acylation Reaction, Vilsemeyer Formylation, etc.)

Meta-directing

Without CO, biaryl compounds are obtained.

RhCl(CO)(PMe3)2

hu -CO

RhCl(PMe3)2

Ar Rh(PMe3)2

H

Cl

Rh(PMe3)2

H

Cl

.

H Rh(PMe3)2

H

Cl

ArH Ar.

H.

ArH

Ar-Ar

H2

bond homolysis

Mechanism of Diarylation

h, r.t., 16.5hRhCl(CO)(PMe3)2

CH3CH2CO2CH3

CH3CH2CO2(CH2)3CO2CH3

2035 %/Rh

O

C (CH2)4CH3O C

O

OCH3

116 %/Rh

Sakakura, T.; Sodeyma, T.; Tanaka, M. Chem. Lett. 1988, 683-684

[Rh]

CO2[Rh]-H

CO2 [Rh]CO2CH3

CO2CH3

[Rh]-H

CO2CH3

[Rh]

H-[Rh]-H

CO2CH3

CO2(CH2)3CO2CH3

CO2CH3

H2

A

B

D

C

Dimerization of Esters

+CO2CH3

h, cat. Rh, r.t.CH=CH-CO2CH3

Sasaki, K.; Sakakura, T.; Tokunaga, Y.; Wada, K.; Tanaka, M. Chem. Lett. 1988, 685-688

Synthesis of methyl cinnamate from Benzene and methyl acrylate

[Rh]

H-[Rh]-PhH-[Rh]-H

CH

CO2CH3

Ph-CH2 [Rh]-H

PhH

CO2CH3

CO2CH3

CO2CH3

PhCO2CH3

PhCH2CH2-CO2CH3

B. Synthesis of Ketone from Aldehyde through C-H Bond Activation

O

CR H +R' M

RC

R'

O

Hydroacylation

O

CR H

R'

MR

CR'

OO

CR M H RC

M

O

R'M

R M H

C OR-H + M C O

Decarbonylation

A B

C

HRh(CO)L3 + [CH3CH2Rh(CO)L3]

Ph-COCl

C

Rh

O Ph

CO

LCl

L

CH3CH2

L2Rh(CO)Cl

+

Ph C

O

CH2CH3

Schwartz, J.; Cannon, J. B. J. Am. Chem. Soc. 1974, 96, 4721-4723

Hydroacylation was named by Schwartz.

O H

Rh(acac)(C2H4)2

C2H4, CHCl3

O+

O O

6 % 39 % 2 %

+

Lochow, C. F.; Miller, R. G. J. Am. Chem. Soc. 1976, 98, 1281-1283 Vora, K. P.; Lochow, C. F.; Miller R. G. J. Organomet. Chem. 1980, 192, 257-264

O H

RhCl(PPh3)3

r.t., CHCl3

O

Intramolecular Hydroacylation

CHO +R

R = H, CH3

RuCl2(PPh3)2

180-220oC, toluene R

O

R = H, CH3

Ar CHO + (1000 psi)(5-C9H7)Rh(2-C2H4)2

100oC Ar

O

Isnard, P.; Denise, B.; Sneeden, R. P. A. J. Organomet. Chem. 1982, 240, 285-288Marder, T. B.; Roe, D. C.; Milstein, D. Organometallics 1988, 7, 1451-1453

R CHO + R'-CH=CH-R"Ru3(CO)12, CO(12 KgCm-2)

200oC, 24-48hR', R" = alkyl or H

O

CR CH

R'

CH2-R"

O

CR CH

R"

CH2-R'+

R = Ar or amine

Kondo, T.; Tsuji, Y.; Watanabe, Y. Tetrahedron Lett. 1987, 28, 6229-6230Kondo, T.; Akazome, M.; Tsuji, Y.; Watanabe, Y. J. Org. Chem. 1990, 55, 1286-1291

<Principle of Le Chatelie>

N

C OH

+ RhCl(PPh3)3 N

C ORh

H

ClPh3P

Ph3P

AgBF4

1-alkene N

C OR

R = alkyl

Suggs, J. W. J. Am. Chem. Soc. 1978, 100, 640-641

CHOPh2P

+R

R = Alkyl

[(C8H14)2RhCl]2

CPh2PO R

CPh2P ORh

HL2 Cl

Lee, H.; Jun, C.-H. Bull. Korean Chem. Soc 1995, 16, 66

N

CH3

N

H Ph

+R

R = Alkyl

RhCl(PPh3)3N

CH3

N

PhR

Suggs, J. W. J. Am. Chem. Soc. 1979, 101, 489

RhClL3

N

CH3

N

PhRh

H

Cl

L2

N

CH3

N

PhRh

Cl

L2R

RhClL2

-L

R

N

CH3

N

H Ph

N

CH3

N

PhR

CHO

X

X = Br, I

+ R2 R22Pd(OAc)2, Na2CO3

Bu4NCl, DMF, 100oC

O

R1

R2

Larock, R. C.; Doty, M. J.; Cacchi, S. J. Org. Chem. 1993, 58, 4579-4583

Pd(OAc)2

Pd(0)

CHO

Pd X

CHO

Pd-X

R2 R1

Pd-X

R2R1

OH

O

R1

R2

CHO

X

R2 R2Base-HX

Pd

R2R1

O

Annulation Reaction

(CH2)6CO2MeMeO

(CH2)7MeHOCH2

Hg(OAc)2

120oC, 10h

O

(CH2)6CO2Me

(CH2)7Me

OHC (CH2)6CO2Me

(CH2)7Me

(PPh3)3RhCl

(CH2)7Me

O(CH2)6CO2Me

(CH2)6CO2Me

(CH2)7Me

O

RhH (CH2)6CO2Me

(CH2)7Me

RhHCO

(CH2)6CO2Me

(CH2)7Me

30% 30%

Sakai, K.; Ide, J.; Oda, O.; Nakamura, N. Tetrahedron Lett. 1972, 13, 1287-1290

Synthesis of Cyclopentanone Derivatives

CHO + Rh(PMe3)3Cl RhPMe3Cl

Me3P H

PMe3

O

Milstein, D. J. Chem. Soc., Chem. Comm. 1982, 1357-1358

D

O

(PPh3)3RhCl

O

CH3

DCH3H

H

O

RhD Rh

O

CH3D

HH

Campbell, Jr. R. E.; Lochow, C. F.; Vora, K. P.; Miller, R. G. J. Am. Chem. Soc. 1980, 102, 5824-5830

Isolation of intermediate, cis-hydrido pent-4-enoyl rhodium(III) complexes

Stereochemistry of intramolecular hydroacylation

P P

a

e

e

a

S-binap

P P

a

e

e

aRh

t-Bu

H P P

a

e

e

aRh

H

t-BuOO

Barnhart, R. W.; Wang, X.; Noheda, P.; Bergens, S. H.; Whelan, J.; Bosnich, B. J. Am. Chem. Soc. 1994, 116, 1821-1830

C. Decarbonylation through C-H Bond Activation

+RCH2CH2CHO

RCH2CH3 + M-CO

RCH2=CH2 + H2 + M-CO

A

B

MRCH2CH2 C

O

MRCH2CH2 M CO

RCH2CH2 M CO

HH

H

+ArCHO MAr C

O

M

H

Ar M CO

HAr-H + M-CO

Decarbonylation of Aromatic aldehyde

Decarbonylation of Aliphatic aldehyde

Common method for decarbonylation of aldehyde: oxidation of aldehydeand pyrolysis of decarboxylation of the resulting carboxylic acid. Some carboxylic acid is too stable to be decarboyxylated.

Pd/C (5%)

190oC, 2h

57%

27%+

PhCHO

Pd/C (5%)

185oC, 2hPh

37%

CH3(CH2)8 CHO

CH3-(CH2)7-CH3

HC CH2CH3(CH2)7

Tsuji, J.; Ohno, K. A. J. Am. Chem. Soc. 1968, 90, 94

+ (PPh3)3RhClr.t., 24h

+ RhCl(CO)(PPh 3)2 + PPh3

CHO H

Rh(CO)Cl(PPh 3)2 (cat.)+

CHO H

Cl Cl

220oC, 9hCO

Ohno, K.; Tsuji, J. J. Am. Chem. Soc. 1968, 90, 99

only product

stoichiometric reaction

catalytic reaction

RhCl(CO)(PPh 3)2

O2

h[RhClO2(O=PPh3)0.67]x

CO2 + 1.33 Ph3P=O

PPh3

N2

RhCl(PPh3)3

Geoffroy, G. L.; Denton, D. A.; Keeney, M. E.; Bucks, R. R. Inorg. Chem. 1976, 15, 2382

Regeneration of Wilkinson’c complex

OHC

O

MeOH

Me

H

(PPh3)3RhClO

MeOH

Me

H

+CH2Cl2, relux

80%

+ Rh(CO)Cl(PPh3)2

HO

H

CHO

(PPh3)3RhCl+

HO

H

+ Rh(CO)Cl(PPh3)2

CHO

CHO

(PPh3)3RhCl+ + Rh(CO)Cl(PPh3)2PhH, reflux

88%

Use in natural product synthesis

Occidentanol

Lanosterol derivatives

annulene

CDO

Me

Ph

Ph xylene, reflux, 16h

D

Me

Ph

Ph(PPh3)3RhCl

Me

MeO2C CH2CHO

Me

MeO2C CH3

+

94%

+ Rh(CO)Cl(PPh3)2

+ Rh(CO)Cl(PPh3)2(PPh3)3RhCl+CH3CN, relux

64%

Walborsky, H. M.; Allen, L. E. J. Am. Chem. Soc. 1971, 93, 5465. Trost, B. M.; Preckel, M. J. Am. Chem. Soc. 1973, 95, 7862.

Andrews, M. A.; Klaeren, S. A.; J. Chem. Soc., Chem. Comm. 1988, 1266. Andrews, M. A.; Gould, G. L.; Klaeren, S. A. J. Org. Chem. 1989, 54, 5257

Retension of stereochemistry of carbon next to aldehyde

130oC, 5h

Glucose

O

CH2OH

HH

OH

OH

HH

OH

OH

H

(PPh3)3RhCl

+CHO

H OH

HO H

H OH

H OH

CH2OH

NMP

H

H OH

HO H

H OH

H OH

CH2OHArabinitol

88%

(PPh3)3RhCl

Rh(13CO)Cl(PPh3)2

Rh(CO)Cl(PPh3)2

NMP =N

Me

O

13CH2OH

O

HO H

H OH

H OH

CH2OH

130oC, 2h

NMP

(PPh3)3RhCl

+13CHO

O

HO H

H OH

H OH

CH2OH

2(PPh3)3RhCl

CH3

H OH

H OH

CH2OH

+

+ Rh(CO)Cl(PPh3)2

-2H2O

O CH2OHOHC (PPh3)3RhCl O CH2OH

ºÎ ¹ÝÀÀ

ÁÖ¹ÝÀÀ

79%

furfuryl alcohol

1-deoxyerythritol

5%

-H2

Fructose

0.002% without NMP

Ph CHO

or

CH3(CH2)5-CHO

[Rh(dppe)2]+l

or [Rh(dppp)2]+

115-180oC

Ph H

or

CH3(CH2)4CH3

dppe = Ph2PCH2CH2PPh2 dppp = Ph2PCH2CH2CH2PPh2

Doughty, D. H.; Pignolet, L. H.  J. Am. Chem. Soc. 1978, 100, 7083

Since the bond of common Rh and CO bond is very strong, it is hard toLiberate CO. But CO binded to Rh+ species are easily to be dissociatedDue to weak -back donation.

[Rh(dppp)2]+Cl-

NH

CH3OBr

CO2Eta) LiAlH4

b) MnO2 NH

CH3OBr

CHO

xylene, relux, 18hNH

CH3OBr

77% 95%

(4 mol%)

Meyer, M. D.; Kruse, L. I. J. Org. Chem. 1984, 49, 3195

CH2CHO

H3C CH3

CH3

CH3

H3C CH3

CH3

99%

(PPh3)3RhCl+

DPPA

O

PN3PhO

PhO

THF, r.t. , 45h

O

PNCOPhO

PhO+

O'connor, J. M.; Ma, J. J. Org. Chem. 1992, 57, 5075

Elimination of carboxylic ester

Elimination of aldehyde under very mild conditions

isocyanate

RhPPh3Cl

Ph3P CORh

PPh3Cl

Ph3P L

R H

OR-H

O

PN3PhO

PhO

O

PNCOPhO

PhO

RhPPh3Cl

Ph3P CO

O

PN3PhO

PhO

RhPPh3Cl

Ph3P N

CO

N N

PO

OPh

OPhRh

PPh3Cl

Ph3P N2

O

PNCOPhO

PhO

+

H C

O

O-CH2CH2PhRu3(CO)12, (CH3)3NO.2H2O

200oc, 6h, ArHO-CH2CH2Ph

100%

[Ru] C

O

O-CH2CH2PhH [Ru] O-CH2CH2PhH

CO

Kondo, T.; Tantayanon, S.; Tsuji, Y.; Watanabe, Y.  Tetrahedron Lett. 1989, 30, 4137

(CH3)3NO is a promoter to make unsaturation of Ru3(CO)12.

CHO [Rh(CO)(triphos)][SbF6] (5 mol%)

diglyme, reflux, 48h

triphos =Ph2P

PPPh2

Ph

100%

Beck, C. M.; Rathmill, S. E.; Park, Y. J.; Chen, J.; Crabtree, R. H. Organometalics 1999, 18, 5311

Retard the formation of byproducts