rhenium-catalyzed synthesis of multisubstituted aromatic ...ccc.chem.pitt.edu/wipf/current...

Rhenium-Catalyzed Synthesis ofMultisubstituted Aromatic Compounds via

C-C Single-Bond Cleavage Kuninobu, Y.; Takata, H.; Kawata, A.; Takai, K. Org.

Lett. ASAP

Current LiteratureKalyani Patil

6/28/08

R6

R2

R4

R3

R1

R5

R1 OEt

O O

R2

+ R3 R4 + R5 R6cat. [ReBr(CO)3(thf)]2

Kalyani Patil @ Wipf Group of 13 7/3/2008

Outline

• Synthesis of Substituted Aromatic Compounds

• Rhenium Catalyzed Reactions

• Rhenium Catalyzed C-H Activation - Takai Group

• Title Paper

• Summary


Synthesis of Substituted Aromatic CompoundsBergman cyclization

Vollhardt Angew. Chem. Int. Ed.1984, 23, 539

Trimerization of acetylenes

Bergman et. al. J. Am. Chem. Soc. 1972, 94, 660

R3

R4

R1

R2

150-200 °C

benzenecyclohexadiene

R3

R4

R1

R2

R1

R2

R3

R4

H

R1

R2

R3

R4

H

H

R1

R2

R3

R4

H

H

(CH2)n +

R1

R2

CpCo(CO)2

30 - 95%

R1

R2

CH2

MLxMLx-1

+ +MLx-2

MLx-2

+

MLx-2

1 2 3

4

MLx-2

5

+

6

MLx-2

• Oxidative coupling to give metallacyclopentadiene

• Alkyne insertion or Diels-Alder type addition


Synthesis of Substituted Aromatic CompoundsRing-closing metathesis

OH

n-Pr

n-Pr

On-Pr

n-Pr

Grubbs' II

CH2Cl2, rt, 2h

O

n-Pr

n-Pr

Danheiser et. al. J.Org. Chem.1984, 49, 1672

OCH3

+O

4 e- electrocyclic

cleavage

O

[2+2]

O

H3CO

4 e- electrocyclic

cleavage

O

H3CO

6 e- electrocyclic

closure

OH

H3CO

benzene, 80 °C, 26h

Annulation of vinylketenes with acetylenes

Imamoto et. al. J. Am. Chem. Soc.2005, 127, 10470


Properties of Rhenium

• Grayish white metal, last naturally occurring element to be discovered

• Discovered in 1925 by Dr. Walter Noddack and Dr. Ida Tacke Noddack

• Electronic configuration: [Xe] 4f14 5d5 6s2

• Oxidation states: -3, -1, 0, +1 to +7

• Lower electronegativity than Ru and Rh


Rhenium Catalyzed Reactions

Friedel-Crafts alkylation

+ t-BuClReBr(CO)5 (1 mol%)

ClCH2CH2Cl, 84 °C

OCH3 OCH3

t-Bu93%

Sonoda et. al. Bull. Chem. Soc. Jpn.2000, 73, 2779

Anti-Markovnikov addition of carboxylic acids to terminal alkynes

Ph + PhCOOHReBr(CO)5 (1 mol%)

toluene, 110 °CPh

O Ph

O

+ O Ph

O

Ph

67% 13:87

Hua et. al. J. Org. Chem.2004, 69, 5782

Coupling of epoxides with CO2

O

Ph

+ CO2ReBr(CO)5 (0.1 mol%)

110 °C, 85%O

O

O

Ph Hua et. al. J. Org. Chem.2005, 70, 381


Rhenium Catalyzed Reactions - Toste GroupEtherification of propargylic alcohols

Toste et. al. J. Am. Chem. Soc.2003, 125, 6076

n-Bu

OH

H

Ph

1 mol% (dppm)ReOCl3

Cl OH

MeCN, 65 °C n-Bu

O

H

Ph

Cl

78%

R2

OH

R1

X[M]

O

-HXR2

O

R1

[M]O

[3,3] R1

R2

O[M]

OH+

R1 R2

O

1 2

[O]

R2

O

R13 R2

OR3

R1

R3OH

Synthesis of 1,5-Enynes

Ph

OH

H

Ph

5 mol% (dppm)ReOCl3

MeNO2, 65 °C

PhH

Ph

79%

TMS+

cat. NH4PF6 Toste et. al. J. Am. Chem. Soc.2003, 125, 15760


Rhenium Catalyzed Ring Expansion - Takai Group

Takai et. al. J. Am. Chem. Soc.2006, 128, 12376

O O

R

n

+ Ph

[ReBr(CO)3(thf)]2 (2.5 mol%)

neat, 24h

PhCH2NC (5 mol%)

O

Ph

R

O

n

O PhO

OEt

O

Ph

O

OEt

O

Ph

OEt

O

O

Ph

O

87% 78% 78% 61%

O O

OEt

ReHO

OH O

OEt

O

R

OEt

O

HO

R

OEt

O

(4-b)

RHO

OEt

O

(3-b)

R

ReHO

R

OEt

O

(2-a)

R

OEt

O

Re (I)

(3-a)

ReO

R

OEt

O

(2-b)

(4-a)

Construction of medium size rings

Insertion of terminal alkynes into C-Cnext to the carbonyl group

• Rhenacyclopentene intermediate

• Retro-aldol reaction/isomerization

• Reductive elimination


Rhenium Catalyzed C-H Activation - Takai GroupFormation of indene derivatives

Takai et. al. Angew. Chem. Int. Ed.2006, 45, 2766

Takai et. al. J. Am. Chem. Soc.2005, 127, 13498

Synthesis of isobenzofuran

Takai et. al.J. Am. Chem. Soc.2006, 128, 12376

N

H

t-Bu

+ Ph Mecat. [ReBr(CO)3(thf)]2

toluene, reflux, 24h

HN

Ph

t-Bu

95%

O

+

cat. [ReBr(CO)3(thf)]2

toluene, 180 °C, 24hCO2Et

93%

CO2Et

p-anisidine (15 mol%)

Ph

N +

cat. [ReBr(CO)3(thf)]2

toluene, reflux, 24h O

Ph

Ph

93%

Ph

Ph

O

H

MS 4Å


Kuninobu, Y.; Takata, H.; Kawata, A.; Takai, K. Org. Lett. ASAP

Title Paper

R6

R2

R4

R3

R1

R5

R1 OEt

O O

R2

+ R3 R4

R5 R6

[ReBr(CO)3(thf)]2 (2.5 mol%)MS 4Å (200 wt%-Re cat.)

toluene, 180 °C, 24h

O

O

R2

R4

R3

R1toluene, 150 °C, 24h

Entry R1 R2 R3 R4 R5 R6 Yield (%)

1. Me Me Ph Ph CO2Et CO2Et 83

2. Ph Me Ph Ph CO2Et CO2Et 64

3. Me Ph Ph CO2Et CO2Et 84

4. Me Me Me Ph CO2Et CO2Et 91

H

5. Me Me Ph CO2Et CO2Et 87

6. Me Me n-C10H21 CO2Et CO2Et 72

7. Me n-C6H13 Ph CO2Et CO2Et 85, A:B = 96:4

8. n-C5H11 Me n-C6H13 Ph CO2Et CO2Et 83, A:B = 6:94

n-C5H11

H

H

9. Me Me Ph Ph CO2Et 83

10. Ph Me Ph Ph CO2Et 77, C:D = 39:61

H

H

CO2Et

n-C5H11

Ph

n-C6H13

EtO2C

CO2Et

Ph

n-C6H13

n-C5H11

EtO2C

CO2Et

Ph

Ph

Ph Ph

Ph

Ph

EtO2C

A B C D


DA w/ Benzyne


R OEt

O O [ReBr(CO)3(thf)]2 (2.5 mol%)MS 4Å (200 wt%-Re cat)

+Ph Ph

toluene, 180 °C

O

O

Ph

R Ph

SiMe3

OTf

1 (1eq.)

1 eq.

(1.5 eq.)

, CsF(3 eq.)

toluene/CH3CN, 20 °C, 12h

Ph

Ph

R

2

R time (h) yield (%)

Me (1a) 24 92 (2a)

Ph (1b) 48 96 (2b)

Title Paper

Intramolecular Reaction

OEt

O O

Ph

[ReBr(CO)3(thf)]2 (2.5 mol%)MS 4Å (100 wt%-Re cat)


O

O

Ph

MeO2C CO2Me

(4 eq.)


CO2Me

Ph

MeO2C

(84%)

Benzyne generated in situ tosynthesize naphthalene derivatives

Synthesis of tetrahydronaphthalene derivatives


Title Paper: Proposed Mechanism


R1

R2

O O

OEt R1

R2

OH O

OEt

(3-b)

R4

(2-a)

Re (I)

(3-a)

(2-b)

R3(1)

Re

R3

R4

R2R1O CO2Et

H

Re

R2

R1

O R3

CO2Et

R4

O

R1

R3

R4

OR2

H

EtO

R4R3

O CO2Et

R1 R2

H

O

O

R1

R3

R4

R2

(4)-EtOH

O

O

R4R3

R1

R2

R5

R6

(5) R5 R6

R6

R2

R4

R3

R1

R5(6)

-CO2• Rhenacyclopentene intermediate

• Retro-aldol reaction/reductive elimination

• Isomerization of the alkene/cyclization

• DA reaction/decarboxylation


Summary

• Synthesis of Multisubstituted Aromatic Compounds in Good Yields

• Products are Obtained in High Regioselectivity

• Aliphatic and Aromatic Acetylenes employed Prior to DA Reaction


rhenium-catalyzed synthesis of multisubstituted aromatic ...ccc.chem.pitt.edu/wipf/current...

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