Rhenium-Catalyzed Synthesis of

Multisubstituted Aromatic Compounds via

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

R6
O O R5 R2
cat. [ReBr(CO)3(thf)]2
R1 OEt + R3 R4 + R5 R6
R2 R1 R4
R3

Current Literature
Kalyani Patil
6/28/08

Kalyani Patil @ Wipf Group Page 1 of 13 7/3/2008

 Outline

• Synthesis of Substituted Aromatic Compounds

• Rhenium Catalyzed Reactions

• Rhenium Catalyzed C-H Activation - Takai Group

• Title Paper

• Summary

Kalyani Patil @ Wipf Group Page 2 of 13 7/3/2008

 Synthesis of Substituted Aromatic Compounds
Bergman cyclization
H
R3 R3 H
R1 150-200 °C R1 R1 R3 R1 R3 R1 R3
benzene
Bergman et. al. J. Am.
R2 cyclohexadiene R2 R2 R4 R2 R4 R2 R4 Chem. Soc. 1972, 94, 660
R4 R4 H H
H

Trimerization of acetylenes
R1
R1
+
CpCo(CO)2
CH2
Vollhardt Angew. Chem. Int. Ed.
(CH2)n
30 - 95% R2 1984, 23, 539
R2

+ + MLx-2
MLx MLx-1 MLx-2
1 2 3

+ +
• Oxidative coupling to give metallacyclopentadiene
MLx-2 MLx-2
• Alkyne insertion or Diels-Alder type addition
5 4

MLx-2

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 Synthesis of Substituted Aromatic Compounds
Ring-closing metathesis
O O
n-Pr OH
Grubbs' II n-Pr
n-Pr
CH2Cl2, rt, 2h
n-Pr
Imamoto et. al. J. Am. Chem. Soc.
n-Pr
n-Pr 2005, 127, 10470

Annulation of vinylketenes with acetylenes

O OH
+ benzene, 80 °C, 26h
OCH3
H3CO

4 e- electrocyclic 6 e- electrocyclic Danheiser et. al. J.Org. Chem.

cleavage closure
1984, 49, 1672
O O
O 4 e- electrocyclic
[2+2] cleavage
H3CO H3CO

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 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

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 Rhenium Catalyzed Reactions
Friedel-Crafts alkylation

+ t-BuCl ReBr(CO)5 (1 mol%) Sonoda et. al. Bull. Chem. Soc. Jpn.
ClCH2CH2Cl, 84 °C
93%
t-Bu 2000, 73, 2779
OCH3 OCH3

Anti-Markovnikov addition of carboxylic acids to terminal alkynes

O
ReBr(CO)5 (1 mol%)
O
O Ph
Hua et. al. J. Org. Chem.
+ PhCOOH Ph +
Ph
toluene, 110 °C O Ph Ph 2004, 69, 5782
67% 13:87

Coupling of epoxides with CO2

O ReBr(CO)5 (0.1 mol%) Ph O

Hua et. al. J. Org. Chem.
+ CO2
Ph 110 °C, 85%
O 2005, 70, 381
O

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 Rhenium Catalyzed Reactions - Toste Group
Etherification of propargylic alcohols

1 mol% (dppm)ReOCl3
OH O Cl
Toste et. al. J. Am. Chem. Soc.
Ph Cl OH Ph
H H 2003, 125, 6076
n-Bu MeCN, 65 °C n-Bu
78%
[M]
OH [M] O O O O
X O [3,3] R1 H+
[M]
R1 R1 O R1 R2
-HX
R2 R2 1 R2 2
[O] R3OH

O OR3

R1 R1
3 R2 R2

Synthesis of 1,5-Enynes

5 mol% (dppm)ReOCl3
OH
Ph TMS cat. NH4PF6
Ph
Toste et. al. J. Am. Chem. Soc.
+
H
MeNO2, 65 °C
H 2003, 125, 15760
Ph 79% Ph

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 Rhenium Catalyzed Ring Expansion - Takai Group
O
O O [ReBr(CO)3(thf)]2 (2.5 mol%)
PhCH2NC (5 mol%) Ph
R + Ph
Construction of medium size rings n
neat, 24h O
n
R
O
Insertion of terminal alkynes into C-C O Ph
O
Ph O O
O
next to the carbonyl group Ph Ph
OEt OEt O O

OEt
87% 78% 78% 61%

O O O OH O
R
OEt OEt
O
(4-b)
HO OEt

R Re (I)
R
O (4-a)

OEt
(3-b)
• Rhenacyclopentene intermediate
HO Re
R HO
O (2-b)
R • Retro-aldol reaction/isomerization
O
OEt OEt
(2-a)
• Reductive elimination
O HO
Re Re
R (3-a) R
O O

OEt OEt

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

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 Rhenium Catalyzed C-H Activation - Takai Group
Formation of indene derivatives

t-Bu HN t-Bu
N
+ Ph Me
cat. [ReBr(CO)3(thf)]2
Ph
Takai et. al. J. Am. Chem. Soc.
H
toluene, reflux, 24h
95%
2005, 127, 13498

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

+ CO2Et
p-anisidine (15 mol%)
CO2Et Takai et. al. Angew. Chem. Int. Ed.
toluene, 180 °C, 24h
93% 2006, 45, 2766

Synthesis of isobenzofuran

Ph O cat. [ReBr(CO)3(thf)]2 Ph
N
Ph
+ Ph
MS 4Å Takai et. al.J. Am. Chem. Soc.
H toluene, reflux, 24h
93%
O
2006, 128, 12376
Ph

Kalyani Patil @ Wipf Group Page 9 of 13 7/3/2008

 Title Paper
O R6
O O [ReBr(CO)3(thf)]2 (2.5 mol%)
R2 R5 R2
MS 4Å (200 wt%-Re cat.) O R5 R6
R1 OEt + R3 R4
toluene, 180 °C, 24h toluene, 150 °C, 24h
R2 R1 R4 R1 R4
R3 R3

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 H Ph Ph CO2Et CO2Et 84
4. Me Me Me Ph CO2Et CO2Et 91
5. Me Me H Ph CO2Et CO2Et 87

6. Me Me H n-C10H21 CO2Et CO2Et 72

7. Me n-C5H11 n-C6H13 Ph CO2Et CO2Et 85, A:B = 96:4

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

9. Me Me Ph Ph CO2Et H 83

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

CO2Et CO2Et CO2Et

EtO2C n-C5H11 EtO2C EtO2C

Ph n-C5H11 Ph Ph Ph Ph Ph
n-C6H13 n-C6H13 Ph Ph
A B C D

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

Kalyani Patil @ Wipf Group Page 10 of 13 7/3/2008

 Title Paper
DA w/ Benzyne
O
O O [ReBr(CO)3(thf)]2 (2.5 mol%)
R OEt +
Ph Ph MS 4Å (200 wt%-Re cat) O Benzyne generated in situ to
1 eq. toluene, 180 °C R Ph synthesize naphthalene derivatives
1 (1eq.) Ph

SiMe3
, CsF(3 eq.) Ph R time (h) yield (%)
OTf Me (1a) 24 92 (2a)
(1.5 eq.) Ph Ph (1b) 48 96 (2b)
toluene/CH3CN, 20 °C, 12h R
2

Intramolecular Reaction
O
O O
[ReBr(CO)3(thf)]2 (2.5 mol%) O
OEt Ph MS 4Å (100 wt%-Re cat)
toluene, 150 °C, 24h
Ph
Synthesis of tetrahydronaphthalene
derivatives
CO2Me
MeO2C CO2Me MeO2C
(4 eq.) (84%)
toluene, 150 °C, 48h
Ph

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

Kalyani Patil @ Wipf Group Page 11 of 13 7/3/2008

 Title Paper: Proposed Mechanism

O O OH O

R1 OEt R1 OEt
O R6 R2 R2
O R2 (6) R5 R2

R5
R6 R4
R3 -CO2 (1)
R3 • Rhenacyclopentene intermediate
R1 R4 Re (I)
R1 R4
R3
(5) R5 R6 • Retro-aldol reaction/reductive
O elimination
R2 R1 R2 R1 R2
O O CO2Et O CO2Et
H (2-b) H
Re R4
• Isomerization of the alkene/cyclization
R1 R4
R3 R4
R3 R3
(3-b) • DA reaction/decarboxylation
(4) (2-a)
-EtOH
O
EtO R2 R2 CO2Et
O H (3-a) R1 Re
R4
R1 R4
O R3
R3

Kuninobu, Y.; Takata, H.; Kawata, A.; Takai, K. Org. Lett. ASAP
Kalyani Patil @ Wipf Group Page 12 of 13 7/3/2008
 Summary

• Synthesis of Multisubstituted Aromatic Compounds in Good

Yields

• Products are Obtained in High Regioselectivity

• Aliphatic and Aromatic Acetylenes employed Prior to DA

Reaction

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