Buchner ring expansion

Source: Wikipedia, the free encyclopedia.
Not to be confused with Büchner–Curtius–Schlotterbeck reaction.
Buchner ring expansion
Named after Eduard Buchner
Reaction type Rearrangement reaction

The Buchner ring expansion is a two-step organic

ring expansion occurs in the second step, with an electrocyclic reaction opening the cyclopropane
ring to form the 7-membered ring.

The Buchner Ring Expansion
The Buchner Ring Expansion

History

The Buchner ring expansion reaction was first used in 1885 by

photochemical pathways in the synthesis of cycloheptatriene derivatives. The resulting product was a mixture of four isomeric carboxylic acids. Variations in the reaction arise from methods of carbene preparation. Advances in organometallic chemistry have resulted in increased selectivity of cycloheptatriene derivatives. In the 1980s it was found that dirhodium catalysts provide single cyclopropane isomers in high yields.[3] Applications are found in medicine (drug syntheses)[4][5][6][7][8] and material science (fullerene derivatives).[9][10][11]

Preparation

Preparation of ethyl-diazoacetate:

Buchner's first synthesis of cycloheptatriene derivatives in 1885 used

photolysis and thermal conditions to generate the carbene. A procedure for preparation of the hazardous starting material needed for carbene generation in the Buchner reaction, ethyl-diazoacetate, is available in Organic Syntheses.[12]
In the procedure provided, Searle includes cautionary instructions due to the highly explosive nature of diazoacetic esters.

Preparation of the metal carbenoid:

Synthesis of the carbene in the 1960s was focused on using

metallochemistry has improved the selectivity of the product ratios of the cyclohexatriene derivatives through choice of ligand on the carbenoid catalyst.[14]

Mechanism

Step 1:

The reaction mechanism of a Buchner ring expansion begins with carbene formation from ethyl-diazoacetate generated initially through photochemical or thermal reactions with extrusion of nitrogen.

carbene mechanism
carbene mechanism

The generated carbene adds to one of the double bonds of benzene to form the cyclopropane ring.

carbene insertion
carbene insertion

The advent of transition metal catalyzed reagents provides alternative stereospecific methods for cyclopropanation. The choices for metals include Cu, Rh and Ru with a variety of ligands.

π-bonds of the aromatic ring.[15]

regioselectivity
regioselectivity

The accepted carbene catalytic cycle[16] was proposed by Yates[17] in 1952. Initially the diazo compound oxidatively adds to the metal ligand complex. Following the extrusion of nitrogen the metal carbene is generated and reacts with an electron rich aromatic substance to reductively regenerate the metal catalyst completing the catalytic cycle.

catalytic cycle
catalytic cycle

Step 2:

The second step of the Buchner reaction involves a

disrotatory
(π 4s + σ 2s), thermally allowed process.

ring opening
ring opening

The norcaradiene-cycloheptatriene

conformational
effects. Due to conformational strain in the cyclopropane ring of the norcaradiene the equilibrium lies on the side of the cycloheptatriene. The equilibrium may be shifted toward the norcaradiene by destabilization of the cycloheptatriene by bulky substitution (large sterically hindered groups i. e. t-butyl) at C1 and C6.

tautomerism
tautomerism

Equilibrium may be altered by varying

electron withdrawing groups
(EWG) favor the cycloheptatriene.

equilibrium position
equilibrium position

The

antibonding
character destabilizing the norcaradiene tautomer. The position of the equilibrium may be controlled depending on the carbene substituents.

Walsh Orbitals
Walsh Orbitals

Applications

Medicine:

The importance of the Buchner ring expansion annulation chemistry is evident in the application of this synthetic sequence in the synthesis of biological compounds.

While studying an analogous reaction of carbene addition to thiophene, Stephen Matlin and Lam Chan applied the Buchner ring expansion method in 1981 to generate spiro derivatives of Penicillin.[7]

Penicillin Derivative
Penicillin Derivative

In 1998, Mander et al. synthesized the diterpenoid tropone, Harringtonolide[6] using the Buchner intramolecular ring expansion annulation chemistry. A rhodium catalyst (Rh2(mandelate)4) and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) were used to generate the carbene. This natural product was found to have antineoplastic and antiviral properties.

harringtonolide
harringtonolide

Danheiser et al. utilized

azulenes through a Buchner type ring expansion. The anti-ulcer drug, Egualen (KT1-32)[4][5]
was synthesized using this ring expansion-annulation strategy with a rhodium catalyst (Rh2(OCOt-Bu)4) in ether.

KT1-32
KT1-32

Material Science:

The Buchner ring expansion method has been used to synthesize starting materials for applications in material science involving

conducting polymer donors and buckminsterfullerene derivative acceptors create a phase-separated composite that enhances photoconductivity (available with only polymer donors) in the photoinduced charge transfer process of photovoltaic cells.[19] The fullerene compounds can be functionalized for miscibility of C60 to increase efficiency of the solar cell depending upon the polymeric thin film synthesized.[11]

fullerene derivative
fullerene derivative

Limitations

The disadvantages of the reaction involve side reactions of the carbene moiety. The choice of solvent for the reaction needs to be considered. In addition to the potential for carbon-hydrogen bond insertion reactions, carbon-halogen carbene insertion is possible when dichloromethane is used as the solvent.[20]

C-Cl bond insertion
C-Cl bond insertion

Control for regioselectivity during the carbene addition is necessary to avoid side products resulting from conjugated cycloheptatriene isomers. Noels et al. used Rh(II) catalysts for carbene generation under mild reaction conditions (room temperature) to obtain regioselectively the kinetic non-conjugated cycloheptatriene isomer.[3][8][21]

cycloheptatriene derivatives
cycloheptatriene derivatives

See also

References

  1. doi:10.1002/cber.188501802119
  2. doi:10.1002/cber.188501802118
  3. ^
    hdl:2268/237697
  4. ^
    PMID 11277800
  5. ^
    PMID 15575741
  6. ^
    doi:10.1021/ja9738081
  7. ^
    doi:10.1016/S0040-4039(01)82055-4
  8. ^
    doi:10.1055/s-0031-1289520
  9. doi:10.1039/A700080D
  10. doi:10.1021/jo00113a049
  11. ^
    doi:10.1021/jo00108a012
  12. doi:10.15227/orgsyn.036.0025
  13. ^
    PMID 12683775
  14. ^
    doi:10.1021/cr00028a010
  15. doi:10.1055/s-0030-1260562
  16. PMID 11829610
  17. doi:10.1021/ja01141a047
  18. ^
    doi:10.1016/j.tet.2010.10.030
  19. ProQuest 213566279
  20. doi:10.1016/j.tetlet.2005.02.052
  21. doi:10.1021/ja01601a080
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