Anti-Bredt alkenes, bicyclic molecules that contain a bridgehead double bond, were for many years regarded as chemical curiosities The type 2 intramolecular Diels-Alder (IMDA) reaction provides a one-step entry into this fascinating class of molecules The reaction has made available numerous anti-Bredt alkenes for structural and chemical studies X-ray crystallography has revealed the magnitude of the deformations associated with the bridgehead double bond, and rate studies of reactions of bridgehead alkenes have allowed quantification of the kinetic consequences of the torsional distortions More recently, the type 2 intramolecular Diels-Alder reaction and the resulting anti-Bredt alkenes have found application in organic synthesis The constraints resulting from the connectivity in the Diels-Alder precursor creates a strong regio- and stereochemical bias in the cycloaddition step The end result of this bias is the stereoselective synthesis of highly substituted six-membered rings The reaction also achieves a facile synthesis of seven- and eight-membered rings in a single step from acyclic precursors The utility of this reaction has been verified in recent applications of the type 2 IMDA reaction as a key step in the total synthesis of complex natural products

The Type 2 Intramolecular Diels–Alder Reaction: Synthesis and Chemistry of Bridgehead Alkenes

The type two intramolecular Diels−Alder reaction (T2IMDA) is an efficient method for the formation of medium rings. The methodology is particularly effective for the construction of seven- and eight-membered rings. A strategy for the synthesis of functionalized cycloheptanes and cyclooctanes has been developed that involves a bridged to fused ring interchange. The T2IMDA provides a synthesis for rigid bridged bicyclic molecules that can be stereoselectively elaborated before ozonolysis of the bridgehead double bond. Following oxidative cleavage, aldol condensation provides fused bicyclic ring systems that otherwise are difficult to synthesize. This methodology is amenable to the synthesis of terpene natural products. This is demonstrated here through total syntheses of (±)-ledol and (±)-ledene and a formal synthesis of (±)-compressanolide.

Bridged to Fused Ring Interchange. Methodology for the Construction of Fused Cycloheptanes and Cyclooctanes. Total Syntheses of Ledol, Ledene, and Compressanolide.

Anti-Bredt-Alkene, bicyclische Molekule mit einer Bruckenkopf-Doppelbindung, galten lange als chemische Kuriositat. Mit der intramolekularen Diels-Alder-Reaktion vom Typ 2 gelangt man in einem Reaktionsschritt zu dieser faszinierenden Klasse von Molekulen, und man erhielt so zahlreiche anti-Bredt-Alkene fur Strukturuntersuchungen und chemische Studien. Kristallstrukturanalysen zeigten das Ausmas der mit der Bruckenkopf-Doppelbindung einhergehenden Deformationen auf, und die Messung von Reaktionsgeschwindigkeiten ermoglichte quantitative Aussagen zu kinetischen Konsequenzen der Verzerrungen. In neuerer Zeit wurden die intramolekulare Diels-Alder-Reaktion vom Typ 2 und die dabei entstehenden anti-Bredt-Alkene auch in der praparativen Organischen Chemie eingesetzt. Die aus der Art der Verknupfungen in der Vorstufe resultierenden Einschrankungen bewirken im Cycloadditionsschritt eine starke regio- und stereochemische Praferenz mit dem Ergebnis einer stereoselektiven Synthese hochsubstituierter Sechsringe. Die Reaktion ermoglicht aber auch in einem Schritt eine einfache Synthese von Sieben- und Achtringen aus acyclischen Vorstufen. In letzter Zeit hat sich auserdem ihre Nutzlichkeit bei der Totalsynthese komplexer Naturstoffe verwiesen.

Intramolekulare Diels‐Alder‐Reaktion vom Typ 2: Synthese und Chemie von Brückenkopf‐Alkenen

Disposable tethers in type 2 intramolecular diels-alder cycloaddition reactions. Applications in stereochemical control

Reversal of regiospecificity in the kinetic vs. thermodynamic enolization of bicyclic ketones. Direct bridgehead functionalization of the bicyclo[5.3.1]undecane ring system

Application of pericyclic reactions to the synthesis of strained molecules. Intramolecular Diels-Alder cycloadditions. The synthesis of a (Z,Z)-bicyclo[4.3.1]deca-1,6-diene

K. J. Shea

Papers

Application of pericyclic reactions to the synthesis of strained molecules. Intramolecular Diels-Alder cycloadditions. The synthesis of a (Z,Z)-bicyclo[4.3.1]deca-1,6-diene