Stereospecific intramolecular-Diels-Alder cycloaddition

This reaction probably involves ring opening to the o-xylylene followed by an intramolecular Diels-Alder cycloaddition. The stereospecificity probably results from a conrotatory ring opening with outward rotation of the side chain to generate a transoid diene system which undergoes the cycloaddition as shown in Scheme 14.10. 

The application of intramolecular dipolar cycloaddition reactions to the synthesis of complex natural products has recently come to be recognized as a very powerful synthetic tool, one equally akin to the intramolecular Diels-Alder reaction in its potential scope of application.69 This is particularly the case with nitrile oxides and the 1NOC reaction has been extensively utilized in total synthesis.70 The intramolecular nitrile oxide cycloaddition (INOC) generally displays exceptional regio- and stereo-chemical control which undoubtedly accounts for the popularity of this reaction. Internal cycloadditions of nitrile oxides have been found to offer a powerful solution to many problems in complex natural product synthesis.48 For example, Confalone and coworkers have utilized the INOC reaction for the stereospecific synthesis of the key amino alcohol (60), which was converted in five subsequent steps to ( )-biotin (61 Scheme 14).71... 

For A-acyliminium ions that (can) adopt the s-cis conformation, the mechanistic picture is quite different. Now the /V-acyliminium intermediate reacts as a 4ir-electron component in a Diels-Alder cycloaddition with inverse electron demand (equation 28). " This process also shows high regio- and stereo-selectivity in most cases. A nice illustration of high stereospecificity is found in recent work on the intramolecular Diels-Alder reaction of A-acyliminium species (equations 29 and 30). The bis-amides (50) and (51) serve as precursors to the reactive intermediates, which cycloadd to the alkenes with high selectivity to give r/a s-fused bicyclic 5,6-dihydro-1,3-oxazines. 

From the above survey of results the synthetic potential of the oxazinolactam intermediate 46 in hand, we envisaged to synthesize monomorine I (62) which constitutes of an extension of the methodology based on intramolecular nitroso Diels-Alder cycloaddition. The relative stereochemistry of this substance, isolated as one of the trail pheromones from Pharaoh ants (Monomorium pharaonis L.) (ref. 19), has been determined its relative stereochemistry by nonstereoselective synthesis (ref. 20). More recently, a stereospecific synthesis of racemic 62 (ref. 21) and a chiral synthesis of the (-)-enantiomer of natural 62 (ref. 22) were reported. 

Hydrindanes can be synthesized from l,8-dien-3-ynes by [4+2] cycloaddition [30, 219]. However, l,3-dien-8-ynes undergo intramolecular Diels-Alder reactions to give formal [4+2] products or hexahydropentalene compounds [224, 225]. The reaction of cyclopropylenynes gives pentalenes via Prins cyclization (Scheme 1.32) [174]. Due to the lack of stereospecificity in the reaction, anon-concerted opening of the cyclopropyl gold carbene to an open carbocation is proposed. 

Since its initial discovery in 1928," the Diels-Alder reaction has become one of the most powerful transformations at the disposal of organic chemists and has found applications in countless occasions. This popularity of the Diels-Alder reaction stems from its ability to stereospecifically generate a six-membered ring through the formation of two new CT-bonds, one 7t-bond, and up to four stereocenters in one concerted cycloaddition. The Diels-Alder reaction is well suited for transannular applications because the dienes and dienophiles can be easily incorporated into macrocyclic precursors and the reaction can be accelerated by catalysts or by heating alone. In addition, the macrocyclic environment provides both enthalpic and entropic activation for reactions that may not readily occur under intermolecular or other intramolecular settings. This allows for efficient generation of complex polycyclic compounds from relatively simple macrocyclic substrates. ... 

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