Rearrangements lithium diisopropylamide

There are some recent examples of this type of synthesis of pyridazines, but this approach is more valuable for cinnolines. Alkyl and aryl ketazines can be transformed with lithium diisopropylamide into their dianions, which rearrange to tetrahydropyridazines, pyrroles or pyrazoles, depending on the nature of the ketazlne. It is postulated that the reaction course is mainly dependent on the electron density on the carbon termini bearing anionic charges (Scheme 65) (78JOC3370). 

Interestingly, treatment of bicyclic imidate 5 (R = OMe) with lithium diisopropylamide at — 78 C, followed by addition of iodomethane and quenching into ammonium chloride solution, gives 2-methoxy-3-methyl-37/-azepine. In the absence of iodomethane, 2-methoxy-3i/-azepine (6, R = OMe) is produced. Rearrangement of the lithiated bicycle to a lithiated 2-methoxy-3//-azepine, followed by regioselective trapping by the electrophile, is the most likely mechanistic rationale. 

Further variations of the Claisen rearrangement protocol were also utilized for the synthesis of allenic amino acid derivatives. Whereas the Ireland-Claisen rearrangement led to unsatisfactory results [133b], a number of variously substituted a-allenic a-amino acids were prepared by Kazmaier [135] by chelate-controlled Claisen rearrangement of ester enolates (Scheme 18.47). For example, deprotonation of the propargylic ester 147 with 2 equiv. of lithium diisopropylamide and transmetallation with zinc chloride furnished the chelate complex 148, which underwent a highly syn-stereoselective rearrangement to the amino acid derivative 149. 

Scheme 18.47 Synthesis of the allenic amino acid derivative 149 by chelate-controlled Claisen rearrangement [135] (LDA= lithium diisopropylamide Cbz = benzyloxycarbonyl).

CLAISEN REARRANGEMENT Alkylaluminum halides. Lithium diisopropylamide. Potassium hydride. Sodium dithionite. Titanium(TV) chloride. Trifluoroacetic acid. Trimethylaluminum. 

The role of aggregates and mixed aggregates on the lithium diisopropylamide-mediated anionic Fries rearrangements of aryl carbamates (Scheme 7) has been described.57 Substituents at the meta -position of the arene (X = H, OMe, F) and the... 

The reaction of pure diastereomer 284 in the presence of 2 equiv of lithium diisopropylamide (LDA) led to the stereospecific formation of the hydroxyphenyldiazaphospholidine oxide 285 in 94% yield. When the reaction was performed with 8equiv of LDA, it produced l,5,2-diazaphosphepin-2-oxides 286 in 89% yield. The reaction proceeds via two diastereoselective 1,3-migration rearrangements, and a stereospecific ring expansion <1999AGE1479>. 

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