Azido-ketones rearrangement

There are several synthetic approaches that rely on a molecular rearrangement to incorporate the appropriate functionality. A classical reaction is the Curtius rearrangement,i43 in which an azido ketone rearranges to an isocyanate. Subsequent hydrolysis converts the isocyanate to an amine. This approach can be applied to the synthesis of amino acids. When 2,2,3,3-tetramethylbutanedioic acid (L249) was... 

The obtained spiro keto esters 2-181 could be converted into 2-183, employing among other transformations an intramolecular Schmidt rearrangement [101] of the azido ketones 2-182. 

Schmidt rearrangement of an azido ketone. Thus, 6,7-dimethoxy-2-tetralone (219) has been reacted with methyl ( )-7-iodo-2-heptenoate (220) affording stereoselectively the Cl-spiroketone 221 in 48% yield. After transformation of the latter to the azido derivative 222 the tetracyclic lactam 223 was obtained under ring expansion possessing the schelhammeridine core. Finally, LiAlH4 reduction smoothly provides the ( )-3-demethoxy-l,2-dihydrocomosidine base 224 (772) (Scheme 41). 

Benzisoxazoles.—The reaction of salicylaldehyde oxime with thionyl chloride in pyridine to yield 1,2-benzisoxazole (539 R = H) constitutes a new synthesis of this ring system.Thermolysis of the azido-ketone (540) affords the linearly annelated anthranil (541). ° The benzisoxazoles (539 R = H, Me, or Ph) rearrange photochemically to the benzoxazoles (543) via intermediate azirines (542). ° Irradiation of an aqueous solution of the benzisoxazolium salt (544) gives the phenolic ketone (545). ° ... 

The thermolysis of 4-azidophenyl methyl ketone in morpholine at 170°C yields a mixture of the expected 5-acetyl-2-morpholino-3f/-azepine (33) and 6-acetyl-2-morpholino-3//-azepine (34), the product of a unique and totally unexpected thermal rearrangement of the 5-acetyl derivative.119 Similar results can be obtained in hot piperidine, whereas thermolysis of 4-azido-diphenyl ketone under similar conditions yields only the 6-benzoyl-2-(cycloalkylamino)-3//-azepines (7-18%) accompanied by much tar. 

FORMATION AND PHOTOCHEMICAL WOLFF REARRANGEMENT OF CYCLIC a-DIAZO KETONES D-NORANDROST-5-EN-3 -0L-16-CARB0XYLIC ACIDS, 52, 53 FORMIC ACID, AZIDO—, tert-BUTYL ESTER, 50, 9 Formylation, with acetic formic anhydride, 50, 2 p-FORMYLBENZENESULFONAMIDE, ... 

Amides lactams. Dimethyl thioketals of cyclic or acyclic ketones react with iodine azide to form an a-azido sulfide in 75-95% yield. The product rearranges to an amide or a lactam in high yield in the presence of trifluoroacctic acid. This sequence is an attractive alternative to the Beckmann rearrangement or Schmidt reaction. 

Aube and co-workers have found that enolizable ketones react with benzyl azide in triflic acid to yield /V-(phenylamino)-methylated products [Eq. (5.354)]. The transformation is an aza-Mannich reaction interpreted with the involvement of the Mannich reagent A -phenyl iminium ion 295 formed in situ in a Schmidt rearrangement. Cyclic tertiary alcohols react with alkyl azides in triflic acid to yield N-alkylamines (296, 297)983 [Eq. (5.355)]. The Schmidt rearrangement was used to transform Merrifield resin into amino-polystyrene resin by reacting the azido derivative in excess triflic acid (CH2CI2, 0°C).984... 

The intramolecular reaction of ketones with alkyl azides is quite general in terms of the ketone moiety, but the distance between the carbonyl group and the azide moiety is critical. Thus, a good yield of lactam 6 is formed with a span of four carbons between the carbonyl and the azido group, and in contrast, no rearrangement occurs with a span of either three or five carbons. 

Acyclic ketones and aldehydes having 3 or 4 carbon atoms between the azido and carbonyl group also undergo rearrangements to afford A-substituted lactams when treated... 

Murphy and coworkers have also reported rearrangement reactions of azido-tethered epoxides in which the azide tether was attached directly to a phenyl-substituted epoxide. Thus, when they treated epoxide 36 with SnCLt at 0°C in THE, ketone 37 was isolated... 

An effective way for introduction of a variety of heterocyclic fragments in the position 7 of the fluoroquinolone skeleton is the methodology of 1,3-dipolar cycloaddition reactions [164-167]. Indeed, the reaction of 7-azido derivative of 6-fluoroquinolone 39 with enamines of cyclic ketones and norbomene proceeds rather smoothly with the formation of the corresponding exo-l,2,3-triazolines 40 which undergo the cationic rearrangements into amidines 41 or aminonorbomane 42 [164, 165]. 7-Azido derivatives 39 are capable of reacting with heterocyclic amines to form new 7- fluoroquinolones (Scheme 20) [168]. 

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