Hydroxy enol ethers, cyclization

Stevens and co-workers have also attempted to develop a fundamentally different approach to the tricyclic amino ketone 463 which is used in the Fischer cyclization approach to the Aspidosperma skeleton (240). Condensation of the aldehyde-ester 553 with protected keto amine 554 gave an imine (555) which, upon heating with ammonium chloride at 160°, afforded the 2-pyrroline ester 556 in 70% yield. Treatment with dry hydrochloric acid gas in ether was followed by acid hydrolysis of the ketal, and base-catalyzed cyclization produced a mixture of two enol ethers (557 and 558) the latter predominating. The major isomer was reduced with lithium aluminum hydride and the hydroxy enol ether dehydrated in hot... 

The plausible mechanism of the reaction is shown in Fig. 25. The reaction probably proceeds through the activation of imine (formed in situ from the o-hydroxy benzaldehyde and the aromatic amine) by the catalyst followed by the addition and subsequent cyclization of the enol ether, resulting in the formation of the fused acetal. Ionic liquids are stable enough with amines and water and also effectively activate the imines to undergo cyclization. The recovered ionic liquid can be re-used with gradual decrease in the efficiency of the method. The hydro-phobic nature of the ionic liquid also helps in recovery of the catalyst. 

Treatment of l-acyl-3-amino-5-pyrazolones (417) with an equimolar amount of an enol ether, such as ethoxymethylenecyanoacetate or ethoxymethylenemalononitrile in DMSO at 70-80 C for 3 h furnishes pyrazoleacrylonitriles (418) in good yields. The use of other solvents decreases the yields considerably. Heating the intermediates (418) in diphenyl ether at 200 °C promoted cyclization to give 2-acyl-6-amino-3-hydroxy-2//-pyrazolo[3,4-b]pyridines (419) (Scheme 47) <94JHC925>. 

Snider has shown that thermolysis of 2,6-dimethyl-2,7-octadienal at 350°C yielded three compounds, 365-367, having the iridoid skeleton. The lactone 368 was made by cyclization of the corresponding hydroxy acid ( 8-hydroxy-citronellic acid ), and its tert-butyldimethylsilyl enol ether rearranged in an Ireland-type Claisen rearrangement, yielding the iridoid acid 369 after removal of the silyl group with HF in acetonitrile. The latter was converted (by hydrobora-tion-oxidation) into both isomers of dihydronepetalactone (370) (erroneously considered to be unsynthesized by the authors, who clearly did not read Vol. 4, p. 497). Iridomyrmecin (371) is also accessible from 369 (Scheme 30). 

Cyclizations. Cyclization on elimination of a dithioacetal unit simultaneous with a thioester carbonyl by Cp2Ti[P(OEt)j]2, leads to 2,3-dihydrothiophenes. The analogous reaction of to-alkanoyloxyalkanal bis(phenylthioacetals) gives (o-hydroxy ketones due to hydrolysis of the cyclic enol ether products. ... 

Zinnes and co-workers prepared pyrido[l,2-b][l,2]benzothiazines (Scheme 8) 1,2-benzothiazine 182 with isopropyl iodide and potassium carbonate resulted in spontaneous aldol cyclization of the intermediate enol ether 183 to 7,8-dihydro-8-hydroxy-ll-isopropyloxy 8-substituted pyrido[l,2-b][l,2]benzothiazin-10(9//)-one 5,5 dioxide (184). In sulfuric acid, dehydration and ether cleavage of 184 gave the corresponding unsaturated )3-diketone 185. Hydrogenation gave the saturated analogs 186. An attempt to prepare 186 directly by base-catalyzed cyclization of 187 afforded a high yield of 2,3-dihydro-6/f-oxepino [3,2-c][l,2]benzothiazin-5(4H)-one 7,7-dioxide (188) (Eq. 39). 

Treatment of pristinamycin IIa with meta-chloroperbenzoic acid afforded a compound to which the structure (79) was initially assigned, resulting from epoxidation of the more substituted double bond (12,13-C). This material did not display chemical properties characteristic of an epoxide as the assumed epoxide moiety remaining after treatment with nucleophilic reagents. Michael-type addition products on the dehydroproline ring were observed after treatment with thiols or amines (see Sect. 5.4.5). 2D-NMR analysis of the product from reaction of pristinamycin IIa with mCPBA showed that a transannular oxidative cyclization had taken place leading to formation of (80). The reaction can be considered to involve initial epoxidation of the 12,13-double bond followed by an intramolecular nucleophilic attack by the 37-hydroxy of the enol ether (Scheme 19). A similar transannular oxidative cyclization reaction has been reported for the reaction of l,5-dimethylcyclooct-4-en-l-ol with meta-chloroperbenzoic acid [125]. 

Highly functionalized tetrahydropyran-4-ones can be obtained through a silyl enol ether Prins cyclization promoted by a condensation reaction of hydroxy silyl enol ethers with Lewis-acid-activated aldehydes, with high diastereoselectivity (14JOC8733). Spirooxindole tetrahydropyran-4-ones are obtained from oxa-DA reaction of acyclic a,P-unsaturated methylke-tones and isatins mediated by a bifunctional enamine-metal Lewis acid catalyst, in good yields and moderate stereoselectivities (14S1339). 

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