Synthesis and Transformations of Urazoles Derived from 7,7‐Dicarboxynorcaradiene: Formation of 2,4‐Dioxohexahydro‐1,3,5‐Triazines by an Unusual Base‐Catalyzed Rearrangement

Abstract

4-Phenyl-l.2,4-triazolinc-3.5-dione (PTAD) or 4-mcthyl-l.2.4-triazolinc-3,5-dione (MTAD) cycloaddition to the 7-cyclohcptatrienecarboxylates gave the endo-urazolcs I . With the 7.7-cyclohcptatrienedicarboxylatcs 5 the urazoles 6 were formed. Dccarboxylation of urazole 6 c led to c,rtdo-l b, showing that steric factors prevcnt formation of the desired exo-1 b isomer. Attempts to isornerize undo-l b and rndo-1 c by base catalysis, afforded after methylation with mcthyl iodide the 2,4-dioxohcxahydro-1,3,5-triazine derivativcs 2a,b. This unusual rcarrangcmcnt also took placc with urazolc 3 leading to 1,3.5-triazine 4. but the urazolcs derived from butadicne and cyclopntadiene did not respond. ' H NMR diffcrentid NOE and X-ray analysis of 2b and 6c were necessary for the structural elucid:rtion of the 1.3.5-triazines 2a, b.In our synthetic utilization of triazolinedione adducts ') we required the hitherto unknown urazole 1 with an exocarboxylic acid substituent. However, cycloaddition of 4-phenyl-l,2,4-triazolin-3,5-dione (PTAD) to 7-(methoxycasbonyl)-l,3,5-~ycloheptatriene afforded exclusively the urazole endo-1 b'). In attempt to equilibrate the ester endo-1 b into its isomer exo-lb by base-catalyzed reaction with a strong base like lithium diisopropylamide (LDA), the ester endo-1 b was recovered. To test whether deprotonation of the exo-cyclopropane hydrogen in the ester endo-1 b had indeed taken place, but reprotonation occurred exclusively from the exo side, the LDA treated reaction mixture of ester endo-1 b in THF at -78 "C was allowed to react with methyl iodide under these conditions. Much to our surprise, the unusual rearrangement product 2a was obtained in 21% yield. The NMR spectral data clearly revealed N-methylation, aH = 3.25 and aC = 31.81. Also, the 'H-differential NOE spectroscopy exhibited enhancements of the N-methyl signal when the 11-H and 10-H protons were irradiated and vice versa. The unequivocal structure assignment rests, however, on X-ray analysis. For this purpose the derivative 2 b had to be prepared (isolated in 22% yield), using 4-methyl-

Development of Domino Processes by Using 7‐Silylcycloheptatrienes and Its Analogues

“…Treatment of 15 with lithium diisopropylamide (LDA) thus provided 2,4-dioxohexahydro-1,3,5-triazine 19 in 45 % yield, likely as a result of the unusual base-catalyzed rearrangement [30] depicted in Scheme 7. Treatment of 15 with lithium diisopropylamide (LDA) thus provided 2,4-dioxohexahydro-1,3,5-triazine 19 in 45 % yield, likely as a result of the unusual base-catalyzed rearrangement [30] depicted in Scheme 7.…”

“…Base‐mediated ring opening was also tested as a potent strategy to desymmetrize tetracyclic systems such as 15 . Treatment of 15 with lithium diisopropylamide (LDA) thus provided 2,4‐dioxohexahydro‐1,3,5‐triazine 19 in 45 % yield, likely as a result of the unusual base‐catalyzed rearrangement30 depicted in Scheme .…”

Catalytic, Asymmetric Dearomative Synthesis of Complex Cyclohexanes via a Highly Regio- and Stereoselective Arene Cyclopropanation Using α-Cyanodiazoacetates

“…NCDs readily engage activated dienophiles in [4+2]-cycloadditions . Indeed, [4+2]-cycloadditions of NCD 3c in brine under microwave heating offered access to cycloadducts 8 and 9 (Scheme b).…”

“…NCDs readily engage activated dienophiles in [4+2]cycloadditions. 23 Indeed, [4+2]-cycloadditions of NCD 3c in brine under microwave heating offered access to cycloadducts 8 and 9 (Scheme 3b). The poor yield of the maleic anhydride cycloadduct 8 can be understood in light of significant rearomatization and maleic anhydride hydrolysis that transpired during the reaction.…”

Kinetic Separation and Asymmetric Reactions of Norcaradiene Cycloadducts: Facilitated Access via H2O-Accelerated Cycloaddition

“…21 Hetero-Diels−Alder reactions also proceeded with the norcaradiene isomer of 1a. Treating 1a with 4-phenyl-1,2,4triazoline-3,5-dione (PTAD) in tetrahydrofuran provided complete conversion to the desired adduct 5a in under 60 s. 22 Photochemically generated singlet oxygen 23 smoothly afforded the endoperoxide 6a in 7 h; however, this product was challenging to isolate when the reaction was further scaled as prolonged irradiation of 7a resulted in homolysis of the O− O bond and subsequent cyclization with the pendent alkene to provide the syn-bis-epoxide 8a. 24 Productive reactivity with less reactive dienophiles (acrylates, acroleins, fumarates, etc.)…”