A s y m m e t r i c C o n s t r u c t i o n o f t h e A z a s p i r o [ 5 . 6 ] d o d e c -9 -e n e S y s t e mAbstract: The asymmetric formation of azaspiro[5.6]dodec-9-ene system is described. The Diels-Alder reactions of an a-methylene caprolactam and diene in the presence of a Cu(II) and (S,S)-tBu-BOX complex afford the desired spirocyclic compounds with good exo-selectivity as well as excellent enantioselectivity. These exoadducts would be applicable to the synthesis of marine natural toxins including the corresponding cyclic imine moiety.Recently, a new class of marine toxins containing an azaspiro[5.6]dodec-9-ene moiety has been isolated from shellfish and dinoflagellate, such as pinnatoxins 1 and pteriatoxin 2 (Figure 1). The toxicological properties of these compounds seem to be attributed to the cyclic imine moiety, which would be biogenetically constructed by an intramolecular Diels-Alder reaction via exo-addition. Several groups have investigated the synthesis of these attractive target molecules. 3,4 Our strategy in the construction of the azaspirocyclic moiety is an asymmetric DielsAlder reaction of a-methylene caprolactam and diene utilizing chiral Lewis acid (Scheme 1). We selected (S,S)-tBuBOX/Cu complex reported by Evans 5 as a chiral Lewis acid in Diels-Alder reaction considering that carbamate lactam, such as 1, would be applicable to the asymmetric construction of a spirocyclic system due to the nature of its locked s-cis conformation. 6 Herein we describe the asymmetric formation of azaspiro[5.6]dodec-9-ene, which is supposed to be the common synthetic key intermediate for pinnatoxin and pteriatoxin, since the conversion of lactam to imine have been known well. 7The a-methylene caprolactam derivative was readily prepared by the following sequence (Scheme 2). N-CBZ protected e-caprolactam 2 was converted to the silyl ketene acetal 3, which was subjected to the reaction with Eschenmoser's salt and the subsequent treatment with MeI on heating to furnish a-methylene-lactam 4. 8 At first, the Diels-Alder reaction of 4 with cyclopentadiene in the presence of a Cu(II) and (S,S)-t-Bu-BOX complex was investigated (Scheme 3). The reaction of 4 and cyclopentadiene in the presence of (S,S)-t-BuBOX, Cu(OTf) 2 , and MS-3Å at 25 °C for 6 h afforded the corresponding spirocyclic adducts with good enantioselectivity. This result indicates that the a-methylene lactam could coordinate the copper/t-Bu-BOX complex to form the preferential intermediate. In other words, it could support the proposal of s-cis conformation of the dienophile in the activated complex. It should be noted that the slight exoselectivity (exo/endo = 1.6:1) was observed in this case. Roush and other groups have found that the Diels-Alder reaction of conformationally rigid cyclic cisoid dienophiles, such as a-methylene-lactone, with cyclopentadiene proceeds with exo-selectivity accounting for by Berson's dipole moment hypotheses. 9,10
Construction theories and examples for method of powerfully chucking the tip of existing pile at removal of existing piles Shuichi KUWAHARA 1 ,Shin-ichi HAMAGUCHI 1 ,Yoshikatsu SHIMADA 1 ,Shinya INAZUMI 2 1 Japan Association for Pulling-out Existing Piles (JAPEP)
Conversion of Prelaureatin into Laurallene, a Bromo-Allene Compound, by Enzymatic and Chemical Bromo-Etherification Reactions.-The (E) isomer of prelaureatin is found to react with 2,4,4,6-tetrabromo-2,5-cyclohexadienone and NaBr/H2O2/lactoperoxidase to afford laurallene (II). Starting from the (Z) isomer (deuterated form) laurallene (II) is not formed or in very small amounts. -(ISHIHARA, J.; SHIMADA, Y.; KANOH, N.; TAKASUGI, Y.; FUKUZAWA, A.; MURAI, A.; Tetrahedron 53 (1997) 25, 8371-8382; Div. Mol. Chem., Grad. Sch. Eng., Hokkaido Univ., Sapporo 060, Japan; EN)
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