Tricyclic acrylate synthesis

Fraser-Reid s stereocontrolled synthesis of the Woodward reserpine precursor 195 relied upon a tandem 5-exol6-exo radical cyclization of pyranose-derived dienes [76-77]. As outlined in Scheme 36, a,P-unsaturated ester 188 was prepared by free radical coupling of iodide 187 with a tin acrylate. After hydrolysis of 188 (MeONa, MeOH, 100%) to give primary alcohol 189, the silicon tethered diene 190 was installed by silylation. Treatment of 190 with n-BujSnH led to the desired cage molecule 192 in high yield via a 5-exo-trig cyclization to intermediate 191 followed by a 6-exo cyclization. Tamao oxidation of tricycle 192 led to diol... 

Styrene, ethyl acrylate and fumaronitrile have been used to mask (3S)-pentacyclic nitrone 77. After a suitable elaboration of isoxazolidines 78 affording 79, the nitrone moiety was restored by thermally induced cycloreversion (145-180 °C), and the tricyclic intermediate 80 was obtained directly through intramolecular 1,3-DC (31-84% yield). This approach was applied to the synthesis of stereodifferentiated polyhydroxyindolizidines such as 81 <02EJO1941>. 

Some terminal alkenes are oxidized to aldehydes depending on their structure. As described before, acrylonitrile and acrylate are oxidized to acetals of aldehydes in alcohols or ethylene glycol.Selective oxidation of terminal carbons in 4-hydroxy-1-alkenes (18) gave the five-membered hemiacetals (19), which can be converted to y-butyrolactones by PCC oxidation (Scheme 4). Formation of a tricyclic six-membered hemiacetal (62%) from a 5-hydroxy-1-alkene system was used for the synthesis of rosa-ramicin. Formation of aldehydes as a major product from terminal alkenes using (MeCN)2Pd(Cl)(N02) and CuCU in r-butyl alcohol under selected conditions was reported. The vinyl group in the -lactam was oxidized mainly to the aldehyde as shown below (equation 12). ... 

Angew. Chem. Int. Ed. Engl. 44, 3668-3688, 2005 Kent, M. and Tepe, J.J., One-pot Friedel-Crafts/ Robinson-Gabriel synthesis of oxazoles using oxazolone templates, J. Org. Chem. 70, 4211 213, 2005 Movassaghi, M. and Ondrus, A.E., Enantioselective total synthesis of tricyclic myrmicarin alkaloids, Org. Lett. 7, 4423 426, 2005 Paizs, C., Katona, A., and Retey, J., The interaction of heteroaryl-acrylates and alanines with phenylalanine ammonia-lyase form parsley. Chemistry 12, 2739-2744, 2006. Cuprous ions have been observed to promote a Friedel-Crafts acylation reaction (Kozikowski, A.P. and Ames, A., Copper(l) promoted acylation reactions. A transition metal-mediated version of the Friedel-Crafts reaction, J. Am. Chem. Soc. 102, 860-862, 1980). 

When treated with acrylic acid, bicyclic enamine 195 was converted to the tricyclic vinylogous imide 196, which was then incorporated into the synthesis of the Lycopodium alkaloid annotinine (197) as well as an annotinine degradation product (eq. 42).67... 

Attempted construction of the tricyclic enaminone 506 by reaction of 503 with acrylonitrile or methyl acrylate failed, but simple heating of 503 with acrylic acid gave an excellent yield of 506. The reaction was assumed to go through the intermediates 504 and 505 and was used in the synthesis of the Lycopodium alkaloid annotinine 507, Scheme 136 (69CJC433). 

The known 7-e carboxylic acid 506, obtained by the condensation of acrylic acid with furan, was used as a substrate for synthesis of validamine, (510) a component of validamycin antibiotics. The treatment of 506 with hydrogen peroxide in formic acid gave the tricyclic compound 507, which after reduction and hydrolysis afforded cyclitol. Treatment of 508 with 2,2-dimethoxy-propane in the presence of an acid gave a mixture of diisopropylidene derivatives in which compound 509 was predominant. Introduction of an amino group, by way of a tosyl ester and azide displacement, followed by hydrogenation and hydrolysis, completed the synthesis of DL-val-... 

Environmentally benign synthesis routes for umbelliferone (I), 7-hydroxy-4-methylcoumarin (II), 3,4-dihydrocoumarin (III), and tricyclic coumarin (IV) (Figure 10.2) were developed using zeolite-H-p or Amberlyst-15 as solid catalysts. This resulted in the minimization of harmful mineral acid wastes. The reactions of resorcinol with acrylic acid, propynoic acid, and ethyl acetoacetate were investigated in toluene and p-chlorotoluene under reflux conditions to obtain coumarins in 60%-80% yield (Hoefnagel et al. 1995 Gunnewegh et al. 1995). 

A variant in the production of an intermediate in the Robinson synthesis, the tricyclic ABC diketone (18), was developed by Banerjee and co-workers [635, 636] (Scheme 58). The triester (22) was obtained from a-ethoxycarbonylcyclohexanone (21) by the Michael reaction with methyl acrylate, alkaline cleavage, and esterification, and it was then cyclized by Dieckmann s method with subsequent bromination and dehydrogenation to give the unsaturated keto diester (23). The addition of cyanoacetic ester gave compound (26) from which the keto triester (25) was obtained by methylation, acid hydrolysis, and esterification. The latter, by Dieck-mann cyclization and hydrolysis, gave the BC fragment (24). Selective ketalization, reduction, and hydrolysis of the ketal led to the hydroxy-ketone (27). The trans-B/C linkage present in it required the protection... 

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