Tricyclic acrylates

Compound 3, the first highly active tricyclic acrylate to be made, was prepared on a 0 4 mol scale for field trials by the pathway shown in Figure 6. An Ullmann ether coupling was the key step in the construction of the intermediate phenoxyphenoxyphenylacetate 5 which was then converted stereospecifically into 4 via Claisen condensation with methyl formate followed by 0-methylation of the resulting P-hydroxyacrylate. 

For the construction of the I ring, the vinylic group introduced to activate the y-hydroxy epoxide moiety of 28 towards cyclization is an acrylic ester residue, which concomitantly allows cyclization on the allylic position, with formation of the tricyclic compound 29 containing the IJK fragment of the natural product, and fur-... 

The de Meijere group [63] prepared interesting spiro-compounds containing a cyclopropyl moiety using a combination of a Heck and a Diels-Alder reaction, with bicyclopropylidene 6/1-115 as the starting material. The transformation can be performed as a three-component process. Thus, reaction of 6/1-115, iodobenzene and acrylate gave 6/1-116 in excellent yield. With vinyliodide, the tricyclic compound 6/1-117 was obtained (Scheme 6/1.31). Several other examples were also described. 

It is well known that the use of a synthetic equivalent of azomethine ylide, the thiazolium ylide, a known synthon for the simple azomethine dipole, undergoes cycloadditions with higher regioselectivity than the parent ylide <1994JOC4304, 1994JOC2773>. In order to control the enantioselectivity of the reaction, an Evans oxazolidionone was incorporated into the acrylate dipolarophile as in Scheme 71. The cycloaddition was carried out by reaction of 4 equiv of the acrylate with the thiazolium salt to afford the diastereomeric tricyclic adduct 27 (Scheme 71) <2002BMC3509>. 

The application of the one-pot Ugi four-component reaction by stirring a mixture of the aldehyde 486, benzyl amine 487, isocyanide 479, and acrylic acid 385 in methanol at room temperature for 36 h afforded the triene 488 as a 74 26 mixture of amine rotational isomers in 80% combined yield. The triene 488 on heating in DMSO at 120 °C for 12 h underwent cycloaddition to give the tricyclic compound 489 as a single diastereomer in 98% yield (Scheme 111). 

Pyranopyrroloimidazoles have been prepared stereospecifically by an intramolecular 1,3-dipolar cycloaddition reaction. Either enantiomer of the imidazoline derivative 176 (the -enantiomer is shown) may react with the bromoacetyl-containing acrylate dipolarophile 177, in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), to give the diastereomerically pure tricyclic product 178 in moderate yield (Equation 15). This reaction involves quaternization of the imidazole N, reaction of the quaternary salt with base to give the 1,3-dipole, which can then react, intramolecularly and stereospecifically, with the tethered dipolarophile <1997TL1647>. 

A tandem radical addition/cyclization process has been described for the formation of benzindolizidine systems from l-(2-iodoethyl)indoles and methyl acrylate <00TL10181>. In this process, sun-lamp irradiation of a solution of the l-(2-iodoethyl)ethylindoles 149 in refluxing benzene containing hexamethylditin and methyl acrylate effects intermolecular radical addition to the activated double bond leading to the stabilized radical 150. Intramolecular cyclization to the C-2 position of the indole nucleus then affords the benzindolzidine derivatives 151 after rearomatization of the tricyclic radical. 

The very good yields of especially the bridgehead alkoxy derivatives 231 and the excellent regioselectivity with which they can be transformed to other skeletons plus the fact that a spirocyclopropane moiety is a mimic of and can in fact be considered as a masked gem-dimethyl substituent [28, 112] makes these products versatile precursors of certain natural products. In fact, one may conceive new approaches to the total syntheses of taxol [113-115] and of mediter-raneol [116]. Both strategies rely on the MIMIRC reaction of lithium cycloalka-dienolates [117] with the a-chloro acrylate 1-Me to produce a tricyclic precursor to the appropriate bicyclo [n.2.1]alkanedione derivative, which are key structural units of several diterpenes and their metabolites. 

Further studies on the 1,3-dipolar cycloadditions of these molecules (86) have been reported. Addition of allyl alcohol gives endo adducts (505) which are not isolated but spontaneously cyclize to tricyclic products (506). Similar tricyclic products were also obtained using A-allylbenzenesulfonamide, triethylammonium acrylate, and vinylpyridines as dipolarophiles. It has previously been shown that the pyridinium-3-olates with chloroketenes (RCC1=C=O) give 2-oxofuro [2,3-c] pyridine 507 (see p. 22). Further studies demonstrate that when bromoketenes (RCBr=C=O) are used as dipolarophiles, a mixture of 2-oxofuro[2,3-c]pyridines (507) and isomeric... 

Vinyltriazolines are unique thermolysis leads to high yields of 1-vinylaziridines. This is true of fused-ring tetracyclic (Scheme 40)199,201 and tricyclic triazolines (Schemes 42 and 43)200 204 with vinylic substitution in the 1-position. 1-Vinyltriazoline with no substituents on the ring carbons furnishes 1-vinylaziridine without formation of pyrrolines.378 Thermal decomposition of vinyl azides in acrylic acid derivatives is a synthetic route for 2-substituted 1-vinylaziridines.470 Similarly, aziridine 1-oximes are the only products of thermolysis of triazoline 1-oximes.107... 

JHC559). When 2-phenylpyridopyrimidine-3-acrylate 629 (R = Ph) was added to refluxing Dowtherm A and the reaction period was 5 hours, 1,8-naphthyridine-3-acrylate 630 (R = Ph) and 2//-pyrano[3,2-c][l,8]naphthyridin-2-one 631 (R = Ph) were prepared in 70% and 1.7% yields, respectively. 2-Piperidinopyridopyrimidine-3-acrylate 629 (R = piperidino) afforded 1,8-naphthyridine-3-acrylate 630 (R = piper-idino) and tricyclic 631 (R = piperidino) in 63% and 15% yields, respectively, when the reaction period was 20 minutes. After 90 minutes, only... 

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... 

Aldehyde 346 gave a mixture of tricyclic 347 and tetracyclic derivatives 348 on the action of TFA followed by treatment with Et3N and (Bu acrylate [07H(72)385]. When the oxidation of tricycle 347 was promoted by adding TEMPO the unsaturated cycloadduct 348 was the only product. Tricycles 347 could be transformed into tetracycle 348 by treating with NBS followed by treatment with Et3N and (Bu acrylate in 35% yield. 

Furo[3,4-(/]pyrimidines are ideally suited for participation in Diels-Alder reactions. The reaction of the derivatives (47) with dienophiles leads to tricyclic compounds of the type (48) <9iJOC245>. There is some selectivity, since methyl acrylate forms only two regioisomeric endo products whilst other dienophiles yield both endo and exo adducts (Equation (13)). 

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>. 

Vinylbenzo[7]furans, 3-vinylfuropyridines, and 3-vinylindoles were employed as conjugated dienes in the Diels-Alder reaction with ethyl acrylate, affording tricyclic adducts in fair to good yields, as shown in Equation (103) <20020L2791>. 

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). 

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