Tricyclic compounds, cyclization

Unlike the intermolecular reaction, the intramolecular aminopalladation proceeds more easily[13,14,166], Methylindole (164) is obtained by the intramolecular exo amination of 2-allylaniline (163). If there is another olefinic bond in the same molecule, the aminopalladation product 165 undergoes intramolecular alkene insertion to give the tricyclic compound 166[178]. 2,2-Dimethyl-l,2-dihydroquinoline (168) is obtained by endo cyclization of 2-(3,3-dimethyiallyl)aniline (167). The oxidative amination proceeds smoothly... 

The smooth intramolecular nucleophilic displacement of biphenyl carboxylic acids leading to benzocoumarins (See Section II.A.) inspired also investigation of the behavior of similar diphenyl ether, diphenyl sulfide and A-methyldiphenyl amine derivatives 458 under similar conditions. However, all these attempts to achieve cyclization to tricyclic compounds 459 were unsuccessful, probably due to the unfavorable stereochemistry for the formation of the required seven-mem-bered transition states and also to the presence of the deactivating bridge groups X (Eq. 42) [68JCS(C)1030]. 

Reaction of aniline derivatives with 4-chlorobutyroyl chloride followed by cyclization with sodium ethoxide and subsequent thionation promoted by sonication gave the corresponding A -arylpyrrolidine-2-thiones 126. Zinc-mediated condensation of diethyl bromomalonate with 126 using iodine as activator gave the vinylogous urethanes 127 whose cyclization with PPA gave the tricyclic compound 128 which upon hydrolysis afforded the acid 129 (96TL9403). 

R = Ar) and cyclized tricyclic compound 240 (R = Ar) was obtained when 2-bromoacetophenones were reacted with 8-hydroxyquinolin-2(l//)-one under the above conditions. Presence of a 4-methoxy substituent shifted the equilibrium to the ring-opened product 241 (R = 4-MeOPh), while that of 4-nitro group gave only cyclized product 240 (R = N02). Similarly, mixtures of ring-opened and 2,3,6,7-tetrahydro-5//-pyrido[l,2,3- /e]-l,4-benzoxazin-5-one derivatives were formed in the reaction of 8-hydroxy-l,2,3,4-tetrahydroquinolin-2-one and halomethyl ketones (00HCA349). 

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 diastereosclectivity in this particular cyclization was exploited in a number of direct syntheses of terpenes from the eudesmane type (see Table 2). By this technique tricyclic compounds can be synthesized generating three new asymmetric centers55. 

Tricyclic compounds can be obtained directly by annulation on to cyclic allylsilanes, using either ethylaluminum dichloride or titanium(IV) chloride as Lewis acids57. The stereochemical outcome of this particular cyclization is controlled by the relative configuration of the cyclic allylsilane. The reaction follows the usual anti" SE2 process for reactions of allylsilanes with electrophiles. Thus, the reaction was stereospecific, which makes it very useful for stereocon-trolled syntheses of complex ring systems57. 

Hydantoins have been prepared starting from aminoesters that were first transformed into the corresponding carbanilides (ureas) 144 under standard conditions and then cyclized under microwave irradiation in the presence of Ba(OH)2 in DMF in 2 min and in yields ranging from 91 to 80% (Scheme 51) [91,92], Simple and more complex hi- and tricyclic compounds, such as 145-147, have been prepared with this method that seems versatile and applicable to many substrates. 

Intramolecular alkylation of enolates can be used to synthesize bi- and tricyclic compounds. Identify all the bonds in the following compounds that could be formed by intramolecular enolate alkylation. Select the one that you think is most likely to succeed and suggest reasonable reactants and reaction conditions for cyclization. 

Holzapfel and coworkers [132] used the carbopalladation ofalkynes followed by a cyclization for the synthesis of tricyclic compounds as 6/1-280, derived from the sugar derivative 6/1-279 (Scheme 6/1.74). 

A reductive amination/cyclization strategy was used by Surya Prakash Rao and coworkers to synthesize the annulated tricyclic compounds 10-93 [34]. These authors employed the microwave irradiation of a cis/trans- mixture of 1,5,9-triketone 10-92 with an excess of ammonium formate for 1 min in 87 % yield (Scheme 10.23). 

The reactivity of these tricyclic compounds has been investigated in detail. Reaction of these with sodium cyanoborohydride in acetic acid reduces the imine double bonds to give the tetrahydro-derivatives, for example, 37 gives 39. Reaction of 37 with sodium methoxide results in the ring-opened sulfonate salt 40 re-acidification of this salt gives the corresponding sulfonic acid which cyclizes back to the tricycle 37. Further heating of the sulfonic acid... 

These cyclizations normally involve a carbonyl group. The enamine 109 undergoes a reaction with oxalyl chloride to give an intermediate product 110, which is then cyclized upon treatment with HC1 leading to the angular tricyclic compound 111 in excellent yield (Scheme 11) <1995EJM525>. 

The following unusual cyclization took place by the reaction of p-benzoquinone coordinated by palladium with two moles of butadiene at 60°C to give the tricyclic compound, 128 (117). 

Cleavage of the cyclobutane ring of (277) by Lewis acid followed by cyclization of the allylsilane (278), furnished the tricyclic compound (278)94). 

Scheme 6 Radical tandem cyclization to tricyclic compounds.

This reaction in the presence of base was applied to a tandem cyclization. When bis-alkynyl silyl enol ether 93a was irradiated in toluene in the presence of 10 mol % W(CO)6 and DABCO with 1 equiv of H2O, the expected tricyclic ketone 94a was obtained in 80% yield. The five-membered substrate 93b also gave the corresponding tricyclic ketone 94b having the basic carbon skeleton of the cedranes. Thus we can prepare synthetically useful tricyclic compounds utilizing this W (CO)5(L)-catalyzed tandem cyclization in the presence of DABCO [25c] (Scheme 5.29). 

Alkylation of a ring nitrogen on 1 with an acyl bromide leads to a cyclization reaction producing a tricyclic compound 2 (Equation 1) <2003CHE669>. 

Treatment of the tricyclic compound 133 with tributyltin hydride and 2,2 -azobisisobutyronitrile (AIBN) produces a radical which cyclizes to give 134 creating a new quaternary center (Equation 35) <2002JA2080>. 

The [2+2+2] cyclotrimerization of triynes has been reported using rhodium catalysts <2003JA12143> under biphasic conditions. Thus, the cyclization of triyne 174 proceeds rapidly in a biphasic system to produce the tricyclic compound in good yield using an in t/r -generated water-soluble rhodium catalyst (Equation 108) <2003JA7784>. 

In Delfourne and co-workers study toward the total synthesis of meridine, the Meldrum s acid derivative 91 was prepared. After several unsuccessful attempts to cyclize this material to the desired tricyclic compound 92, it was found that conversion into the quinone 93 was necessary for cyclization to occur (Scheme 4) <1997T1743>. Another approach to compounds with a central six-membered carbocyclic ring using Meldrum s acid derivatives has been... 

Rhodium carbonyl complexes catalyze the silane-initiated cascade cyclization of 1,6,11-triynes to form fused aromatic tricyclic compounds. For example, reaction of 83 [X = G(G02Et)2] with methyldiphenylsilane catalyzed by the tetrarhodium carbonyl cluster Rh4(GO)i2 in toluene at room temperature gave an 88 12 mixture of the silylated and unsilylated fused tricycles 84a and 84b [X = G(G02Et)2] in 85% combined yield (Equation (55)). The ratio of silylated to unsilylated tricyclic product formed in the reaction of 1,6,11-triynes was dependent on the nature of the substrate (Equation (55)). For example, Rh4(GO)i2-catalyzed reaction of diaminotriyne 83 (X = NBn) with methyldiphenylsilane gave unsilylated tricycle 84b (X = NBn) in 92% yield as the exclusive product (Equation (55)). 

The copper mediated cycloisomerisation of alkynyl imines provides a facile access to pyrroles and fused aromatic pyrroloheterocycles.50 In a recent example, shown in 8.39., the pyrrolopyrimidine bearing an acetylene moiety in the appropriate position cyclized smoothly to give the desired tricyclic compound in 89% yield.51... 

Sorm and Beranek39 used an intramolecular acylation in their synthesis of l-azoniumtricyclo[3.3.3.0]undecane (66). Condensation of nitromethane with acrylonitrile in the presence of an alkaline catalyst resulted in the formation of tris-(2-cyanoethyl)nitromethane (60), which afforded the triethyl ester 61 on hydrolysis followed by esterification. The ester was reduced catalytically to give a pyrrolidone (62). The derivative (62) gave rise to 8-(j8-carboethoxyethyl)-3,5-dioxo-pyrrolizidine (63) on heating. Reduction of 63 resulted in the formation of 8-(y-hydroxypropyl)pyrrolizidine (64). Replacement of the hydroxy group by bromine (65), followed by cyclization, afforded the tricyclic compound 66. 

Thermal cyclization of the /3-benzo[6]thienylvinyl isocyanate (30) produces the tricyclic compound (31) in 12% yield (70JHC1191). To the same category belongs the generation of the thieno[2,3-cf]pyrimidines (34) by reaction of N- (2-thienyl)chloroformamidines (32) with NCX- (X = O, S or Se) presumably (33) is the intermediate in this cyclization (80LA699). 

A related reaction is the bromine-induced oxidative cyclization of l-acyI-3-(3-thienyl)-thioureas to 2-acylaminothieno[3,2-d]thiazoles the reaction probably proceeds through the formation of the sulfenyl bromide (Scheme 23) (78JHC81). The corresponding 2-thienyl derivatives, however, gave only bromo substituted products (Scheme 23). A similar cyclization is brought about on treatment of /3-(3-benzo[6]thienyl)-a-mercaptoacrylic acids (129) with iodine in THF, when the tricyclic compounds (130) are formed (70AHC(ll)l77>. 

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