Case fused strategy

More recently, a catalyst-free aqueous version of this strategy was proposed with simple acyclic 1,3-dicarbonyls, formaldehyde, and styrene or anilines derivatives (Scheme 40) [131], In the first case (Scheme 40), the very reactive 2-methylene-1,3-dicarbonyl intermediate reacts smoothly at 80°C with a variety of substituted styrenes to give the corresponding dihydropyrans in moderate to good yields. Remarkably, when styrenes were replaced by A-ethylaniline, a novel five-component reaction involving twofold excess of both formaldehyde and 1,3-dicarbonyl selectively occurred (Scheme 41). The result is the formation of complex fused pyranoquinolines following a Friedel-Craft alkylation - dehydration sequence to furnish the quinoline nucleus, which suffers the Hetero-Diels-Alder cyclization in synthetically useful yields. 

Very much the same strategy is used to synthesize a quinolone that contains an additional fused ring. This agent features a broad-spectrum antibacterial activity in spite of the lack of a nitrogen substituent at position 7. It is of note in this case... 

There are not many examples of syntheses of fused 1,3,5-triazines from [5 +1] atom cyclizations. The basic synthetic strategy is similar to the syntheses of 1,3,5-triazines from biguanides, but in this case the five-atom component incorporates a heterocyclic substituent. The examples in equations (55)—(57) illustrate the approach (74JHC991,75HCA761,80JHC1121). 

The preparation of fused nitrogen heterocycles such as pyrrolizidines, indolizidines, quinolizidines, pyrrolidinoazocines and piperidinoazocines by the RCM of appropriate dienes (equation 38), is another case where presence of a ring assists the RCM reaction. However, when n = 7 (with x = 1), the C=C bonds, separated by 11 single bonds, are too far apart for RCM to occur. Applications of this general strategy are in prospect for the formation of fused nitrogen heterocyclic systems in problems of alkaloid synthesis240. 

The potential of sequential radical addition as a powerful method to achieve the formation of five-membered rings was fully realized in the tandem radical cyclization strategy devised by Curran for the synthesis of triquinanes. In the case of linearly fused triquinanes, such as hirsutene 90 (Scheme 3.40), this strategy implies the retrosynthetic disconnection of the tricyclic framework by the application of two sequential radical cyclization transforms at rings A and... 

In the case of quadrone (Section 3.2.5), one is pretty much stuck with the complex construction of the fused rings of A, B, and C and elaboration of an applicable strategy centered around this core. On the other hand, the lactone ring D is easy to formulate at the latter stages and therefore the presence of this moiety has no strategic ramifications. 

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