Ring systems annulation

Heterocyclic ring systems annulated to cyclopentyl radicals can be considered as two simultaneously present substituents, cis-Annulated ring systems in the /i.y-position to the radical center are found to give tram selectivities which are larger than when a single -substituent is present. Bicyclic radicals with an overall bend shape are often exclusively attacked by alkenes from the convex face. 

When the radical center is located at the ring junction of a ring system annulated to a cyclopentyl radical, the annulated ring serves as an a-, as well as a f)-, or y-substituent. This is the case in furanose radicals, in which the isopropylidene group serves as a second cyclopentyl ring22. The attack of dodecanethiol as hydrogen donor occurs in such a way that the cis ring system is formed exclusively. 

Sulfimides have been utilized extensively for the synthesis of monocyclic ring systems as well as ring annulations. 

The only known example under such heading is that incorporating four nitrogen atoms, the tetrazoloquinoline. Although they can exist in two annulated ring systems, only examples of one of them, l,2,3,4-tetrazolo[l,5-ajquinolines are reported (Fig. 11). 

In contrast to the IJK system 86, compound 87 (Scheme 17a) poses a much steeper synthetic challenge it is during the course of the synthesis of 87 that the diabolical bis(oxepane) problem would have to be dealt with. At this phase of the project, we had benefited from a good deal of experience with the bis(oxepane) problem, and this experience provided the foundation for a conservative solution. Starting from FG ring system 105, it was hoped that rings E, D, C, B, and A could be annulated sequentially and in that order (Scheme 17c). 

This ring system could be prepared by building either of the two heterocycles and then doing an annulation. Thus, cyclization of ethyl o-nitrophenylhydrazonocyanoacetyl carbamate 552 afforded 553. Reduction of 553 by the action of iron(II) sulfate gave 554, which on acid hydrolysis gave 558. Cyclization of o-aminophenyl derivatives 554 and 558 to 555 and 559, respectively, was effected (77CCC894) by treatment with acid. Phthalimido derivatives of 554 could also be cyclized to this... 

For 10 years, attention has been focused on the intramolecular additions ofallylic and alkynyl-silanes to enones. In early studies, a variety of Lewis acids were tested and reaction conditions were optimized to make this reaction a powerful tool in the synthesis of spiro-annulated, and 1,2-fused ring systems, which can be utilized in the total synthesis of natural products34,35. 

The selectivity for two-alkyne annulation can be increased by involving an intramolecular tethering of the carbene complex to both alkynes. This was accomplished by the synthesis of aryl-diynecarbene complexes 115 and 116 from the triynylcarbene complexes 113 and 114, respectively, and Danishefsky s diene in a Diels-Alder reaction [70a]. The diene adds chemoselectively to the triple bond next to the electrophilic carbene carbon. The thermally induced two-alkyne annulation of the complexes 115 and 116 was performed in benzene and yielded the steroid ring systems 117 and 118 (Scheme 51). This tandem Diels-Alder/two-alkyne annulation, which could also be applied in a one-pot procedure, offers new strategies for steroid synthesis in the class O—>ABCD. 

Recently we have been able to produce coumarins by alkyne annulation in the presence of CO (Scheme 13).14 Production of the coumarin ring system is... 

In another approach, the annulated [5.6.5] ring system 3-259 was obtained from 3-258 in a radical reaction in 61 % yield (Scheme 3.67) [106]. This motif is found as the central core in several important natural products. 

Thiemann and coworkers [68] sought novel types of steroids with different biological activity, and in doing so prepared areno-annulated compounds such as 6/1-133 (Scheme 6/1.35). This is achieved with a Heck reaction of 6/1-132 with an acrylate, followed by an electrocydic ring closure of the formed hexatriene. The reaction is then terminated by removal of the nitro group, with formation of the aromatic ring system. 

Although 1,3,2-diazaphospholenium cations are usually prepared from neutral NHPs or 1,3,2-diazaphospholes via Lewis-acid induced substituent abstraction or A-alkylation, respectively (cf. Sect. 3.1.2), the group of Cowley was the first to describe a direct conversion of a-diimines into cationic heterocycles by means of a reaction that can be described as capture of a P(I) cation by diazabutadiene via [4+1] cycloaddition [31] (Scheme 4). The P(I) moiety is either generated by reduction of phosphorus trihalides with tin dichloride in the presence of the diimine [31] or, even more simply, by spontaneous disproportionation of phosphorus triiodide in the presence of the diimine [32], The reaction is of particular value as it provides a straightforward access to annulated heterocyclic ring systems. Thus, the tricyclic structure of 11 is readily assembled by addition of a P(I) moiety to an acenaphthene-diimine [31], and the pyrido-annulated cationic NHP 12 is generated by action of appropriate... 

Several interesting 1,2,4-triazole fused-ring systems have been reported. A facile synthesis of 3,5-dihydro-677-imidazo[l,2-fc]-l,2,4-triazol-6-ones 162 was obtained by an iminophosphorane-mediated annulation <06EJ04170>. 8-Trifluoromethyl-l,2,4-triazolo[4,3- >]pyridazines 163 has been prepared from 4-trifluoromethyl-4,5-dihydropyridazin-3-one... 

The above examples represent Jl-heteroaromatic annulation involving the reaction of allyl anions whose double bond is a part of the heterocyclic ring system (Scheme 1). The corresponding a-oxoketene dithioacetals (1,3-electrophilic component) were generally derived from nonheterocyclic carbonyl precursors. Alternatively the Jl-heteroaromatic annulation can also be employed to a-oxoketene dithioacetals derived from heterocyclic ketones (1,3-bielectrophile) and hetero/nonheteroallyl anions (1,3-binucleophile). These reactions are described below. 

A number of other ring systems have been prepared by intramolecular bis-annulation procedures. Pyrrolothiadiazolines 174 were prepared by condensation between hydrazides and compound 173 (Equation 14) <1998JPR676>. The thermally induced intra-intermolecular criss-cross cycloaddition of azine 175 in the presence of phenyl isocyanate leads to heterocyclic compound 176 containing three fused five-membered rings (Equation 15) <2002TL6431>. 

Strategies based on two consecutive specific reactions or the so-called "tandem methodologies" very useful for the synthesis of polycyclic compounds. Classical examples of such a strategy are the "Robinson annulation" which involves the "tandem Michael/aldol condensation" [32] and the "tandem cyclobutene electrocyclic opening/Diels-Alder addition" [33] so useful in the synthesis of steroids. To cite a few new methodologies developed more recently we may refer to the stereoselective "tandem Mannich/Michael reaction" for the synthesis of piperidine alkaloids [34], the "tandem cycloaddition/radical cyclisation" [35] which allows a quick assembly of a variety of ring systems in a completely intramolecular manner or the "tandem anionic cyclisation approach" of polycarbocyclic compounds [36]. 

In the first method, a dialkylzinc reagent bearing an acetal moiety at the d-posi-tion is used (Scheme 7.25(b)). The catalytic 1,4-addition is followed by acetal hydrolysis and aldol cyclization of the 4-substituted cycloalkanone, affording 6,6- (92), 6,7-, (93) and 6,8- (94) annulated ring systems with high enantioselectivities (>96% ees) [80]. In addition, dimethyl-substituted decalone 95, with a structure frequently found in natural products, is readily obtained in enantiomerically pure form. 

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