Stereochemistry polycyclic systems

The early Escherunoser-Stork results indicated, that stereoselective cyclizations may be achieved, if monocyclic olefins with 1,5-polyene side chains are used as substrates in acid treatment. This assumption has now been justified by many syntheses of polycyclic systems. A typical example synthesis is given with the last reaction. The cyclization of a trideca-3,7-dien-11-ynyl cyclopentenol leads in 70% yield to a 17-acetyl A-norsteroid with correct stereochemistry at all ring junctions. Ozonolysis of ring A and aldol condensation gave dl-progesterone (M.B. Gravestock, 1978 see p. 279f.). 

Gratifyingly, when compound 24 is refluxed in a solution of toluene at 110°C, it undergoes quantitative [4+2] cycloaddition to polycyclic system 25. The indicated stereochemistry of 25 was anticipated on the basis of the trans,trans geometry of the phenyl-diene system in precursor 24 and the presumed preference for an exo transition state geometry. These assumptions were vindicated by the eventual conversion of 25 to endiandric acids A (1) and B (2). 

The predictable stereochemistry of the ring closure of substituted 5-hexenyllithiums, coupled with the ease with which the product organolithium may be functionalized, permits rational design of synthetic routes to polycyclic systems by sequential anionic cyclizations of polyolefinic alkyllithiums.12 The preparation of stereoisomerically pure e do-2-substituted bicyclo[2.2.1]heptanes is illustrative of this approach to polycyclic systems.12... 

It is worth noting that in this synthesis of Cecropia juvenile hormone a strategy which is the reverse of the one developed by W.S. Johnson [8] for the synthesis of steroids and other fused polycyclic systems bearing cyclohexane rings is used. This method involves a non-enzymatic cyclisation of a polyunsaturated intermediate with the appropriate stereochemistry (all-trans) (Scheme 13.3.6). Such cyclisation occurs with a really amazing stereoselectivity and several new chiral centres with the correct stereochemistry are created in one single step ... 

The third example of chirality without a chiral centre is provided by spiro compounds, which we shall meet later when we consider the stereochemistry of polycyclic systems (see Section 3.5.1), but at this stage it is worth noting that they provide a third example of chirality... 

Because of the cumbersome and usually exasperating nature of the von Baeyer system of formal nomenclature,422 especially when applied to complex polycyclic systems, a colloquial nomenclature has been developed for the higher poly-quinanes.415,42 The system applies only to polycondensed, fused, equal-size ringed molecules (no spiro fusions) and states the total number of carbon atoms, the number of basic rings, and their size. An indicator of ring juncture stereochemistry is also required on occasion, a symmetry designation must be added. Thus, all-cis-484 is (Q-C 14-tetraquinane and all-cis-485 is(C2)-Ci4-tetraquinane. 

Bromine and iodine were both effective for the cyclization of l-aza-4-cyclooctene to the corresponding pyrrolizidine 3 which is obtained in good yield without conflicting amine oxidation. The cyclization of l-aza-5-cyclonene and of cyclophenylalkanamines was similarly performed (Table 6) 3-121 23>, The total stereoselectivity is dependent on either the strain connected with the polycyclic system or the tram addition to the double bond. The stereochemistry of the products was confirmed by X-ray analysis. 

The intramolecular variant of the hetero-Diels-Alder cycloaddition is attractive since it allows the stereochemistry of the products to be controlled at four centers or even more, if substituents in the bridging chain are considered. Following the experimental procedures devised for inter-molecular cycloaddition, a number of bicyclic and polycyclic systems have been prepared with the... 

Cocyclotrimerization, if applied to 1,5-hexadiynes 7, leads to benzocyclobutenes 8. After smooth thermal ring opening, these give highly reactive ort/io-quinodimethanes 9, which can be trapped by Diels-Alder reaction with an alkene or hetero-carbon multiple bond. If these dienophiles are in a side chain of the primary diync, the conversion leads in a one-pot version to carbo- and heterocyclic polycyclic systems with defined trans stereochemistry at the newly... 

Corey s analysis to) of polycyclic systems and strategic bond disconnections directed by maximizing simplification of intermediates is an example of the definition of new heuristics for skeletal dissection ( 6). This analysis directs the selection of particular bonds for construction. His rules also derive in part from stereochemical considerations ( 7). A further treatment of rules for bond selection via stereochemistry would be valuable. 

In the investigation of the total synthesis of steroids, not only have new chemical reactions been discovered and ones known earlier modified, but extremely delicate methods for the selective performance of chemical transformations have been developed. Moreover, with the results obtained in total steroid synthesis, the stereochemistry of condensed polycyclic systems has been given a new impetus and further development. 

Stereochemistry of Polycyclic Systems. Two aspects of the stereochemistry of polycyclic compounds are of the greatest interest for the total synthesis of steroids, namely the comparative stability of the spatial isomers of these compounds and the influence on them of double carbon-carbon bonds in various positions of the cyclic system. 

Schleyer PVR. Torsional effects in polycyclic systems. II. The stereochemistry of attack and departure in norhomane derivatives. J. Am. Chem. Soc. 1967 89 701-703. 

Intramolecular cyclizations offer a versatile method for the preparation of bicyclic and polycyclic ketones. Indeed, in favorable cases, reaction can ensue on simply heating the acyl halide " as well as on treatment with a Lewis acid, offering control of the product isolated (Scheme 3). However, the structural constraints imposed in detailed examination of specific ring systems in which the stereochemistry of cyclization can be determined may well preclude the deduction of more general conclusions about stereochemical control. 

Using these techniques (combinatorial biosynthesis) with streptomycetes, the polyketides have now been investigated, including not only the macrolides (e. g., erythromycin) but also polycyclic aromatic compounds (e.g., actinorhodin, tetracenomycins). The formation of hybrids can alter not only the size of the poly ketide skeleton, its stereochemistry or its functionality but also enzyme systems of the later steps of biosynthesis such as, e. g., oxygenases or glycosy Itrans-ferases. In practice major difficulties arise because each intermediate in the biosynthetic sequence is a substrate for the following enzyme thus if a changed substrate is not accepted by the respective enzyme the biosynthesis breaks down. 

The ring closure of cyclic 2-but-3-enylcycloalkyl radicals (Fig. 7.3) is similar to that of the open-chain system, except that the constraints of the ring impose an almost exclusive 1,2-cis stereochemistry [3, 4]. The critical 1,5-selectivity is still largely cis, and it is this selectivity that has found the most use in the synthesis of polycyclic natural products [5, 6]. In the context of the 2-but-3-enylcyclopentyl radical cyclization, it was argued [7] that the l,5-c stereochemistry is favored because the chair-like transition structure 8a (Fig. 7.4) can achieve effective overlap between the SOMO and the radical center and the olefin n orbitals, with less strain than the other possible chair Sb. 

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