Rigid polycyclic compounds

Centropolyindanes constitute a complete family of arylaliphatic polycyclic hydrocarbons containing several indane units. Mutual fusion of the five-membered rings leads to three-dimensional, carbon-rich molecular frameworks bearing a central carbon atom, such as benzo-annelated [3.3.3]propellanes, triquinacenes, and [5.5.5.6]- and [5.5.5.5]fenestranes. In this review, the structural concept of centropolyindanes is contrasted to other fused indane hydrocarbons. Besides the syntheses of the parent centropolyindanes and recently described related indane hydrocarbons, the preparation of a large variety of bridgehead and arene substituted centropolyindanes is presented including strained, heterocyclic, and centrohexacyclic derivatives. In appropriate cases, the particular reactivity and some structural features of these unusual, sterically rigid polycyclic compounds are pointed out. 

In the reaction of compounds 22, which have diene moieties embedded in rigid polycyclic frames, the carbonyl-face selectivity is completely reversed through protection of the carbonyl groups as mono- or fc-acetals. This suggests the use of protecting groups as stereodirectors (Sch. 10) [25],... 

The pentacoordinate organotin compounds 416a-c also contain a tridentate dianionic N,N,0-chelate ligand . The structure of 416c was determined by X-ray diffraction which conformed the rigid polycyclic structure proposed on the basis of H, B, C, and Sn NMR data in solution (S Sn —150.4 ppm) . In contrast, the dimethyltin compound 416a displays a fluxional structure in solution. 

AG <5 kcal/mole, AG 2 >10 kcal/mole). If the rate of reaction is fast with respect to conformational equilibration the relative populations of the conformers will be of major importance (Fig. 6b). This situation is often encountered with conformationally rigid systems (e.g., polycyclic compounds). Obviously, conformational control can also be brought about by increasing the rate of reaction. We have seen (Section 3) that some 1,2 shifts in carbocations are extremely fast (AG <5 kcal/mole). We expect, therefore, that rearrangements of carbocations may be competitive, at least, with conformational equilibration even in acyclic systems. 

Galanthamine is a natural alkaloid and a potent acetylcholinesterase inhibitor. Recognizing the potential to access this rigid polycyclic core through a biomimetic oxidative coupling/Michael addition, Shair and coworkers developed a highly efficient diversity-oriented synthesis based on this scaffold (Scheme 21.16) [96]. A library of 2527 compounds was prepared on the aforementioned macrobeads... 

The chemistry of centrotetraindane 8 has not been explored in detail. It may be noted, however, that the rigidity of the tribenzotriquinacene backbone renders the framework of 8 also conformationally rigid, giving rise to a single, Cs-symmetric conformer, as confirmed by X-ray structure analysis [114]. Bridgehead-functionalized derivatives of 8 should provide a wealth of further carbon-rich polycyclic compounds. 

Schreiber s early efforts in this area were focused on libraries of compounds having structural features reminiscent of rigid, complex, stereochemically rich natural products. In a key early example, solid-phase split-pool synthesis was used to generate a combinatorial library of over two million complex, polycyclic compounds derived from shikimic acid [17]. A stereoselective tandem acylation-nitrone cycloaddition was used to generate 18 tetracyclic scaffolds, to which 30 alkynes were coupled using a Sonogashira reaction, 62 amines were coupled via y -lactone aminolysis, and 62 carboxylic acids were coupled by alcohol esterification (Fig. 9.1-3(c)). In addition, a portion of the solid supports were left unreacted at each of the last three steps to generate a skip codon that further increased the diversity of the library. 

Syntheses of Polycyclic Systems.- Cram and co-workers have published a series of elegant syntheses of spherands- polycyclic compounds in which the rigid cavity is formed during their synthesis rather than in the course of complexation with cations. The preparation of (88) illustrates the strategy of their method. The binding units (89), (90), (91), (92) and (93) are assigned the... 

Notice that "stereoselectivity" means "order" and order means "negative entropy" which, in turn, means "rigidity", "lack of flexibility" or "absence of degrees of freedom". It is always easier to exert stereochemical control in rigid monocyclic or polycyclic systems than in the more flexible open-chain compounds (remember the limitations imposed by Corey s rule number 6 see 7.2.1). 

Therefore, a fundamental axiom in the synthesis of complex organic compounds bearing chiral centres is the necessity of resorting to rigid structures whether in the starting materials (monocyclic or polycyclic molecules) or in the transition states (as in pericyclic reactions, for instance) in order to ensure an... 

The first dataset consisted of 91 rigid compounds (mono- and di-substituted benzenes, polycyclic aromatic hydrocarbons, cyclic amides, and pyrazole and imidazole derivatives) selected from the WDI on the basis of a count of the number of rotatable bonds computed using TSAR none of the 91 structures had rotatable bonds. The structures are listed in Table 1 together with their experimental log Poct values, which cover a range from -2.17 to +6.5 the values were retrieved from the SRC web site (27). 

When a mineral or Lewis acid replaces the carboxylic component in the Passerini reaction, the final products are usually a-hydroxyamides. Also in this case, when chiral carbonyl compounds or isocyanides are employed, the asymmetric induction is, with very few exceptions, scarce [18, 19]. For example, the pyridinium trifluoroacetate-mediated reaction of racemic cyclic ketone 14 with t-butyl isocyanide is reported to afford a single isomer [19] (Scheme 1.7). This example, together with those reported in Schemes 1.3 and 1.4, suggests that high induction may be obtained only by using rigid cyclic or polycyclic substrates. 

The synthesis of enantiomerically pure compounds is the challenging problem for organic chemists. The synthesis becomes obsolete if the intermediates produce racemic mixtures. The problem is particularly acute when the asymmetric centers do not reside in a rigid cyclic or polycyclic framework. To be able to carry out efficient syntheses of complex molecules, chemists have to control the sense of chirality at each chiral center as it is introduced in the course of synthesis. Monoalkyl- or dialkyl-boranes exhibit a remarkable chemo-, stereo-, and regioselectivity for the hydroboration of unsaturated compounds. This property, coupled with the capability for asymmetric creation of chiral centers with chiral hydroboration agents, makes the reaction most valuable for asymmetric organic synthesis. In some of the cases, however, this has been achieved by diborane itself as shown in the synthesis of monensin by Kishi et al. A stereospecific synthesis of its seven carbon. component has been accomplished by two hydroboration reactions (Eq. 129) 209. ... 

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