Stereochemistry ring compounds

Reactions of 1 with epoxides involve some cycloaddition products, and thus will be treated here. Such reactions are quite complicated and have been studied in some depth.84,92 With cyclohexene oxide, 1 yields the disilaoxirane 48, cyclohexene, and the silyl enol ether 56 (Eq. 29). With ( )- and (Z)-stilbene oxides (Eq. 30) the products include 48, ( > and (Z)-stilbenes, the E- and Z-isomers of silyl enol ether 57, and only one (trans) stereoisomer of the five-membered ring compound 58. The products have been rationalized in terms of the mechanism detailed in Scheme 14, involving a ring-opened zwitterionic intermediate, allowing for carbon-carbon bond rotation and the observed stereochemistry. 

Nuclear Overhauser enhancement spectroscopy (NOESY) experiments play a very important role in structural studies in quinolizidine derivatives. For instance, the endo-type structure of compound 28 was proven by the steric proximity of the H-3a and H-12a protons according to the NOESY cross peak, while the spatial proximity of the H-6f3 and H-8/3 protons reveals that tha A/B ring junction has a /ra t-stereochemistry. Similarly, compound 28 could be distinguished from its regioisomer 29 on the basis of the NOESY behavior of its H-13 atom <1999JST153>. 

Addition of lithiated heterocycles to aldonolactones yields carbon-linked nucleosides (56). Thus, the reaction of 2,3 5,6-di-O-isopropylidene-L-gu-lono-1,4-lactone (9b) or 2,3-O-isopropylidene-D-ribono-l,4-lactone (16a) with various lithiated heterocycles gave gulofuranosyl derivatives 53a-g or ribofuranosyl derivatives 54b,c. Gulonolactols 53a-g and ribonolactols 54b,c were acetylated with acetic anhydride in pyridine to yield their acetyl derivatives. The stereochemistry of compounds 53a-g and 54b,c was discussed in terms of the Cotton effect of circular-dichroism curves of the ring-opened alcohols formed upon reduction by sodium borohydride. The configuration at C-l of 53g was proved by means of X-ray analysis (57,58). 

The formation of heterocycles by cycloaddition reactions of conjugated dienes is the subject of this chapter. Almost the entire account is devoted to the Diels-Alder reaction of dienes with heterodienophiles to yield six-membered ring compounds (equation 1). Many such reactions have been reported and there is a plethora of reviews. Somela p are general others are cited at appropriate places in the text. This account is highly selective, concentrating on recent work with particular regard to the stereochemistry of these processes. 

Carbocyclic molecules occupy a special position in stereochemistry. While Barton s proposal (80) triggered explosive developments in the conformational analysis of six-membered ring compounds (80a), the inability of the qualitative theory to interpret the behavior of rings other than six membered prompted Hendrickson to utilize the MM method (9b). Further developments in this area have been well summarized (10, 81). Some of the more recent topics are mentioned below. 

We have discussed in this chapter the thermal pyrolyses of a number of strained ring compounds. In most of the cases considered there is good evidence that the processes are unimolecular. Where possible we have tried to suggest plausible transition complexes, and reaction paths, based on a consideration of such factors as the kinetic parameters, stereochemistry of the reaction and effect of substituents. In reactions of this type, the description of the transition complex is fraught with difficulties, since the absence of such things as solvent effects (which can be so helpfrd in bimolecular reactions) limit the criteria on which such descriptions may be based. Often two types of transition complex may be equally good at accounting for the observed data. Sometimes one complex will explain some of the data while another is better able to account for the remainder. It is probable that in many cases our representation... 

Other X-ray analyses (78JOC3513) together with H and 13C NMR spectroscopic data have given a firm basis for the stereochemistry of this class of ring compounds. The information has helped to clarify steric problems of other phosphorus heterocycles, e.g. (117)-(120), where the difficulties of interpretation of NMR or other physical data are greater. 

Hirsutine (85) is a corynantheine-type indole alkaloid with a C/D cis ring juncture (pseudo stereochemistry). This compound has recently been found to exhibit highly potent inhibition of the replication of the strains of influenza A (subtype H3N2) [63]. The EC50 of hirsutine was 11- to 20-fold more potent than that of the clinically used ribavirin. Exploration of the important structural features of this molecule revealed that the stereochemistry at C-3 (.R) and C-20 (R) as well as the presence of the Nb lone pair were essential for the anti-influenza A activity. Thus, the C-3 epimer, dihydrocorynantheine (86) (normal stereochemistry), was much less active than hirsutine (85). 

In the system DARC [228], a special input device (called topocodeur) is used. In computer-assisted organic synthesis, the most widely used input/output method is by means of VDUs [229—232]. This type of input/output is the most familiar to a chemist, since molecules are drawn on the VDU in their usual shape. It is especially interesting for ring compounds and allows us also to deal with the stereochemistry by means of the usual symbols. Although the input via a VDU requires sophisticated hardware, it will probably be used more and more. 

More recently, Usuki etal. studied, using NMR techniques, the conformation of spirocyclic oxaziridines 3 derived from substituted cyclohexanones <1995JOC8028>. Depending on substitution and on the stereochemistry, these compounds exhibit a substantial upfield shift of the cyclohexyl methylene or methane protons with a 1,3-diaxial relationship to the oxaziridine N-substituent. This effect is ascribed to a conformation that places an aromatic group over the plane of the cyclohexane ring. This conformation has also been observed in the solid state by X-ray crystallography and is further supported by molecular mechanics calculations. 

Ohloff G. Relationship between odor sensation and stereochemistry of decalin ring compounds. In Gustation and Olfaction. 1971. Ohloff G, Thomas AF, eds. Academic Press, London, pp. I78-I83. Bersuker IB,DimogIo AS, Gorbachov MY, Koltsa M, Vlad PE. New J. Chem. I985 9 2II. 

The Diels-Alder reaction is a key reaction in organic synthesis. Its high versatility in the synthesis of six-membered ring compounds and its potential for the control of up to four stereogenic centers have attracted much attention. Lewis acid catalysis has further enhanced the scope of this reaction. Lewis acids activate the dienophile by coordination to a Lewis basic substituent (usually a carbonyl group) and direct the stereochemistry. Boron Lewis acids are often the catalysts of choice for the Diels-Alder reaction. Early (Ti(IV)) and late (Cu(II)) transition metal complexes in combination with chiral ligands have also been used with much success and the reader is referred to the relevant chapters in this book. 

Here we consider 1,3-dimethylcyclohexane (15) and assign its stereochemistry. This compound has another chair conformation 16, derived from 15 by ring inversion, and we now assign configuration from both conformers. 

---