Cyclic compounds, stereochemistry

Electrocyclic reactions of 1,3,5-trienes lead to 1,3-cyclohexadienes. These ring closures also exhibit a high degree of stereospecificity. The ring closure is normally the favored reaction in this case, because the cyclic compound, which has six a bonds and two IT bonds, is thermodynamically more stable than the triene, which has five a and three ir bonds. The stereospecificity is illustrated with octatrienes 3 and 4. ,Z, -2,4,6-Octatriene (3) cyclizes only to cw-5,6-dimethyl-l,3-cyclohexadiene, whereas the , Z,Z-2,4,6-octa-triene (4) leads exclusively to the trans cyclohexadiene isomer. A point of particular importance regarding the stereochemistry of this reaction is that the groups at the termini of the triene system rotate in the opposite sense during the cyclization process. This mode... 

Consecutive Michael additions and alkylations can also be used for the diastereoselective synthesis of 5- and 6-membered ring systems. For instance when 6-iodo-2-hexenoates or 7-iodo-2-heptenoates are employed the enolate of the Michael adduct is stereoselectively quenched in situ to provide the cyclic compound with trans stereochemistry (>94 6 diastereomeric ratio). As the enolate geometry of the Michael donor can be controlled, high stereoselectivity can also be reached towards either the syn or anti configuration at the exocyclic... 

The stereochemistry of Ireland-Claisen rearrangements of cyclic compounds is sometimes indicative of reaction through a boat TS. For example, the major product from 2-cyclohexenyl propanoate is formed through a boat TS.244... 

Since most SH2 displacements occur at univalent atoms, tests of stereochemistry at the reaction center are ordinarily not possible. Substitutions do nevertheless occur at saturated carbons in highly strained rings.131 Halogen atoms attack cyclopropane (Equation 9.76) and other strained cyclic compounds,... 

Chapter 2 focuses on conformational analysis as a tool for assessing the relative reactivity and stereochemistry of cyclic compounds. 

The 191 problems in this book cover most of the area of stereochemistry, including nomenclature, stereogenic elements (centers, axes, planes) and their descriptors, symmetry, inorganic stereochemistry, determination of enantiomer excess, conformation of acyclic and cyclic compounds, and more. The answers, in addition to providing solutions to the problems, frequently include additional explanations of the underlying principles. The problems are ordered more or less in order of increasing difficulty. (I had a hard time with some of the problems toward the end myself )... 

Several indium-mediated intramolecular carbonyl allylation reactions have been investigated, and it has been found that these reactions provide an easy access to a variety of cyclic compounds. The intramolecular cyclization of 49a-c mediated by indium in aqueous media proceeds smoothly to afford carbocyclic systems containing y-hydroxy-Q -methylene esters 50a-c, which either spontaneously or readily cyclize to give fused o -methylene-y-butyrolactones 51a-c (Scheme 52). The same cyclization of 49d is too slow to compete with the side-reaction, in which the bromide is substituted by a hydroxy group. The ring junction stereochemistry of fused lactones 51 has been found to be cis in all cases. Of the two possible transition states, the one leading to the m-fused compounds is preferred, because the chair-chair conformation is favored over the chair-boat conformation.209... 

This chapter is about rings and stereochemistry. Stereochemistry is easier to understand in cyclic compounds and that alone might make a separate chapter worthwhile. But there is something much more fundamental behind this chapter. Stereochemistry is better behaved in cyclic compounds. Suppose you were to reduce this ketone to one of the corresponding alcohols. 

Another problem from the chapter, The synthesis of the starting material for this reaction is a good example of how cyclic compounds can be used in a simple way to control stereochemistry. Draw mechanisms for each reaction and explain the stereochemistry. 

How could this cyclic compound be used to produce the open-chain compound with correct relative stereochemistry ... 

One important nitrone is a cyclic compound that has the structure below and adds to dipolarophiles (essentially any alkene ) to give two five-membered rings fused together. The stereochemistry comes from the best approach with the least steric hindrance, as shown. There is no endo rule in these cycloadditions as there is no conjugating group to interact across space at the back of the dipole or dipolarophile. The product shown here is the more stable exo product. 

The Syntex chemists reasoned that, if this methyl ketone could be made stereospecifically by fragmenting a cyclic starting material, the (hard-to-control) double bond stereochemistry would derive directly from the (easier-to-control) relative stereochemistry of the cyclic compound. The starting material they chose was a 5/6-fused system, which fragments to give one of the double bonds. 

Conformations of Three to Eive Memmbered Rings Stereochemistry of Cyclic Compounds... 

Several new thiophosphates (140) have been prepared. They are useful precursors of novel cyclic compounds (141) which have similar structures to Baylis-Hillman adducts. The synthetic approach to these compounds involves reduction of the carbonyl group by NaBH4 in the presence of methyl iodide which exhibit full axial selectivity. Subsequent oxidation of intermediate sulphides (142) to sulphoxides (143) and cis elimination of the latter affords the desired compounds (141) of defined stereochemistry (Scheme 42). Multifunctionality of the compounds makes them attractive for numerous further important transformations. ... 

Stereochemistry of the substitution on chiral carbon centers has been reviewed [15]. Cyclic compounds were taken as substrates to determine the stereochemical outcome, which was deduced to be an flnf/-fashion irrespective of the S 2- and SN2 -type reactions [Eqs. (48) 90 (49) 102 (50) 102 and (51) 115]. 

The stereochemistry of Hofmann elimination is commonly anti but less so than was formerly believed. Syn elimination is important for certain cyclic compounds, and can be made important even for open-chain compounds by the proper choice of base and solvent. Quaternary ammonium ions are more prone to syn elimination than alkyl halides and sulfonates. Electronically, anti formation of the double bond is favored in eliminations but when the alkene character of the transition state is slight—as here—other factors come into play conformational factors, it has been postulated. 

Cyclic compounds have fewer degrees of freedom than their acyclic counterparts and this means that not only can we expect a higher level of control, but the resulting stereochemistry is easier to visualise. So reduction of the achiral ketone 80 could lead to the syn alcohol 81 or the anti alcohol 82. The question is which do we get and why ... 

---