Conformations of the Six-Membered Rings

FIGURE 2.24 Variants of the six-membered ring conformations chair (C), half-chair H), skew (5), boat (B), and envelope ( ). 

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Amides 1-4 all adopt conformations in wiiich a i-butyl group has an axial-like position and, as a result, a non-chair conformation of the six-membered ring. Comment on the origin of this stmctural effect. 

NOE and NOESY experiments have established the stereochemistry of lactams 34a and b (01TL6995) and of thioethers 368a and b (see Scheme 84) (07T8267), respectively. The X-ray structure analysis of allene 77a shows a half-chair conformation of the six-membered ring (92T2081). 

The chair conformation of the six-membered ring in such compounds can be stabilized by hydrogen bonding by incorporation of an additional hydroxyl group, for example, compound 6 <2005JOC7107>. 

Apaydin et al. (97JMS(T)113) also calculated the conformational equilibria of some 5-substituted 1,3-dithianes by the PM3 method in the gas phase and in solution, displaying a resonable agreement with available experimental data. The chair conformation of the six-membered ring was confirmed the equatorial position of the substituents in position 5 (alkyl, OMe, SMe) are the most stable in all media and the effect of the solvent on the equilibrium is only minor. 

The conformations of the six-membered ring systems are better characterized than those of the less stable five-membered analogues. For example, the cyclohexane molecule can occur in two strainless forms, namely in the rigid chair form or in the flexible form (Fig. 2-9). The latter can exist in a variety of shapes of which only the boat and the skew boat (or twist) are regular and easily depictable on paper. The chair form is preferred energetically because it is usually free from steric interactions whereas the flexible forms are not. The half-chair conformation is possible, when a six-membered ring contains either a double bond or an oxiran ring. In the half-chair conformation four adjacent atoms are in the same plane. 

Rules of the Fischer Projection Mutarotation The Haworth Projection The Mills Projection The Reeves Projection Conformations of the Six-Membered Rings Conformations of the Five-Membered Rings Conformations of the Seven-Membered Rings Conformations of Fused Rings Steric Factors... 

These trends are explained by analysis of the structures of the reactive conformations of the enones and the structures of die cyclopentenylic cations. Considering the 7-substituted series (18) the reactive half-chair conformation (23) places the substituent in an equatorial position (Scheme 21). In the cations resulting from conrotation (24 and 25) all atoms in the five-membeied ring must lie in a plane, thus precluding an equatorial hydrogen. Thus the two conrotations, clockwise to (24) and counterclockwise to (25), lead dir y to chair or boat conformations of the six-membered rings, respectively. The size of the substituent then plays two roles first to fix the ring ccmformation and second to enha opposite face tqiproach. 

Fig. 24 shows as an example the construction of the bicyclo[3.2.1]octane skeleton, which consists of one five-membered and one six-membered ring system (SSSR). In the first step, the two low-energy conformations, the envelope conformation of the five-membered and the chair conformation of the six-membered ring, are combined. Also, the more strained boat conformation of the six-membered ring can be fused to the envelope form of five-membered ring. 

This type of six-membered ring system with four heteroatoms does not occur in nature. Scarce spectroscopic data are available. The molecular structures of a 3,6-diaryl-l, 4,2,5-dithiadiazine1 and a 6-aryl-l,4,2,5-dithiadiazin-3-amine were examined.5 The crystal structure of 3,6-bis(4-methoxyphenyl)-l,4,2,5-dithiadiazine shows a boat conformation of the six-membered ring system.3 The structure was also determined by crystallographic analysis of 6-(4-chlorophenyl)-3-morpholino-l,4,2,5-dithiadiazine.5 Some theoretical studies on the thermal decomposition reactions of dithiadiazines have been performed.9... 

Since tropine esters show smaller rates than -tropeines and since boat conformations of the six-membered ring are postulated, these facts were attributed to the hydroxyl group hindered in the former case by a neighboring N-CH3 group. Thus configurations opposite to those established by chemical means have been ascribed to the epimers. These views have been revised and corrected by the same workers (10). 

The reactivity of six-membered systems is problematical, since ring strain is no longer a dominant feature. A complex balance of forces may pertain in addition to those considered by Westheimer s guidelines. Steric, stereoelectronic, electrostatic, solvation and other effects may dominate the dynamics of six-membered TBP intermediates. However, it is probable that the conformation of the six-membered ring itself plays a major role in determining the balance of these effects and hence reactivity. 

Photoelectron spectroscopic data, marked (PE) , are from Ref. [20, 25]. The numbers in boldface type are from X-ray crystallography [12, 26]. For discussion of the conformations of the six-membered ring hydrazines, see Ref. [27]. Entries in parentheses are for data taken on very close structural analogues to compounds that have experimental data, for which we believe the 9 values given also apply. 

The most stable conformation of the six-membered ring is the twist form, in agreement with the experimental result. It is more stable by 3.7 kcal mor than the five-membered ring (Fig. 7). A comparison of the calculated geometry with the X-ray structure data shows good agreement... 

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