Conformational isomers cyclopropane

Cyclopropane (Fig.J) is a flat molecule in respect of C-atoms, with the hydrogen atoms situated above and below the plane of the ring, so it has no conformational isomers. Cyclobutane can form three distinct shapes-a planar shape and two butterfly shapes (fig.K). Cyclopentane can also form a number of shapes or conformations. The planar structures for cyclobutane and cyclopentane are too strained to exist in practice because of eclipsed C-H bonds. 

From the entropies of disordering in Fig. 5.141, one notes that cyclododecane gains almost no disorder in the low-temperature transition, while cyclotetraeicosane may develop 11 to 18 conformational isomers [calculated from 127.7/(7 to 12), based on Fig. 2.103]. The conclusion reached is that cyclododecane may undergo rotoreptation, a rotation with simultaneous change of conformational isomers. This motion leads to little disorder, particularly in a jump-hke motion. Schematically, this jump process is shown in Fig. 5.142 for cyclodoeicosane. One can treat this rotoreptation similat to the jump-rotation, seen in cyclopropane and benzene [46]. 

The same stereochemical principles apply to both acyclic and cyclic compounds. With simple cyclic compounds that have little or no conformational mobility, it can even be easier to foUow what is going on. Let us first look at cyclopropane-1,2-dicarboxylic acid. These compounds were considered in Section 3.4.3 as examples of geometric isomers, and cis and trans isomers were recognized. 

Artemisyl, Santolinyl, Lavandulyl, and Chrysanthemyl Derivatives.— The presence of (41) in lavender oil has been reported earlier. Poulter has published the full details of his work (Vol. 5, p. 14) on synthetic and stereochemical aspects of chrysanthemyl ester and alkoxypyridinium salt solvolyses (Vol. 3, pp. 20—22) and discussed its biosynthetic implications. Over 98% of the solvolysis products are now reported to be artemisyl derivatives which are formed from the primary cyclopropylcarbinyl ion (93) which results from predominant (86%) ionization of the antiperiplanar conformation of (21)-)V-methyl-4-pyridinium iodide the tail-to-tail product (96 0.01%) may then result from the suprafacial migration of the cyclopropane ring bond as shown stereochemically in Scheme 3. This is consistent with earlier work (Vol. 7, p. 20, ref, 214) reporting the efficient rearrangement of the cyclobutyl cation (94) to (96) and its allylic isomer, via the tertiary cyclopropylcarbinyl cation (95). ... 

Davies and co-workers have explored the role of ligand conformation in the ruthenium(II)-catalyzed cyclopropanation of styrene.10 This study was based on results reported by Nishiyama in which the catalyst prepared in situ from pyridine-bis(oxazoline) 62 and RuCI2(/>cymene) 2 was found to be highly active and selective in the reaction of ethyl diazoacetate with styrene (66% yield, 84% de, and 89% ee of major trans-isomer).52 Several ligands hindered on the oxazoline ring, including 3, were tested and poorer yields and selectivities were obtained (for 3, 50% yield, 81% de, and 59.5% ee of major trans-isomer), which indicated unfavorable steric interactions between styrene and the Ru(in-pybox) carbene complex (Scheme 17.22).10... 

It has been found that the reaction of dimethyloxosulfonium methylide and diazomethane with (E)-3-aryl-2-phosphonoacrylates (346) using the (-)-S-phenyl-menthyl group as a chiral auxiliary gives the trans cyclopropane derivatives with high diastereoselectivity. This can be attributed to the high Jt-face differentiation of the acrylate moiety by the face-to-face interaction with the phenyl ring of the chiral auxiliary in the s-cis conformer. On the other hand, (Z)-isomers of (346) gave a mixture of cis and trans cyclopropane derivatives with low diastereoselectivity (Scheme 93). ... 

The preparation of optically active cyclopropanecarboxamides 64 has been achieved starting from an organometallic chiral auxiliary. The (R)- and (5)-crotonoyliron complexes show good diastereoselectivity for the Z conformer when treated with diethylzinc, zinc(II) chloride and diiodomethane. A 10 1 mixture of (i ,i ,5// ,5,/ )-diastereomers was obtained. Starting from the (/i)-isomer, (-)-(/ )-62, decomplexation of the cyclopropanated intermediates (R,R,S)- and (R,S,R)-63 with bromine in the presence of (4-)-(7 )-l-phenylethylamine gave the corresponding cw-substituted amides 64 in a ratio of 10 1. 

Enantiocontrol in intramolecular cyclopropanation reactions of diazoacetamides has been developed to levels comparable with those now accessible with diazoesters. Several substituent variations in Eq. (20) are summarized in Table 3, which reveals examples where ee s exceed 90%. In general diazoamides have a conformational feature which differs from their diazoester counterparts, namely, the relatively slow syn-anti isomerization by rotation about the N-CO bond. If the interconversion of (18) and (19) or their respective metal carbenes is slow relative to the reaction timescale [50], only isomer (18) can lead to intramolecular cyclopropanation. However, an alternative process to which (18) is prone un-... 

The next example is of the Isomers for substituted cycloalkanes [77], assumed to undergo such rapid configurational changes as to average the environment of equatorial/awal substituents, so that only the avers e planar ring conformation need be considered [78]. We shall illustrate the enumeration with substituted cyclopropanes whose cycle indices can be obtained from the symmetries of the graphs S-7,... 

Disregarding the possibility of transfusion of the cyclopropane ring with the five- and the slx-membered ring reduces the number of stereoisomers of the toxlsterols C to four as represented In Figure 21. Inspection of molecular models shows that Isomer I Is without unfavorable sterlc features. In Isomer II there Is crowding of the methyl groups CH3-I8 and CH3-I9, whereas In Isomers III and IV ring C must have a boat conformation. 

The important conclusion drawn from this study (30) was that acetylcholine would most probably interact with muscarinic receptors in its less favored anticlinal conformation. The most active isomer, the (+)-f/ ans-enantiomer, of these cyclopropane analogues was found to have a torsion angle of 137° (anticlinal) between the ester oxygen and the quaternary nitrogen. This is significantly different from the 60° torsion angle in the synclinal conformation found by NMR and x-ray determinations to be the preferred conformation. 

The copper (I) catalyzed cyclopropanation of amino acid protected pyrroles 37 with methyl diazoacetate proceeds smoothly to afford exclusively the exo-isomers 38 and 39, which were utilized as precursors to conformationally restricted peptides having a aminocyclopropane carboxylic acid <97SL202>. 

The formation of spiro [4,2] hepta-1,4-dienes (97) and (98) by the reaction of dichloromethyl-lithium with 6-substituted fulvenes proceeds by a two-step process. Initial addition affords the cyclopentadienyl anion (96), which undergoes rapid 1,3-elimination, with a distinct preference for closure to the thermodynamically less stable cis-isomer (97) (Scheme 15). Only in the case of (96 R = Bu ) does the trans-cyclopropane (98) predominate. Such observations can be rationalized in terms of Eliel s predictions that a gauche conformation such as (96a) will be favoured over (96b) due to an attractive force between the halogen atom and the adjacent alkyl (or... 

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