Out-in isomers

Each macrocycHzahon could, in principle, lead to a mixture of diastereoisomers, depending on how the EtOOC residues at the two methano bridge C atoms are oriented with respect to each other (in-in, in-out, and out-out stereoisomerism) [92]. Usually, only out-out stereoisomerism has been observed so far. One exception is the in-out isomer 81. 

A) the in/out isomer 14 and the out/out isomer 15 were obtained, depending on which of the two possible niches of the first formed macrocycle is used for the intercalation of the monoamide. The third possible (in/in) isomer 16 could finally be formed when the substitution pattern was reversed (pathway B). The two pathways differ in the embedding compound, and interestingly for route B, where the nesting component bears the substituent, significant steric hindrance seems to accompany catenane formation - catenane 14 was obtained in only 2.7% yield, whereas route A leads to 17% of the same catenane. 

When macrocycle 65 is synthesized, the in/out isomer of [2]catenane 79 is also formed in 11% yield (Figure 29) [46]. A first attempt to methylate both sulfonamide groups by treatment of the DMF solution of 79 with iodomethane and potassium carbonate was successful. By bridging the two sulfonamide units with a bifunctional alkylating reagent, we were able to synthesize the first pretzel-shaped molecule [54]. Considerations of the X-ray structure analysis of amide-linked catenanes [16] and CPK models led to the diiodo compound 95 as a suitable brid-... 

Dodziuk, H., Nowinski, K.S. Topological isomerism should rotaxanes, endohedral fullerene complexes and in-out isomers of perhydrogenated fullerenes be considered as such Tetrahedron 54 (1998), 2917-2930. 

New catenane (cf. 17) and rotaxane (cf. 20) types have been obtained via supramolecular template syntheses The amide-based interlocked structures can be designed by appropriate choice of building units (cf. 13, 14) to form stable out/out, in/in and in/out isomers (cf. 17a, 17b), which can be separated [19]. It can be demonstrated that one of the two macromonocycles (cf. 15) of the... 

This route involves three successive cyclisations under high dilution conditions which limits the scale and yield of the overall synthesis severely. The parent macrotricyclic tertiary amines were obtained in 2-5 % overall yield and were quatemized under selected conditions giving the target structures 23-25 uncontaminated by in-out isomers. 

FIGURE 5.61 If the bridges are long enough, there is no angle strain in an in, out isomer. 

A special case of configurational isomerism is represented by the bicyclic host compounds 23 and 24. The synthesis yields both compounds in a 1 1 ratio (total yield 79%) 1. Since 23 and 24 are in/out isomers and can not be interconverted by conformational changes, a pair of ligands with different cavity size is obtained. The difference in size influences their binding abilities both molecules bind naphthalene as well as 2,6- and 2,7-dihydroxynaphthalene in aqueous solution, but only the more spacious out/out isomer 23 is able to complex adamantane and 1-adamantanethiol. To our knowledge this is the first complexation of a pure aliphatic hydrocarbon by any synthetic concave receptor. 

That the methyl group in the less substituted isomer of the enamine (20) is axial was borne out by the work of Johnson et al. (18) in the total synthesis of the glutarimide antibiotic //-dehydrocycloheximide (24). The acylation of the morpholine enamine of 2,4-dimethylcyclohexanone (25) with 3-glutarimidylacetylchloride (26), followed by the hydrolysis of the intermediate product (27) with an acid buffer, led to the desired product in 35 % yield. The formation of the product in a rather low yield could most probably be ascribed to the relatively low enamine-type aetivity exhibited by the tetrasubstituted isomer, which fails to undergo the acylation reaction, and also because in trisubstituted isomer one of the CHj groups is axial. Since the methyl groups in the product are trans to each other, the allylic methyl group in the less substituted isomer of the enamine should then be in the axial orientation. 

Cryptands of this type are able to exist in three isomeric forms since each of the bridgehead nitrogens may be orientated inwards or outwards with respect to the molecular cavity - the three isomers are thus in-in , in-out , and out-out . In the solid state, 2.2.2 has been shown to have an in-in arrangement (Metz, Moras Weiss, 1976). 

The diamines and their mono- and di-protonated ions can exist in various conformations, in which the nitrogen lone pairs and the protons on nitrogen are directed in (i or i+) or directed out (o or o+) from the molecular cavity. Diprotonated l,10-diazabicyclo[8.8.8]hexacosane, for example, may exist in either of the three forms in equation (79). When the out-out isomer of l,10-diazabicyclo[8.8.8]hexacosane bis hydrochloride (o+ o+) is dissolved in aqueous acidic solution, isomerisation to the in-in isomer (i+ i+) occurs so... 

Similar isomerizations of clopenthixol (354) and chlorprothixene (355) were observed but, unlike flupenthixol (353), the photostationary states of these mixtures differed significantly in their isomer ratios from those of the drugs as normally supplied. It was pointed out that the photoisomerizations could affect their potencies [195]. 

In contrast, isomers of 115 have so far not been isolated. An early attempt to generate cyclopropa[a,e]naphthalene (118) failed. More recently, the generation of dicyclopropa[a,c]naphthalene (119) was attempted by reaction of 120 with base. When the aromatization was carried out in the presence of DPIBF (44), stereoi-someric bis-adducts of cyclopropenes were isolated. However, the adducts provide no evidence for the formation of 119 as a reactive intermediate, since they are formed by sequential elimination-cycloaddition via 121. Cyclopropene interception of 121 is faster than further elimination to 119. The failure of the reaction to produce 119 has been attributed to the high strain energy of the product, which is estimated some 2 8 kcal/mol higher than that expected for two isolated cyclopropene units. ... 

The trans isomer turned out to be favored over the cis isomer by 41.8 kJmol at B3LYP/aug-cc-pvTZ level of theory. In both isomers the C—N—O moiety is strongly polarized. The charges are 4-0.24 e for both nitrogens and —0.50 and 0.51 e for both... 

In contrast, when the substitution pattern is reversed, i.e. the 2,5-fiirane unit is incorporated in the diamine moiety 25 and reacted with isophthaloyl dichloride (3), not only macrocycle 24, but also the two possible isomeric catenanes 26 and 27 are formed. This suggests that the isophthaloyl unit is a better guest or reacts quicker than the furanoyl moiety. The yields obtained for 26 (20%) and 27 (8%) indicate that the isophthaloyl-guest in the second macrocyclization prefers the west-side a) niche of the host 24. Both isomers, the in/out 26 and the out/out 27 furano catenane could be crystallized and their X-ray crystal structures were... 

The first enantiomer-selective polymerization was performed with propylene oxide (172) as a monomer [245], The polymerization was carried out with a ZnEt2/(+)-bor-neol or ZnEt2/(-)-menthol initiator system. The obtained polymer was optically active and the unreacted monomer was rich in (S)-isomer. Various examples are known concerning the polymerization and copolymerization of 172 [246-251 ]. A Schiff base complex 173 has been shown to be an effective catalyst In the polymerization at 60°C, the enantiopurity of the remaining monomer was 9% ee at 50% monomer conversion [250],... 

It has been reported that according to NMR spectra both m-isomers of cyclohexaoxathiazolidines 53 and 54 are in conformational equilibrium at room temperature, and isomer 53 is a ca. 1 1 mixture of the O-in and O-out conformers, and that there is a roughly 4 1 preference for the O-in 54a conformation in the isomer 54 (Equations 6 and 7) <1996ACS1036>. 

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