Medium-sized bridged cyclophanes have attracted considerable interest because of their unusual conformational, chemical, and spectroscopic properties caused by deformation and strain in the aromatic ring and in the bridging ansa chain. [1] Among cyclophanes, meta-or paracyclophanes having dynamic planar chirality have generated much theoretical and synthetic interest as unique chiral molecules. In contrast, their regioisomer, that is, orthocyclophane (A) does not attract much attention owing to its less interesting topology and lack of planar chirality.[2] However, the introduction of a properly designed ansa chain, which can be on the outside of the plane of the benzene ring and decrease the flexibility of the molecule, may create stable planar chirality, even in simple orthocyclophanes. Herein we report the design and synthesis of the planar-chiral [7]orthocyclophanes 1 having an E alkene in the ansa chain, as well as a detailed stereochemical analysis and a demonstration of their utility in synthesis.Recently, we discovered a novel class of planar-chiral heterocycles (2) which consist of a bis(allylic) skeleton and the heteroatom X (X = O, NTs, SO n ; Ts= 4-toluenesulfonyl).[3] The chirality of these compounds originates from the presence of suitably located E and Z alkenes in the ninemembered ring.[4] On the basis of this stereochemical phenomenon, we anticipated that the orthocyclophane 1, in which the Z alkene of 2 is replaced by a benzene ring, may display planar chirality. It is also expected that 1 can achieve thermal stability, which 2 does not exhibit (see below). The details of the study are provided below.At the outset, we examined the synthesis of the nitrogencontaining orthocyclophane 1 aa (X = NTs, R = H) from the known diol 3 (Scheme 1). The Mitsunobu reaction of 3 and TsNHCO 2 Me proceeded with high group selectivity and provided the amide alcohol 4 as the only product in 78 % yield.[5] The Dess-Martin oxidation of the alcohol moiety of 4 followed by the Horner-Wadsworth-Emmons reaction and treatment with DIBAL provided the key intermediate (E)-5 in 71 % yield (three steps). The intramolecular Mitsunobu reaction of (E)-5 under a high dilution conditions (ca. 0.01m) provided the desired cyclic amide 1 aa in excellent yield (90 %). It should be noted that only a negligible amount of dimerized product (< 1 %) was formed in this reaction. The orthocyclophane 1 aa afforded a crystal suitable for X-ray analysis. The analysis reveals that the ansa chain is located on the outside of the plane of the benzene ring and both the benzene ring and alkene moieties of the ansa chain form chiral planes in the solid state (Scheme 1). [6] The existence of isolable enantiomers of 1 aa in solution was revealed by HPLC analysis using a chiral stationary column equipped with a CD spectropolarimeter. As shown in Figure 1, both enantiomers of 1 aa were successfully separated on an analytical as well as a semi-preparative scale.[7] The The Z isomer was separated by silica gel choromatography]; e) PPh 3 , DEAD, THF, À7...

Medium-sized bridged cyclophanes have attracted considerable interest because of their unusual conformational, chemical, and spectroscopic properties caused by deformation and strain in the aromatic ring and in the bridging ansa chain. [1] Among cyclophanes, meta-or paracyclophanes having dynamic planar chirality have generated much theoretical and synthetic interest as unique chiral molecules. In contrast, their regioisomer, that is, orthocyclophane (A) does not attract much attention owing to its less interesting topology and lack of planar chirality. [2] However, the introduction of a properly designed ansa chain, which can be on the outside of the plane of the benzene ring and decrease the flexibility of the molecule, may create stable planar chirality, even in simple orthocyclophanes. Herein we report the design and synthesis of the planar-chiral [7]orthocyclophanes 1 having an E alkene in the ansa chain, as well as a detailed stereochemical analysis and a demonstration of their utility in synthesis.Recently, we discovered a novel class of planar-chiral heterocycles (2) which consist of a bis(allylic) skeleton and the heteroatom X (X = O, NTs, SO n ; Ts= 4-toluenesulfonyl). [3] The chirality of these compounds originates from the presence of suitably located E and Z alkenes in the ninemembered ring. [4] On the basis of this stereochemical phenomenon, we anticipated that the orthocyclophane 1, in which the Z alkene of 2 is replaced by a benzene ring, may display planar chirality. It is also expected that 1 can achieve thermal stability, which 2 does not exhibit (see below). The details of the study are provided below.At the outset, we examined the synthesis of the nitrogencontaining orthocyclophane 1 aa (X = NTs, R = H) from the known diol 3 (Scheme 1). The Mitsunobu reaction of 3 and TsNHCO 2 Me proceeded with high group selectivity and provided the amide alcohol 4 as the only product in 78 % yield. [5] The Dess-Martin oxidation of the alcohol moiety of 4 followed by the Horner-Wadsworth-Emmons reaction and treatment with DIBAL provided the key intermediate (E)-5 in 71 % yield (three steps). The intramolecular Mitsunobu reaction of (E)-5 under a high dilution conditions (ca. 0.01m) provided the desired cyclic amide 1 aa in excellent yield (90 %). It should be noted that only a negligible amount of dimerized product (< 1 %) was formed in this reaction. The orthocyclophane 1 aa afforded a crystal suitable for X-ray analysis. The analysis reveals that the ansa chain is located on the outside of the plane of the benzene ring and both the benzene ring and alkene moieties of the ansa chain form chiral planes in the solid state (Scheme 1). [6] The existence of isolable enantiomers of 1 aa in solution was revealed by HPLC analysis using a chiral stationary column equipped with a CD spectropolarimeter. As shown in Figure 1, both enantiomers of 1 aa were successfully separated on an analytical as well as a semi-preparative scale. [7] The Scheme 1. Synthesis and X-ray analysis of 1 aa: a) TsNHCO 2 Me, PPh 3 , DEAD, TH...

Planar chiral oxa-[7]orthocyclophene 1a was designed and synthesized with two different synthetic routes. X-ray crystallographic analyses of 1a and its platinum complex revealed a highly distorted ring structure and the absolute stereochemistry of 1a, respectively. Epoxidation and [2,3]-Wittig rearrangement of 1a provided with central chiral molecules, without the loss of enantiomeric purity.