Planar‐Chiral [7]Orthocyclophanes

Abstract

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...

Stereochemical study on planar‐chiral cyclic molecules using polysaccharide‐based column chromatography

“…Conditions of HPLC for 2ba 24 : Analytical HPLC (column: CHIRALCEL OD‐H [4.6 mm × 250 mm], eluent: hexane/ i PrOH = 3:7, flow rate: 0.5 ml/min, detection: UV 254 nm, temperature: rt): t R = 15.7 min for ( S )‐isomer, 44.1 min for ( R )‐isomer.…”

“…Conditions of HPLC for 2bb 24 : Analytical HPLC (column: CHIRALCEL OD‐H [4.6 mm × 250 mm], eluent: hexane/ i PrOH = 3:7, flow rate: 0.5 ml/min, detection: UV 254 nm, temperature: rt): t R = 21.8 min for ( S )‐isomer, 48.7 min for ( R )‐isomer; preparative HPLC (column: CHIRALCEL OD‐H [20 mm × 250 mm], eluent: hexane/EtOH = 3:7, flow rate: 8.0 ml/min, detection: UV 254 nm, temperature: rt): t R = 18.3 min for ( S )‐isomer, 29.5 min for ( R )‐isomer.…”

“…To address this issue, column chromatography using a chiral stationary phase (chiral chromatography) is useful and efficient. In this review article, we wish to describe the important role of chiral chromatography using a polysaccharide‐based chiral selector 7–17 in our study of planar‐chiral heterocycles 1 – 3 , 18–26 nine‐membered cyclic ketone 4 , and its enol ester 5 , 27 , 28 along with a recent advancements in the screening of chiral columns, and the utility of Pt‐complexation for a detailed stereochemical study 29 …”

Medium‐Sized‐Ring Analogues of Dibenzodiazepines by a Conformationally Induced Smiles Ring Expansion

“…1 H NMR analyses of 4 a – l showed diastereotopic signals for the methylene groups within the ring, thus indicating that these heterocycles adopt chiral ground states whose enantiomeric conformations interconvert slowly on the NMR time scale . We determined the rate constants for interconversion of the enantiomers ( k enant ) of 4 a – d and 4 l by variable‐temperature exchange spectroscopy (VT‐EXSY), as summarized in Table (see the Supporting Information for details).…”

Recent Functionalizations of Primary Sulfonamides

“…It is not surprising that N-alkylated sulfonamides can be converted into N-acylsulfonamides via oxidation, though there have been just a few publications since the first report in 1983, in which substrates were oxidized by silica gel supported permanganate salts. 168 Other published oxidative methods include ruthenium tetraoxide catalyzed indirect electrooxidation in a saturated sodium chloride-acetone system, 169 aerobic oxidation using palladium-copper catalysts in the presence of carbon monoxide, 170 exothermic oxidation with chromyl acetate, 171 radical oxidation with hypervalent tert-butylperoxyiodanes, 172,173 ruthenium trichloride catalyzed oxidation with sodium periodate, 174,175 Rh 2 (cap) 4 -catalyzed benzylic oxidation, 176 acetic anhydride catalyzed oxidation by PCC, 177 aerobic oxidation with a TBHP/manganese triacetate system, 178 chromium trioxide catalyzed oxidation by periodic acid, 179 copper(II) sulfate mediated oxidation with potassium permanganate, 180,181 ruthenium(IV) oxide catalyzed oxidation with sodium periodate, 182 and benzylic oxidation with sodium chlorite. 183…”