Synthesis of Optically Active Bis(2‐oxazolines): Crystal Structure of a 1,2‐Bis(2‐oxazolinyl)benzene ZnCl₂ Complex

Abstract

Dinitriles (5-7. 12, 13) react with enantiomerically pure 0-required for a conformational interconversion of zinc dichloramino alcohols (8 -11.17) under zinc chloride catalysis to give ide complex 23e was determined by variable-temperature 'Hoptically active C2-symmetric bis(oxazo1ines). 1,2-Bis(Z-ox-NMR studies. An X-ray structure analysis was performed with azolin-2-y1)benzenes 1 a -e are obtained under mild reaction the substituted [ 1.2-bis(2-oxazolinyl)benzene]zinc dichloride conditions. 'H-NMR spectroscopy indicates the formation of complex 23 a. 1 : 1 complexes 23 of these compounds with ZnC12. The energy Optically active oxazolines have been extensively used as valuable auxiliaries in asymmetric synthesis 2! They can effect efficient chirality transfer from the heterocycle to newly formed bonds, thereby generating new centers of chirality with high asymmetric induction. Oxazolines have also been found in many microbial metal chelators such as vibriobactin, mycobactin, and parabactin3! In these cases they are incorporated into extremely strong multidentate metal complexes, illustrating the high chelating ability of this moiety. Based on these properties, optically active oxazolines have been used as chiral ligands for transition metals in asymmetric catalysis4! During our studies of new bidentate ligands for enantioselective transition-metal catalysis5), we have envisioned that C2-symmetric homochiral bis(2-oxazoliny1)benzenes of type 1 and 2 might be effective ligands for affecting asymmetric catalysis.Compounds of type 2 have previously been prepared by dehydration of 1,3-bis(ben~oylamino)benzenes~~~~~ with thionyl chloride or by modified Pinner reactions (diimidate formation of 1,3-dinitriles, followed by reaction with amino alcohol^)^). However, ortho-substituted benzenes of type 1 are not easily accessible by these routes. They have only been synthesized under vigorous reaction conditions. For example, dehydration of 1,2-bis(benzoylamino) derivatives to 1,2-bis(2-oxazolin-2-yl)benzenes (type 1) requires high temperatures (100-170°C) and strongly acidic conditions (30% SO3 in 70% sulfuric acid)". The Pinner method fails because 1,2-dinitriles can only be converted to stable monoimidate salts (3). The second cyano group of 3 is inert, and bisimidates are not formed9). r OR 3 4In 1974 Witte and Seeliger reported on a procedure for the preparation of mono-and bis(2-oxazolines) by direct reaction of nitriles with amino alcohols in the presence of catalytic amounts of metal saltsloaJ. However, attempts to use phthalonitrile and 2-aminoethanol gave exclusively 2,3-dihydro-1,3-bis(2-hydroxyethylimino)-1H-isoindol (4); no 1,2-bis(2-oxazolinyl) derivatives could be obtained. The stereochemical course of this reaction was not examined. Synthesis of Bis(2-oxazolines)By a careful reinvestigation of Witte and Seeliger's metalcatalyzed oxazoline synthesis, we now demonstrate that a variety of substituted optically active bis(2-oxazolinyl) derivatives can readily be prepared under mild reaction conditions. We obtaine...

Studies on the Bisoxazoline‐ and (−)‐Sparteine‐Mediated Enantioselective Addition of Organolithium Reagents to Imines

“…In the weakly coordinating solvent toluene, bidentate complexation of MeLi by the nitrogen lone pairs of the bisoxazoline auxiliary is assumed, (12ac•MeLi). This conjecture is corroborated by the X-ray structures of the copper, [66] zinc, [67] and palladium complexes [27a] with very similar bisoxazolines and the fact that the doubly oxygen-coordinated structure is computationally far less stable (MNDO: 5.3; PM3: 12.2 kcal/mol). The bisoxazoline system is strongly distorted in MNDO forming a cavity similar to the experimental zinc structure [67] and less so in PM3 thus resembling the planar copper [66] and palladium geometries.…”

Methyl-2-Thienylketopolymethyleneoxyphenyl Derivatives of Alkyl-Substituted 4,5-Dihydro-Oxazoles with Anti-Human Picornavirus Activity

“…4) by treatment with 4-(4,S-dihydro-2-oxazolyl)phenols 11a-f, 12b and ATEE monohydrate (14), respectively, according to previously described procedures (Massa et al, 1991(Massa et al, , 1995. 4-(4,S-Dihydro-4-(or 5)substituted-2-oxazolyl)phenols 11a-f were obtained by reaction of 4-hydroxybenzonitrile with the appropriate amino alcohols in the presence of catalytic amounts of zinc dichloride in refluxing chlorobenzene, according to the Witte and Seeliger procedure (Witte and Seeliger, 1974) as partially modified by Balm (Bolm et et., 1991) (Fig. S).…”

Mechanism of enantioselective protonation of an enolate in the presence of a chiral phenolic additive

“…5 [␣] D 298 −64.9 (c = 4.6 toluene)} as a chiral scaffold for this enantioselective protonation study primarily because of its mildly acidic phenolic O-H coupled with the potential for additional coordination 6,7 (via the sp 2 nitrogen of the oxazoline) to the lithium of the enolate to assist regioselective C-protonation. 1 There is also some evidence that mildly acidic chelating proton sources (such as carboxylic acids 4,8,9 and phenols 7 ) do promote regioselective C-protonation of enolates.…”