High Asymmetric Induction in Lewis Acid‐Promoted Intramolecular Ene‐Type Reactions: A diastereo‐ and enantioselective synthesis of (+)‐α‐allokainic acid. Preliminary Communication

Abstract

SummaryThe monocyclic amino diacid (+)-a-allokainic acid 1 has been prepared enantioselectively from the ester of cis-P-chloroacrylic acid and (-)-8-phenylmenthol by a series of four synthetic operations in over 15% yield. The crucial step is the intramolecular 'ene-type' reaction of the (a-diene 4 which on treatment with a mild Lewis acid undergoes a highly accelerated, dia-and enantiostereoselective cyclization to give the pyrrolidines 6 and 7 in a ratio of 95: 5 (Scheme 3). Subsequent ester hydrolysis regenerates the auxiliary chiral alcohol. Similar cyclization of the (E)-diene 5 furnished a 15: 85 mixture of 6 and 7 showing an efficient reversal of the optical induction by variation of the enoate geometry.(+)-a-Allokainic acid, isolated from Digenea simplex AG., has been assigned structure 1 on the basis of chemical, chiroptic and X-ray evidence [l]. In the preceding communication we have described stereospecific routes to the (Z)-and (a-dienes 2 (R = Et) and their efficient diastereoselective cyclization to the truns- We only know about one study allowing recyclization of the chirality directing group which deals with the Lewis-acid catalyzed addition of menthylglyoxalate to 1-pentene; the corresponding adducts were obtained in only modest optical yields in spite of wide variations of temperature, solvent and catalyst [4]. IR., 'H-NMR. (CDCI3) and MS. are in full agreement with the assigned structure. 2,

High Asymmetric Induction in Conjugate Additions of RCu · BF3 to Chiral Enoates. Preliminary communication

“…The particularly smooth reaction may be attributed to a transition state A [12] or B implying either a synplanar or antiplanar C=C/C=O-arrangement. In context with asymmetric ene [ 131 and cycloaddition reactions [ 14-161 we assume that enoates of secondary alcohols prefer a conformation where the C=O is anti-') *) Reviews [ 11.…”

Mit der Eberesche vom Heimatlied zur Frühstücksmagarine

“…Oppolzer et al. continued the work on kainic acid and succeeded in the first asymmetric synthesis of (+)‐allokainic acid in a series of four synthetic operations with 15 % overall yield (Scheme ) 31. Initially the cyclization was tried on menthyl ester 40 , which was prepared as per an earlier method 32.…”

Amide acetal Claisen rearrangement in the synthesis of mesembrane alkaloids

“…The amide acetal Claisen rearrangement 1-3 that follows the reaction of amide acetals with allylic alcohols has been applied to the synthesis of the mesembrane alkaloids (-)-mesembranone 39, rac-O-methyljoubertiamine and j~ubertiamine.~ In order to study this rearrangement and the scope of its synthetic applications, we synthesized a number of allylic alcohols (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) and achiral (12,13) as well as chiral (14, 15) amide acetals, which we used as substrates in the amide acetal Claisen rearrangement.…”