High Acceleration and Improved Diastereoselectivity of Intramolecular Ene‐Type Reactions by Diethylaluminum Chloride. Preliminary Communication

Abstract

SummaryThe pyrrolidines 2 and 10 were obtained by thermal ene-reactions at +70" and + 180" from the (Z)-4-aza-1,6-diene I and from the (E)-4-aza-1,6-diene 9 in the ratios of 75: 25 and 50: 50, respectively. On the other hand, these cyclizations proceeded readily in the presence of diethylaluminum chloride at -78" and -35" giving in high yield the trans-pyrrolidine 2 from 1 with 100% and from 9 with 89% diastereoselectivity .Recently, we have reported a simple synthesis of the racemic amino acid 3 by the sequence 1 + 2 -+ 3 (Scheme I ) [ 11. In conjunction with our systematic studies of intramolecular ene reactions [2] we felt it worthwhile to re-examine the key step 1 -2 in more detail. One important question was the extent to which the unusual 75% diastereoselectivity in favour of the trans-product 2') depends on the enophile geometry in 1.was easily accessible viu the previously described preparation of the (Z)-acrylate 6 (J(AB)= 12 Hz) [3] (treatment of the cis-P-chloroacrylate 4Thermal cyclization of 1 furnished a 3:l mixture of 2 and its cis-isomer 10 as we found by 'H-NMR. analysis of the cyclization mixture (vide infru) and of the aminoacid mixture obtained together with (k )-3.

Asymmetric total synthesis of naturally occurring (R)-(–)-enantiomer of tylophorine via intramolecular double Michael reaction

“…); -258.11' (c 0.36 in methanol), whose IR and NMR spectra were identical with those of the sample prepared by method (a). The acid (14) was converted, as the case of method (a), into (-)tylophorin-Pone (15), identical with an authentic sample in all respects.…”

Selectivity: A Key to Synthetic Efficiency

“…27) (37). Use of such weak secondary interactions has had remarkable success in related thermal processes (39,40).…”

Asymmetric Diels‐Alder Reactions of Neopentyl‐Ether‐Shielded Acrylates and Allenic Esters: Syntheses of (−)‐Norbornenone and (−)‐β‐Santalene

“…Its value is illustrated by application to the syntheses of enantiomerically pure building blocks and also of a natural product. The starting point for this work was the encouraging chiral induction observed with Lewis-acid-promoted ene-type cyclizations (1h2) [4] and [4+2] cycloadditions (3-4) [5] of 8-phenylmenthyl enoates …”