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Facile Synthesis of Bicyclic and Tricyclic Skeletons by Cycloisomerizations of Hept‐1‐en‐6‐ynes and 4,9‐Diheteradodeca‐1,11‐dien‐6‐ynes, Followed by [4 + 2] Cycloadditions
Author(s) -
van Boxtel Lonneke J.,
Körbe Stefanie,
Noltemeyer Mathias,
de Meijere Armin
Publication year - 2001
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200106)2001:12<2283::aid-ejoc2283>3.0.co;2-g
Subject(s) - chemistry , intramolecular force , cycloisomerization , bicyclic molecule , cycloaddition , methyl acrylate , tricyclic , regioselectivity , medicinal chemistry , palladium , stereochemistry , catalysis , organic chemistry , polymer , copolymer
Palladium‐catalyzed intramolecular cross coupling of various 4‐substituted hept‐1‐en‐6‐ynes, followed by intermolecular [4 + 2] cycloaddition with methyl acrylate and 2‐chloro‐2‐cyclopropylideneacetate yielded both all‐carbon and heteroanalogous bicyclic derivatives 8 , 9 , 18 , 19 , and 24 (24−71%). Cycloisomerization of the hydroxymethyl‐ and hydroxyethyl‐substituted hept‐1‐en‐6‐ynes 5 and 15 , followed by Diels−Alder reaction with methyl acrylate, occurred with intramolecular transesterification to give the tricyclic lactones 11 (37%) and 16 (15%), respectively. Tricyclic systems containing up to three heteroatoms could be obtained from the corresponding dodeca‐1,11‐dien‐6‐ynes, by palladium‐catalyzed cycloisomerization followed by intramolecular [4 + 2] cycloaddition. The scope and limitations of this single‐operation tricyclization were evaluated. Symmetrically disubstituted dienynes with two nitrogen or two oxygen atoms reacted efficiently (41−90%) in this way, producing 5‐6‐5 ring‐size combinations. Diastereoselectivities were poor in all cases (1:1 to 3.4:1). Unsymmetrically disubstituted dodeca‐1,11‐dien‐6‐ynes 44 and 48 underwent tricyclization with little or no regioselectivity to give 49 / 50 (7:3) and 51 / 52 (1:1).