Premium
Herstellung neuer polycyclischer Verbindungen durch intramolekulare Diels ‐ Alder ‐Reaktionen von Cyclohexa‐2,4‐dien‐1‐on‐Abkömmlingen
Author(s) -
Greuter Hans,
Schmid Hans,
Fráter György
Publication year - 1977
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19770600526
Subject(s) - chemistry , intramolecular force , pericyclic reaction , medicinal chemistry , isomerization , diels–alder reaction , ether , intramolecular reaction , sigmatropic reaction , bromide , ketone , stereochemistry , organic chemistry , catalysis
Synthesis of new polycyclic compounds by means of intramolecular Diels ‐ Alder reactions of cyclohexa‐2,4‐dien‐1‐one derivatives Thermal rearrangement of mesityl penta‐2,4‐dienyl ether ( 1 ), consisting of the isomers E (93%) and Z (7%), furnished, besides mesitol, the two mesityl penta‐1,3‐dienyl ethers 2 (24%) and 3 (3%), and the two tricyclic ketones 4 (4,5%) and 5 (12,5%) ( Scheme 1 ). A probable mechanism for this formation of 2 involves a [1,5]‐hydrogen shift in ( Z )‐ 1 . Isomerisation of ( E )‐ 1 to ( Z )‐ 1 at 145° occurs via reversible sigmatropic [3,3]‐ and [5,5]‐rearrangements of ( E )‐ 1 to the cyclohexadienones 38 and 39 respectively (see Chapter A p. 1710, and Scheme 15 ). Formation of 3 from either ( Z )‐ 1 or 2 is rationalized by a series of pericyclic reactions as outlined in Chapter A and Scheme 16 . The tricyclic ketones 4 and 5 are undoubtedly formed by internal Diels ‐ Alder reactions of the 6‐pentadienyl‐cyclohexa‐2,4‐dien‐1‐one 6 ( Scheme 2 ). In fact, at 80° 6 is converted into 4 (5%) and 5 (35%). At 80° the cyclohexadienone derivative 7 furnished the corresponding tricyclic ketones 8 (15%) and 9 (44%) ( Scheme 2 ). 5 and 9 contain a homotwistane skeleton. 8 and 9 are easily prepared by reaction of sodium 2,6‐dimethylphenolate with 3‐methyl‐penta‐2,4‐dienyl bromide at ambient temperature, followed by heating, and finally separation by cristallization and chromatography. The cyclohexadienones 6 and 7 have mainly ( E )‐configuration. Here too ( E ) → ( Z ) isomerization is a prerequisite for the internal Diels ‐ Alder reaction, and this partly takes place intramolecularly through reversible Claisen and Cope rearrangements ( Scheme 17 ). On the other hand, experiments in the presence of 3,5‐d 2 ‐mesitol have shown ( Table 1 ) that intermolecular reactions, involving radicals and/or ions, are also operating (see Chapter B , p. 1712). Two different modi (I and II) exist for intramolecular Diels ‐ Alder reactions ( Scheme 18 ). Whereas only modus I is observed in the cyclization of 5‐alkenyl‐cyclohexa‐l,3‐dienes, in that of (2)‐cyclohexadienones 6 and 7 ( Scheme 2 ) both modi are operating. Only in modus 11‐type transitions is the butadienyl conjugation of the side chain retained, so that modus 11‐type addition is preferred (Chapter C p. 1716). Analogously to the synthesis of the tricyclic ketones 4 , 5 , 8 and 9 , the tricyclic ketone 15 ( Scheme 4 ) and the tetracyclic ketone 11 ( Scheme 3 ) are prepared from mesitol, pentenyl bromide and cycloheptadienyl bromide, respectively. From the polycyclic ketones derivatives such as the alcohols 16 , 17 , 18 , 19 , 23 , 24 and 25 ( Schemes 9 and 11 ), policyclic ethers 20 , 21 , 22 and 26 ( Scheme 10 ), epoxides 30 , 32 ( Scheme 13 ), diketones 31 , 33 ( Scheme 13 ) and ether‐alcohols 35 and 36 ( Scheme 14 ) have been prepared. Most of these conversions show high stereoselectivity.