Participation of 19-ester groups in hypobromous acid additions to 2,3- and 5,6-unsaturated steroids

1979 ◽  
Vol 44 (5) ◽  
pp. 1483-1495 ◽  
Author(s):  
Pavel Kočovský ◽  
Václav Černý ◽  
Miroslava Synáčková
Keyword(s):  
Intramolecular Interaction ◽  
Ester Group ◽  
Carbonyl Oxygen ◽  
Cyclic Ether ◽  
Normal Reaction ◽  
Neighboring Group ◽  
Group Participation ◽  
Hypobromous Acid ◽  
Ether Oxygen ◽  
Neighboring Group Participation

Hypobromous acid action upon the 2,3-unsaturated acetoxy derivative Ia results in the formation of two products, the bromohydrin IVa and the cyclic ether VI as a product of the participation of ether oxygen of the ester group. Both these compounds are formed from the 2α,3α-bromonium ion XIIIa. Under the same conditions the 5,6-unsaturated 19-acetoxy derivative IIa afforded a mixture of the following products: Bromohydrin Xa as the product of a normal reaction course and the isomeric bromohydrin VIIa arising by intramolecular interaction with the carbonyl oxygen of the 19-acetoxy group. Both these compounds are formed from the 5α,6α-bromonium ion XVIIIa. The epimeric 5β,6β-bromonium ion XVIIa gives rise to the bromohydrin XIa. The mechanism of these reactions, difference in behavior of both olefins I and II and the competition between ambident neighboring group participation and external nucleophile attack is discussed.

Participation of 19-ester groups in the cleavage of 2α,3α- and 5α,6α-steroid epoxides. A case of competition between participation and external nucleophile attack

1979 ◽  
Vol 44 (5) ◽  
pp. 1496-1509 ◽  
Author(s):  
Pavel Kočovský ◽  
Václav Černý
Keyword(s):  
Perchloric Acid ◽  
Hydrobromic Acid ◽  
Ester Group ◽  
Carbonyl Oxygen ◽  
Cyclic Carbonate ◽  
Cyclic Ether ◽  
Normal Reaction ◽  
Neighboring Group ◽  
Ether Oxygen ◽  
The Difference

Acid cleavage of the acetoxy epoxide IIIa with aqueous perchloric acid or hydrobromic acid gave two types of products, i.e. the diol Va or the bromohydrin VIa, and the cyclic ether VIII. The latter compound arises by participation of ether oxygen of the ester group. On reaction with perchloric acid the epoxide IVa gave the diol XIIIa as a product of a normal reaction and the isomeric diol Xa as a product arising by intramolecular participation of the carbonyl oxygen of the 19-acetoxy group. Participation of the 19-ester group is confirmed by the formation of the cyclic carbonate XI when the 19-carbonate IVb is treated analogously. On reaction with hydrobromic acid, the epoxide IVa gave solely the bromohydrin XIVa as a product of the normal reaction course. Discussed is the similarity of these reactions with electrophilic additions to the related 19-acetoxy olefins I and II, the mechanism, the difference in behavior of both epoxides III and IV, the dependence of the product ratio on the nucleophility of the attacking species, and the competition between participation of an ambident neighboring group and an external nucleophile attack.

Synthesis of 14-deoxy-14α-strophanthidin

1980 ◽  
Vol 45 (11) ◽  
pp. 2998-3007 ◽  
Author(s):  
Pavel Kočovský
Keyword(s):  
Acetic Acid ◽  
Hydroxy Group ◽  
Cyclic Ether ◽  
Hydroxy Derivative ◽  
Neighboring Group ◽  
Step Process ◽  
Group Participation ◽  
Hypobromous Acid ◽  
Characteristic Features ◽  
Neighboring Group Participation

A seventeen step synthesis of 3β,5-dihydroxy-19-oxo-5β,14α-card-20(22)-enolide (II, title compound) from 3β-benzoyloxy-5-pregnen-20-one (IV) is described. Characteristic features of this approach are the protection of the 19-hydroxy group as methyl ether, recovery of the hydroxyl and the introduction of 5β-hydroxyl on the basis of neighboring group participation. The 19-hydroxy group was regenerated in XIV by a two-step process: Addition of hypobromous acid to the 5,6-double bond leads to the 5α,6α-bromonium ion XV, which is cleaved with 5(O)n participation of the 19-methoxyl group to the cyclic ether XVI, the latter being converted to the 19-hydroxy derivative XVII by treatment with zinc and acetic acid. The 5β-hydroxy group was introduced by hypobromous acid addition to the 5,6-unsaturated 19-formate XVIII which proceeds with 6(O)π,n participation of the formate group (XVIII → XIX → XX).

Neighboring group participation in hypobromous acid addition to 19-substituted 5α-cholest-1-enes and in acid cleavage of their epoxy analogs

1982 ◽  
Vol 47 (11) ◽  
pp. 3062-3076 ◽  
Author(s):  
Václav Černý ◽  
Pavel Kočovský
Keyword(s):  
Neighboring Group ◽  
Group Participation ◽  
Acid Addition ◽  
Acid Cleavage ◽  
Hypobromous Acid ◽  
Neighboring Group Participation

Reactions of the title compounds (bearing an OH, OCH3 or OCOCH3 group at C(19)) involve 5(O)n, 7(O)π,n-participation by the 19-substituent or attack by an external nucleophile. The 6(O)π,n-participation does not occur. The behavior of 1,2-unsaturated (or epoxidated) compounds has been compared with the earlier described 2,3-unsaturated or epoxidated analogs. The 1,2-type is genarally less prone to participation. The reasons for this behavior are discussed.

Mechanism of acid cleavage of some steroid epoxides. Competition between neighboring group participation and external nucleophile attack

1982 ◽  
Vol 47 (1) ◽  
pp. 124-129 ◽  
Author(s):  
Pavel Kočovský ◽  
František Tureček ◽  
Václav Černý
Keyword(s):  
Perchloric Acid ◽  
Cyclic Ether ◽  
Oxirane Ring ◽  
Neighboring Group ◽  
Group Participation ◽  
Acid Cleavage ◽  
Neighboring Group Participation

The mechanism of perchloric acid cleavage of epoxides I and II was established on the basis of experiments using H2 18O. The 2α,3α-epoxide I gave two products: the cyclic ether V (60%) arising by 5(O)n participation of the 19-acetoxyl and the diol VI (40%). The latter compound is formed by two mechanisms: 1) By direct cleavage of the oxirane ring with H2 18O as external nucleophile and 2) by 7(O)π,n participation via the ion III. Under the same conditions the 5α,6α-epoxide II yielded two diols: The diequatorial diol VIII (96%) arising by 6(O)π,n participation and the diaxial diol IX which is again formed by both direct cleavage of the oxirane ring with H2 18O and by 7(O)π,n participation via the intermediate ion X. The competition of several mechanisms is discussed.

Participation of 19-substituents in acid cleavage of steroidal 3α,4α- and 4α,5α-epoxides

1980 ◽  
Vol 45 (11) ◽  
pp. 3199-3209 ◽  
Author(s):  
Pavel Kočovský ◽  
Václav Černý
Keyword(s):  
Hydrobromic Acid ◽  
Acid Treatment ◽  
Cyclic Ether ◽  
Acetoxy Group ◽  
Limited Extent ◽  
Neighboring Group ◽  
Group Participation ◽  
Acid Cleavage ◽  
Neighboring Group Participation ◽  
External Attack

Participation of the 19-methoxy and 19-acetoxy group in 3α,4α- and 4α,5α-epoxides IIIc, IVb,c on treatment with aqueous perchloric or hydrobromic acid is investigated and compared with acid treatment of structurally similar 19-substituted 6α,7α- and 5α,6α-epoxides V and VI and with the behavior of analogous 3α,4α- and 4α,5α-bromonium ions. The 3α,4α-epoxides III react readily with 5(O)n participation. The reaction is practically quantitative on perchloric acid treatment. Under the same conditions, the 19-methoxy-4α,5α-epoxide IVb suffers mainly external attack leading to the diol XIb. The neighboring group participation is solely a 5(O)n process giving rise to the cyclic ether X. The 19-acetoxy-4α,5α-epoxide IVc reacts predominantly with participation of the ambident acetoxy group. This reaction is exclusively a 6(O)π,n process affording the diol XVI. External attack proceeds to a limited extent to give the isomeric diol XIc. In this respect the latter compounds react quite analogously to 5α,6α-epoxides VI and 4α,5α- and 5α,6α-bromonium ions bearing 19-acetoxyl.

Neighboring group participation in electrophilic additions: The role of Markovnikov and Fürst-Plattner rule in hypobromous acid addition to 5,6-unsaturated cholestane derivatives

1983 ◽  
Vol 48 (12) ◽  
pp. 3618-3628 ◽  
Author(s):  
Pavel Kočovský
Keyword(s):  
Methyl Ether ◽  
Hydroxyl Group ◽  
Unsaturated Alcohol ◽  
Neighboring Group ◽  
Group Participation ◽  
Acid Addition ◽  
Hypobromous Acid ◽  
Neighboring Group Participation ◽  
Electrophilic Additions

On reaction with hypobromous acid, the unsaturated alcohol IIIa yields the diequatorial bromo epoxide XIX arising from the 5α,6α-bromonium ion XVIIIa on cleavage at C(5) by 19b-hydroxyl group with 6(O)n participation. By contrast, the bromonium ion XVIIIb generated from the unsaturated methyl ether IIIb is cleaved by water as external nucleophile to yield the unstable diaxial bromohydrin XX which undergoes cyclization to the oxirane derivative XXI. A comparison with the reaction course in homologs of the type I and II permits the conclusion that the change in regioselectivity, generally possible outcome of the 5(O)n participation, is only possible for the 6(O)n process if the participating group is a hydroxyl.

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