Modeling the Effect of Substitution on the Pb(OAc)₄ Mediated Oxidative Cleavage of Steroidal 1,2-Diols

Abstract

[reaction: see text] We comment on the effects of angular substitution on the outcome of a Pb(OAc)4 (LTA) mediated heterodomino reaction, with selected bicyclic unsaturated 1,2-diols, which is considered to proceed through a series of transformations in a single vessel. The first two, oxidative and pericyclic, are followed by the key step, an electrophilic addition of LTA to the olefin, responsible for the course of the domino process. In this study, the electrophilic addition of LTA to the double bond has been modeled with B3LYP, where the 6-31G* basis set is used for C, O, and H atoms and the LANL2DZ method is used for Pb. The modeling in the gaseous phase and in solution has revealed the concerted nature of the addition of LTA to the double bond of the intermediate. The fact that LTA adds from the same side as the substituent R, for R=H and from the opposite side when R=CH3 has been attributed to steric hindrance, which causes deformation of the olefinic intermediate.

Modular Construction of Topologically Complex Polycyclic Acetals by Tether‐Controlled Domino Reactions

“…A synopsis of the possible sequence of events is provided in Scheme . Despite the fact that the data do not permit an unambiguous conclusion to be drawn about the sequence of events portrayed in Scheme , the simplest scenario is that acetate attack at C2 is not a concerted process (intramolecular delivery as in ii , Scheme ) but rather occurs in an intermolecular manner 20. Yet, there is a notable exception to the domino reactions mentioned above (Scheme ), relating to the behavior of substrate diol 1′c (and half‐cascade 2′c ) under microwave heating.…”

Stimulating excursions into organolead chemistry: modular domino sequences triggered by oxidative cleavage

“…6). 37 Calculated energy barriers for a concerted mechanism of Pb(OAc) 4 attack on the olefin were found to be 35-40 kcal/mol compared to 102 kcal/mol for ionic and 54 kcal/mol for radical mechanisms. As portrayed in Figure 6, complexity is first governed by the sense of metal attack on the olefin i/ii and further modulated by geometry in the transient organolead intermediate iii/iv.…”

“…The results obtained for Pb(OAc) 4 induced domino reactions show that there is a dual pathway to high molecular complexity with a strong dependence on the nature of the angular substituent in the starting domino probe. 37 The ester derivatives as well as the alkyl, olefin, or any other than angular hydrogen containing 1 st generation domino probes appear to go exclusively through the ring-expansion via i, while ether-linked derivatives undergo facile cyclization via ii (the oxonium path) either at rt or under microwave heating (Scheme 34).…”