Metal-Induced Reductive Cleavage Reactions:  An Experimental and Theoretical (MNDO) Study on the Stereochemical Puzzle of Birch and Vinylogous Birch Processes

Abstract

The stereochemical puzzle posed by the lithium-promoted Birch and vinylogous Birch reductive cleavage of unsaturated benzyl ethers (BICLE; takes place with retention of configuration of the sensitive 2Δ double bond) and the corresponding cinnamyl analogs (VIBICLE; gives rise to ca. 2.5:1 E:Z mixtures) has been approached by experimental and theoretical means. NMR experiments indicate that the π-type organolithium compounds resulting from these reactions do not form observable mixed aggregates with the lithium silyloxide species generated alongside in the reaction and do not undergo observable isomerization at the temperature of operation. A simplified model for contact, solvent-separated, and isolated ion pairs has allowed us to evaluate these complex reactions in great detail from a theoretical viewpoint, using the MNDO semiempirical method. Relevant features that come out from these comprehensive studies, for which we have employed lithium naphthalenide (LiNaph) or lithium benzenide (LiBenz) as promoters, are as follows: (1) the lowest energy routes for cleavage are those involving contact ion pairs (CIPs) in which the lithium counterion plays a key role by acting as a handle (Lewis acid) to which the leaving group -OR adheres prior to detachment; (2) the different haptomeric structures which reside (local minima) in the potential hypersurface of either the so-called radical anion or the dianion routes show that haptomeric activation is key to understanding cleavage of the C−O bond which, eventually, takes place as a syn β elimination of LiOR; and (3) reductive cleavage of unsaturated benzyl ethers (BICLE) involves transient cation/anion radicals which undergo cleavage and subsequent reduction to the final organolithium with retention of configuration, in accordance with experiment, whereas that of vinylogous cinnamyl ethers (VIBICLE) involve transient dianion/dication species resulting from long-lived cation/anion radicals. In good qualitative agreement with experiment, MNDO finds two diastereomeric routes (ΔΔG* = 0.2 kcal/mol) for cleavage of (appropriately substituted) cinnamyl ethers, but only one for cleavage of the unsaturated benzyl analogs.

Electrostatic and Electrophilic Catalysis in the Reductive Cleavage of Alkyl Aryl Ethers. The Influence of Ion Pairing on the Regioselectivity

“…On the other hand, it has been also recently demonstrated that in some particular “heterolytic” mesolytic cleavage of ethers, lithium plays a key role in promoting the cleavage by acting as an internal Lewis acid in assisting the departure of the leaving group …”