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.