In line with the principles of "green" chemistry, organocatalysis seeks to reduce energy consumption and to optimize the use of the available resources, aiming to become a sustainable strategy in chemical transformations. Nevertheless, during the last decade diverse experimental protocols have made organocatalysis an even "greener" alternative by the use of friendlier reaction conditions, or via the application of solvent-free methodologies, or through the design and synthesis of more selective catalysts, or via the development of multicomponent one-pot organocatalytic reactions, or by the recycling and reuse of organocatalysts, or by means of the application of more energy-efficient activation techniques, among other approaches. In this feature article we review some of the remarkable advancements that have made it possible to develop even more sustainable asymmetric organocatalyzed methodologies.
Ab initio calculations, within the framework of density functional theory, were carried out on cyclohexane, 1,3-dioxane, 1,3-dithiane, 1,3-oxathiane, and 1,3-diazane. The one-bond 13 C-1 H NMR coupling constants were estimated according to the recently proposed theory by Salahub, D. R. Chem. Phys. Lett. 1994, 221, 91]. No correlation between one-bond 13 C-1 H spin-spin coupling constants and the corresponding C-H bond distances was found. The direction of the Perlin effect, defined as the difference between the axial minus the equatorial one-bond C-H coupling constants, is correctly predicted by this methodology for all cases with the exception of one methylene group in 1,3-oxathiane. Thus, in general, the methodology is capable of reproducing subtle properties that are driven by stereoelectronic interactions.
The
first systematic study of the intramolecular α-effect,
both in the stable ground-state structures and in the high-energy
intermediates, was accomplished using the anomeric effect as an internal
stereoelectronic probe. Contrary to the expectations based on
the simple orbital mixing model, the lone pairs in a pair of neutral
directly connected heteroatoms are not raised in energy to become
stronger donors toward adjacent σ- and π-acceptors. Instead,
the key n(X‑Y)→σ*C‑F interactions (X,Y = O,N) in the “α-systems”
(both acyclic and constrained within a heterocyclohexane frame) are
weaker than nX→σ*C‑F interactions in “normal” systems. Surprisingly, polar
solvent effects increase the apparent magnitude of α-effect
as measured via increase in the anomeric stabilization. This behavior
is opposite to the solvent dependence of normal systems where the
anomeric effect is severely weakened by polar solvents. This contrasting
behavior reflects the different balance of electrostatic and conjugative
interactions in the two types of anomeric systems: the α-systems
suffer less from the unfavorable orientation of bond dipoles in the
equatorial conformer, a destabilizing electrostatic effect that is
shielded by the polar environments. A weak α-effect is brought
to life when the buttressing α-heteroatom bears a negative charge.
However, electrostatic components mask the role of stabilizing orbital
interactions. In contrast, the increased electron demand in carbocations
and related electron-deficient TS- like structures
does not lead to activation of the α-effect. As a consequence,
we observed that ethers are better radical- and cation-stabilizing
groups than peroxides. The latter finding should have significant
implications for understanding the mechanistic complexity associated
with the interaction of carbonyl compounds with hydroperoxides and
H2O2 in acidic media, as such reactions involve
α-cationic intermediates.
Cyclohexane (1), oxygen-, sulfur-, and/or nitrogen-containing six-membered heterocycles 2-5, cyclohexanone (6), and cyclohexanone derivatives 7-16 were studied theoretically [B3LYP/6-31G(d,p) and PP/IGLO-III//B3LYP/6-31G(d,p) methods] to determine the structural (in particular C-H bond distances) and spectroscopic (specifically, one bond (1)J(C-H) NMR coupling constants) consequences of stereoelectronic hyperconjugative effects. The results confirm the importance of n(X) --> sigma*(C-H)(app) (where X = O, N), sigma(C-H)(ax) --> pi*(C=O), sigma(S-C) --> sigma*(C-H)(app), sigma(C-S)-->sigma*(C-H)(app), beta-n(O) --> sigma*(C-H), and sigma(C-H) --> sigma*(C-H)(app) hyperconjugation, as advanced in previous theoretical models. Calculated r(C-H) bond lengths and (1)J(C-H) coupling constants for C-H bonds participating in more than one hyperconjugative interaction show additivity of the effects.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.