The past decade of organic chemistry may be charcterized as a period of violent development of new synthetic methods. This was accompained by a systematization of the analysis of synthetic problems (synthetic strategy). The planning of the synthesis of an organic target molecule is greatly facilitated by distinguishing between reagents X(C)n … with normal reactivity (acceptor properties at C1,3,5…, donor properties at X, C2,4…) and with reactivity umpolung (acceptor properties at X, C2,4…, donor properties at C1,3,5…). In this context, reactivity umpolung turned out to be useful as a heuristic principle, as a classification scheme, and as an aid for locating so-called strategic bonds (synthon, transform, and antithesis according to E. J. Corey). There are six principal methods of umpolung: 1 2n-oxidation, heteroatom exchange and modification, homologation and its reversal, the cyclopropane “trick”, use of acetylenes, and redox reactions; under certain circumstances none of these techniques is necessary in cases where direct umpolung is possible. Throughout the article, normal reactivity is indicated by green print; reactivity umpolung by red print.

Methods of Reactivity Umpolung

The electrophilic/nucleophilic character of a series of captodative (CD) ethylenes involved in polar cycloaddition reactions has been studied using DFT methods at the B3LYP/6-31G(d) level of theory. The transition state structures for the electrophilic/nucleophilic interactions of two CD ethylenes toward a nucleophilically activated ethylene, 2-methylene-1,3-dioxolane, and an electrophilically activated ethylene, 1,1-dicyanoethyelene, have been studied, and their electronic structures have been characterized using both NBO and ELF methods. Analysis of the reactivity indexes of the CD ethylenes explains the reactivity of these species. While the electrophilicity of the molecules accounts for the reactivity toward nucleophiles, it is shown that a simple index chosen for the nucleophilicity, Ν, based on the HOMO energy is useful explaining the reactivity of these CD ethylenes toward electrophiles.

Understanding the reactivity of captodative ethylenes in polar cycloaddition reactions. A theoretical study.

Carbon trifluoromethylation reactions of hydrocarbon derivatives and heteroarenes.

There are many reactions in which CC bonds are formed by addition of free radicals to alkenes. Information about the mechanism is important for the synthesis of specific target molecules. The rate of addition of alkyl radicals to alkenes is controlled by steric and polar effects. The stabilities of the educts and products are of only limited importance, since the transition states for these exothermic reactions occur very early on the reaction coordinate. Variations in reactivity and selectivity can be described using frontier orbital theory: for nucleophilic radicals the dominant interactions are those between SOMO's and LUMO's, and for electrophilic radicals those between SOMO's and HOMO's. The large differences in the steric effects of α - and β- substituents of alkenes can be explained by postulating an unsymmetrical transition state— the radical approaches one of the C atoms preferentially. Regioand stereoselectivities can be predicted and are determined, in general, by steric effects.

Formation of CC Bonds by Addition of Free Radicals to Alkenes

The asymmetric α-addition of relatively nonpolar hydrocarbon substrates, such as allyl and aryl groups, to aldehydes and ketones remains a largely unsolved problem in organic synthesis, despite the wide potential utility of direct routes to such products. We reasoned that well-established chiral amine catalysis, which activates aldehydes toward electrophile addition by enamine formation, could be expanded to this important reaction class by applying a single-electron oxidant to create a transient radical species from the enamine. We demonstrated the concept of singly occupied molecular orbital (SOMO) activation with a highly selective α-allylation of aldehydes, and we here present preliminary results for enantioselective heteroarylations and cyclization/halogenation cascades.

http://science.sciencemag.org/content/sci/316/5824/582.full.pdf

Enantioselective Organocatalysis Using SOMO Activation

The captodative effect

Capto‐dative Substituent Effects in Syntheses with Radicals and Radicophiles [New synthetic methods (32)]

Die 100 Jahre alten Wursterschen Salze sind seit langem als Verbindungen mit Radikalkationen erkannt worden. Ihre ungewohnliche Stabilitat beruht teilweise auf capto-dativer (cd) Substitution. Dieses Prinzip wird nun als Faktor der Radikalstabilisierung diskutiert und auf Methinderivate angewendet. cd-Substitution ist fur Synthesezwecke nutzlich: cd-Substituenten am gleichen Kohlenstoffatom ermoglichen selektive Dehydrodimerisierung; Olefine mit geminalen und daher kreuzkonjugierten cd-Substituenten sind „radikophil” und konnen zwei Kohlenstoffradikale addieren; cd-substituierte Olefine sind wirksame Antioxidantien, Polymerisationsinhibitoren und vielversprechende Agentien fur die Kontrolle biologischer Radikalreaktionen. Ganz allgemein konnten viele Reaktionen cd-substituierter Molekule uber Radikale verlaufen.

Capto‐dative Substituenteneffekte bei der Synthese mit Radikalen und Radikophilen

/pdf/substituent-effects-in-radical-chemistry-wfudo1a63v.pdf

Robert Merényi

Papers

The captodative effect

Capto‐dative Substituent Effects in Syntheses with Radicals and Radicophiles [New synthetic methods (32)]

Capto‐dative Substituenteneffekte bei der Synthese mit Radikalen und Radikophilen

Substituent Effects in Radical Chemistry

Stabilization of Radicals by “Capto‐Dative” Substitution ? C ? C Addition to Radicophilic Olefins