Chemistry of Acyl Radicals

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

The oxidation of alcohols into aldehydes and ketones can be efficiently performed using catalytic amounts of CuCl . Phen and molecular oxygen or air. This novel, ecologically friendly procedure releases water as the only byproduct.

Efficient, ecologically benign, aerobic oxidation of alcohols

The formation of a new σ-bond at the expense of an existing π-bond is a transformation that rests at the heart of modern organic synthesis It underlies such diverse reactions as nucleophilic additions to carbonyls and activated alkenes, transition metal catalyzed additions, and pericyclic reactions The addition of a radical to a π-bond, to form a σ-bond and a new radical, is a fundamental reaction of organic radicals that organic polymer chemists have continuously applied to the synthesis of new materials Applications in small molecule synthesis evolved more slowly for a time1,2 However, over the last decade, the application of radical addition reactions to problems in fine synthesis has grown from the level of a curiosity to that of a major reaction class For recent reviews see refs 3–5 This rapid growth can be attributed, in part, to the high level of understanding of organic radicals that has been provided by fundamental research on structure and reactivity and, in part, to the fact that the transformations that can be accomplished by radical additions are often those that are difficult to accomplish by more traditional means

4.1 – Radical Addition Reactions

Polar substituents are gen'erally more efficient for the stabil.isation of ions than for radicals. These last species are more and more recognised as inmortant intermediates in chemistry and in biochemistry. The cumulative effect of two substituents of the same polarity shows antagonism for radical. stabilisation whereas captodative (cd) substituents show synergy. Synthetic applications of the cd-effect use the breaking of adjacent weak \"proradical\" C-H and C-C bonds. Further, cd-double bonds are useful as radical traps and as partners in cycloaddition reactions. cd-N-vinyl. substitution induces with complete stereocontrol. the epoxy-epimination rearrangement of chiral oxazines and opens a new route to inosite and streptamine derivatives. 1636 H. G. VIEHE, R. MERENYI AND 2. JANOUSEK OM(/CN CM/OMe SR /CN NH7/CN COOEt/NISir* 3) COOEt/OH SMe /COO Et OMe/COOEt cd-Dichloromethylene compounds with aminosubstituents as dative group have l.ittle ionic character but do display it in substitution reactions with nucleophiles if the rearrangement is avoided, for example, by temperature control. With the CF3-group as captor group potential. a-trifluoromethyl-cations are available both before and after the rearrangement which takes place around 1.OO0C (ref. 6) (Fig. 3). + 1.0 + 5.17 + 16.0 + 6.91 0.3 + 13.0 + L.2 + 9.6 + 12.8 1 7.6 + 2.6 + 0.8 re f 8 ' O o'*I 9 I % Fig. 3 C H3C I

Captodative Substituent Effect .45. Captodative Substituent Effects in Radical Chemistry

Capto-dative Substituent Effects .8. Bridged Dehydrodimerization As a General-method of Synthesis - C-4-bridging With Alpha-tert-butylmer-captoacrylonitrile

H.G. Viehe

Papers

Captodative Substituent Effect .45. Captodative Substituent Effects in Radical Chemistry

Capto-dative Substituent Effects .8. Bridged Dehydrodimerization As a General-method of Synthesis - C-4-bridging With Alpha-tert-butylmer-captoacrylonitrile

Capto-dative Substituent Effects .13. C-4-bridged Radical Dimerization With Alpha-phenylselenoacrylic Acid-derivatives

Captodative Substituent Effects .15. Generalization of Bridged Dehydrodimerisation By Varying Radicophiles and Polarity of Attacking Radicals

Captodative substituent effects XXI.