We report the first example of a traceless directing group in a radical cascade. The chemo- and regioselectivity of the initial attack in skipped oligoalkynes is controlled by propargyl OR moiety. Radical translocations lead to the boomerang return of the radical center to the site of initial attack where it assists the elimination of the directing functionality via β-scission in the last step of the cascade. The Bu3Sn moiety continues further via facile reactions with electrophiles as well as Stille and Suzuki cross-coupling reactions. This selective radical transformation opens a new approach for the controlled transformation of skipped oligoalkynes into polycyclic ribbons of tunable dimensions.
N-oxyphthalimides are stable and easily accessible compounds that can produce oxygen radicals upon 1-electron reduction. We present a systematic study of electrochemical properties of N-oxyphthalimide derivatives (PI-ORs) in DMF by cyclic voltammetry. In all cases, electron transfer to the substrate leads to decomposition of the intermediate radical anion via the N-O bond cleavage. In the case of benzyloxyphthalimide or its derivatives containing electrondonating substituents, reductive electron transfer induces the chain decomposition of the substrate to phthalimide (PI) radical-anion and the corresponding carbonyl compound. The PI radical-anion product is a powerful reductant that can transfer an electron to the reactant PI-OR, thus establishing a catalytic cycle for reductive N-O scission. This self-catalytic process is reflected in a considerable decrease in the reduction current for the substrate (<1e -/molecule). By contrast, reductive fragmentations of benzyl derivatives containing electronwithdrawing substituents in the aromatic ring or at the benzylic position, as well as tosyl and alkyl derivatives, occur via a 1-electron mechanism. A sequence of N-O and C-C scissions was engineered to support the intermediacy of O-centered radicals in these processes.
Radical cyclization reactions at a peri position were used for the synthesis of polyaromatic compounds. Depending on the choice of reaction conditions and substrate, this flexible approach led to Bu Sn-substituted phenalene, benzanthrene, and olympicene derivatives. Subsequent reactions with electrophiles provided synthetic access to previously inaccessible functionalized polyaromatic compounds.
Cascade radical transformations of acyclic precursors open efficient, convenient and atom-economical access to functionalized compounds of increased structural complexity. This report describes a selective sequence of 5-exo-dig and 6-exo-dig cyclizations followed by attack at a pendant aromatic moiety and rearomatization.
Computational
analysis quantifies key trends in “peri”-radical
cyclizations, a recently developed
type of ring-forming reaction for the expansion of polyaromatic systems
at the zigzag edge. Comparison of vinyl radical attack on the peri-position versus a topologically similar six-membered
ring formation at the armchair edge reveals that the barriers for
the peri-ring closure are slightly higher, even though
the peri-attack is more exergonic. On the other hand,
the intramolecular competition between the formation
of a five-membered ring by ortho-attack at the armchair
edge and formation of a six-membered ring by peri-attack at the zigzag edge clearly favors six-membered ring formation.
The key novel finding is the unprecedented sensitivity of peri-cyclization to the presence and spatial orientation
of a “spectator” propargylic −OMe substituent.
Remarkably, formation of cis-products proceeds, in
general, through a significantly (∼2–4 kcal/mol) lower
barrier than formation of the trans-products, even
when the cis-products are less stable. The origin
of this unexpected effect is clearly stereoelectronic. These findings
identify such remote substitution as a conceptually new tool for the
control of rate and selectivity of radical reactions. The correlations
of activation barriers for vinyl radical attack with aromaticity of
the target show the expected relationship in phenanthrenes and pyrenes
but not in anthracenes. In the latter case, the attack at the less
aromatic ring corresponds to a higher barrier because a steric penalty
on the stereoelectronically favorable cis-TS negates
the accelerating influence of the properly aligned C–O and
C–Sn bonds.
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