Iodocyclization of N-Arylpropynamides Mediated by Hypervalent Iodine Reagent: Divergent Synthesis of Iodinated Quinolin-2-ones and Spiro[4,5]trienones

Abstract

PhI(OCOCF) acts as both a nonmetal oxidant and an iodination reagent to trigger iodocyclization of N-arylpropynamides while selectively affording iodinated quinolin-2-ones or the spiro[4,5]trienone skeleton, depending on the substituent pattern. In cases where the N-arylpropynamide bears a para-fluorine on the aniline ring, the spiro compound is formed via an exclusive defluorination process; otherwise, the product was quinolin-2-one.

Role of Lewis‐Base‐Coordinated Halogen(I) Intermediates in Organic Synthesis: The Journey from Unstable Intermediates to Versatile Reagents

“…So far, numerous applications of hypervalent halogens, mostly hypervalent iodine, have been explored. Whereas iodine(III) and iodine(V) have been extensively studied, little is known about halogen(I) intermediates owing to their unstable nature. Moreover, systematic accounts focusing on their reactivity upon interaction with Lewis bases are rare.…”

Unexpected Substituent Effects in Spiro-Compound Formation: Steering N-Aryl Propynamides and DMSO toward Site-Specific Sulfination in Quinolin-2-ones or Spiro[4,5]trienones

“…With regard to the spirolization of the F-substituted substrates, we and others postulated a concerted pathway containing simultaneous nucleophilic attack and spiro-formation processes ( Scheme 2 ). 10c , 23 As this overall pathway would depend on significant positive charge development on the F-bound ipso -carbon atom to make attack by, e.g., methanol ( Scheme 2 a) or triflate attractive ( Scheme 2 b), and also would require a large reduction of entropy in the transition state to allow for the synchronous intermolecular nucleophilic attack and the intramolecular ring closure, we wondered whether a conceptually simpler alternative might be found.…”

“…Such low barrier implies that, in contrast to earlier suggestions, no nucleophilic assistance is needed or even likely for spiro-formation. 10c , 23 While F is generally thought of as an electron-withdrawing substituent (e.g., σ m and σ p values of 0.34 and 0.06, respectively), 29 when bound directly to a (partially) positive carbon atom [C + –F or C δ+ –F] it is actually frequently stabilizing due to resonance effects, 30 in line with the stabilization observed here compared to R = H. For R = OMe intermediate B is a verified minimum (no imaginary vibrational frequencies), but no proper transition state could be located, and a relaxed potential energy scan suggests <0.5 kcal/mol as activation barrier.…”

Convenient Synthesis of 6,7,12,13-Tetrahydro-5H-Cyclohepta[2,1-b:3,4-b’]diindole Derivatives Mediated by Hypervalent Iodine (III) Reagent

“…Intermolecular oxidative coupling reactions of aromatic rings mediated by hypervalent iodine reagents have been studied by many researchers and many excellent examples have been reported, including heteroaromatic couplings [29,30,31,32,33,34], cross-couplings of heteroaromatic and aromatic rings [35,36,37] and aromatic couplings [38,39,40,41]. In the meantime, some progress have been achieved in intramolecular oxidative coupling reactions mediated by hypervalent iodine reagents, including the establishment of spiro structures [42,43,44] and fused rings [45,46,47,48]. Constructing a seven-membered ring through intramolecular oxidation is still highly desirable.…”