Fluorine Effects for Tunable C–C and C–S Bond Cleavage in Fluoro-Julia–Kocienski Intermediates

Abstract

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Secondary Orbital Effect Involving Fluorine is Responsible for Substrate‐Controlled Diastereodivergence in the Catalyzed syn‐aza‐Henry Reaction of α‐Fluoronitroalkanes

“…It is complementary, however, to the rationale for α-fluorosulfone behavior for which a p(F)!π*(Ar) was identified as the responsible secondary orbital interaction. [32] The enantiomeric transition state structure (F)-anti-(1S,2S)-TS2 (ΔG � = 14.9 kcal/mol), with a CÀ C bond-forming distance of 2.12 Å, was the next lowest-in-energy structure, still 4.8 kcal/ mol higher relative to structure (F)-anti-(1R,2R)-TS2. Examination of this transition state structure revealed a single, favorable π-π stacking interaction between the substrates, as well as a constrained tert-butyl group that is wedged between the quinoline rings of the BAM catalyst.…”

“…Notably, this computational finding is in line with our initial hypothesis, [10] in which the aryl groups are pivotal in directing nitronate addition to the aldimine, ultimately leading to anti ‐selectivity, despite the presence of fluorine. It is complementary, however, to the rationale for α‐fluorosulfone behavior for which a p(F)→π*(Ar) was identified as the responsible secondary orbital interaction [32] …”

Theoretical Study on the Origin of Abnormal Regioselectivity in Ring-Opening Reaction of Hexafluoropropylene Oxide

“…Our results provide strong support for Jiang’s [ 20 ] and Lemal’s [ 23 ] hypotheses. We expected that the insights from this study would enrich our understanding of unique fluorine effects in organic reactions [ 25 , 74 , 75 , 76 , 77 , 78 ] and should be helpful for the design of new regioselective ring-opening reactions of epoxides by regulating the electronic properties of the substituents.…”

High Chemo-/Stereoselectivity for Synthesis of Polysubstituted Monofluorinated Pyrimidyl Enol Ether Derivatives

“…First, they have great tolerance of powerful anionic chemistry (α-alkylation and fluorination) for functional elaboration before the nucleophilic addition event; and their stability and crystallinity allow for convenient manipulation. Therefore, the literature is replete with examples of a variety of different roles in synthesis from J–K olefination, − Micheal addition, and nucleophilic fluoroalkylation to their use in synthesis of monofluoroalkenyl sulfone (Scheme A). Compared with these transformations which (α-fluoro-β-keto-sulfones) react as carbon nucleophile reagents, herein, we first show that readily available α-fluoro-β-keto-2-pyrimidinylsulfone 1 can be directly used as an oxygen nucleophile reagent for intramolecular Smiles rearrangement to synthesize monofluorinated pyrimidyl enol ethers 2 (Scheme B).…”