Maltol- and Allomaltol-Derived Oxidopyrylium Ylides: Methyl Substitution Pattern Kinetically Influences [5 + 3] Dimerization versus [5 + 2] Cycloaddition Reactions

• Published in: Journal of organic chemistry 2019-11, Vol.84 (22), p.14670-14678
• Main Authors: Bejcek, Lauren P, Garimallaprabhakaran, Aswin K, Suyabatmaz, Duygu M, Greer, Alexander, Hersh, William H, Greer, Edyta M, Murelli, Ryan P
• Format: Article
• Language: English
• Subjects: Bridged Bicyclo Compounds - chemical synthesis; Bridged Bicyclo Compounds - chemistry; Cycloaddition Reaction; Dimerization; Kinetics; Molecular Structure; Pyrones - chemistry; Tropolone - chemical synthesis; Tropolone - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b02137

Oxidopyrylium ylides are useful intermediates in synthetic organic chemistry because of their capability of forming structurally complex cycloadducts. They can also self-dimerize via [5 + 3] cycloaddition, which is an oft-reported side reaction that can negatively impact [5 + 2] cycloadduct yields and efficiency. In select instances, these dimers can be synthesized and used as the source of oxidopyrylium ylide, although the generality of this process remains unclear. Thus, how the substitution pattern governs both dimerization and cycloaddition reactions is of fundamental interest to probe factors to regulate them. The following manuscript details our findings that maltol-derived oxidopyrylium ylides (i.e., with ortho methyl substitution relative to oxide) can be trapped prior to dimerization more efficiently than the regioisomeric allomaltol-derived ylide (i.e., with a para methyl substitution relative to oxide). Density functional theory studies provide evidence in support of a sterically (kinetically) controlled mechanism, whereby gauche interactions between appendages of the approaching maltol-derived ylides are privileged by higher barriers for dimerization and thus are readily intercepted by dipolarophiles via [5 + 2] cycloadditions.