High-Pressure-Promoted and Facially Selective Diels–Alder Reactions of Enzymatically Derived cis-1,2-Dihydrocatechols and Their Acetonide Derivatives: Enantiodivergent Routes to Homochiral and Polyfunctionalized Bicyclo[2.2.2]octenes

Abstract

cis-1,2-Dihydrocatechols 5 (X= Me and Cl), which are available in homochiral form through the whole-cell biotransformation of toluene and chlorobenzene, respectively, undergo Diels-Alder cycloaddition reactions with a range of electron-deficient dienophiles at 19 kbar (1.9 GPa). The favored products of such reactions are adducts of the general form 8 and that arise through the operation of a contrasteric or syn-addition pathway. In contrast, the acetonide derivatives of metabolites 5 undergo anti-selective addition reactions under the same conditions and so producing adducts of the general form 10. Bicyclo[2.2.2]octenes 8 and 10, which embody carbocyclic frameworks of opposite enantiomeric form, are useful scaffolds for chemical synthesis.Computational studies reveal that syn-adduct formation is kinetically and normally thermodynamically favored over anti-adduct formation when the free diols 5 are involved but the reverse is so when the corresponding acetonides participate as the 4π-addend. Furthermore, the reactions become more exothermic as pressure increases while, concurrently, the activation barrier diminishes and at 6 GPa (60 kbar) almost vanishes.

Hyperbaric reactions in organic synthesis. Progress from 2006 to 2021

“…Diels–Alder reactions of cis -1,2-dihydrocatechols 78 with monosubstituted EWG-activated alkenes 77 are found to show facial-selectivity, depending on the nature of the OR 2 substituent, and require 19 kbar of pressure for activation (Scheme 24). 69 Thus, anti -adducts 80 can be obtained in the case when R 2 + R 2 is CMe 2 , and syn -products 79 can be synthesized from unprotected (R 2 = H) dihydrocatechol 78 with yields up to 86%. Access to enantiopure partially hydrogenated catechols is the advantage of the enzymatic enantioselective dihydroxylation reaction, 70 where bacterial dioxygenases (for example, the blocked mutant strain Pseudomonas putida 39/D, which can be grown under laboratory conditions) play the role of promoters.…”

Regioselectivity Switch Towards the Development of Innovative Diels‐Alder Cycloaddition and Productive Applications in Organic Synthesis

“…The majority of Diels‐Alder cycloadditions are governed by π ‐facially selectivity, provided the diene is appropriately substituted considering electronic and structural rearrangement [152,153] . According to the Martin G. Banwell's group in 2020, the π ‐facially selectivity of certain allylic and heteroatom‐based substituents linked with the participating diene, facilitates the π ‐selective addition of dienophile preferentially [154] . Moreover, high pressure driven and facially selective Diels‐Alder cycloaddition of enzymatically derived cis ‐1,2‐dihydrocatechols and their acetonide derivatives was critically studied.…”

“…Moreover, high pressure driven and facially selective Diels‐Alder cycloaddition of enzymatically derived cis ‐1,2‐dihydrocatechols and their acetonide derivatives was critically studied. The proposed methodology also represents one of the accomplishments in the field of enantio‐divergent routes to homo‐chiral and polyfunctionalized bicycle[2.2.2]octenes, which subsequently focuses on achieving a high degree of selectivity [154] . Interestingly, treatment of dihydro‐catechols 125 (essentially available in homochiral form through whole‐cell biotransformation of toluene and chlorobenzene respectively) with a range of electron‐deficient dienophiles 126 under Diels‐Alder cycloaddition pathway at 19kbar preferred adduct 127 via syn ‐selective cycloaddition.…”

High-pressure reaction profiles and activation volumes of 1,3-cyclohexadiene dimerizations computed by the extreme pressure-polarizable continuum model (XP-PCM)

“…The XP-PCM method has been applied to the calculations of the energy profiles of a subset of pericyclic reactions. 17,31 Interesting phenomena such as a shift of the transition state and a switch of the rate determining step have been discovered by the calculations. 17 Furthermore, the computed ∆ ‡ are in reasonable agreement with experimental value.…”