Using Ring Strain to Control 4π-Electrocyclization Reactions: Torquoselectivity in Ring Closing of Medium-Ring Dienes and Ring Opening of Bicyclic Cyclobutenes

Abstract

Syntheses of strained cyclic dienes were accomplished via palladium(II)-catalyzed oxidative cyclizations of terminal bis(vinylboronate esters). The reactions generate strained (E,E)-1,3-dienes that undergo spontaneous 4π-electrocyclizations to form bicyclic cyclobutenes. Formation of the cyclobutenes is driven by the strain in the medium-ring (E,E)-1,3-diene intermediate. Thermal ring openings of the cyclobutenes give (Z,Z)-1,3-diene products, again for thermodynamic reasons. DFT calculations verified the thermodynamic versus kinetic control of the reactions, and kinetic studies are in excellent agreement with the calculated energy changes. An extension of the tandem coupling/4π-electrocyclization pathway was demonstrated by a palladium(II)-catalyzed oxidative homocoupling/8π-electrocyclization cascade.

A vector‐based representation of the chemical bond for predicting competitive and noncompetitive torquoselectivity of thermal ring‐opening reactions

“…In reactions that lack a high degree of symmetry where electrostatic, steric, and directional effects are important the traditional symmetry dependent formalism based on the Woodward–Hoffmann rules is insufficient Examples of such reactions include electrocyclic ring‐opening reactions where directional effects in the form of torquoselectivity are present. Torquoselectivity is defined to be the preference for either the transition state (TS) inward conrotatory reaction pathway (TSIC) or the transition state outward conrotatory (TSOC) reaction pathway .…”

A Domino 10-Step Total Synthesis of FR252921 and Its Analogues, Complex Macrocyclic Immunosuppressants

“…This posed a serious threat to our synthetic approach, since only a cis -arrangement of the substituents around the cyclobutene moiety of cis - 31a would result in the desired ( E,E,E )-triene geometric isomer upon domino stereoinvertive Suzuki-type coupling and conrotatory torquoselective 4π-electrocyclic ring-opening. 20 Control experiments revealed that, once the cis -chlorocyclobutene ester cis - 31a was formed, it was kinetically stable under the reaction conditions (see Figure S9). After extensive optimization, we found that the combination of Ghosez’s reagent 21 and pyridine selectively gave the desired cis -chlorocyclobutene ester cis - 31 in 79% yield and a reproducible cis / trans ratio of 8.8:1 (Figure 2C).…”

Questions in natural products synthesis research that can (and cannot) be answered using computational chemistry

“…For example, the energy change ( ∆H , ∆G , pick your poison) for the hypothetical equilibrium shown in Figure 2 could be used to compare (in effect, define) the thermodynamic stability of the two dienes shown or, in other words, to quantify the strain (a common form of stability of interest to organic chemists) for the diene at the far left associated with embedding it within an 11-membered ring. 10 There is a whole hierarchy of types of isodesmic equation that differ in their expected accuracy and ease of interpretation. 11…”