Enantioselective Template‐Directed [2+2] Photocycloadditions of Isoquinolones: Scope, Mechanism and Synthetic Applications

Abstract

A strategy for the enantioselective [2+2] photocycloaddition of isoquinolones with alkenes is presented, in which the formation of a supramolecular complex between a chiral template and the substrate ensures high enantioface differentiation by shielding one face of the substrate. Fifteen different electron-deficient alkenes and ten different substituted isoquinolones undergo efficient photocycloaddition, yielding the cyclobutane products in excellent yields and with outstanding regio-, diastereo- and enantioselectivities (up to 99% ee). The mechanism of the reaction is investigated by means of triplet sensitization/quenching and radical clock experiments, the results of which are consistent with the involvement of a triplet excited state and a 1,4-biradical intermediate. The variety of functionalized cyclobutanes obtained using this approach can be further increased by straightforward synthetic transformations of the photoadducts, allowing rapid access to libraries of compounds for various applications.

Photochemical [2 + 2] Cycloaddition of Alkenyl Boronic Derivatives: An Entry into 3-Azabicyclo[3.2.0]heptane Scaffold

“… Also, the Lewis acid-catalyzed reaction of allene 7 and pinacol ester 8 resulted in cyclobutyl boronate 9 . An example of the photochemical [2 + 2] cycloaddition of vinyl boronate 1 was described for the case of isoquinolone 10 as the cycloaddition partner: the reaction was performed in the presence of a chiral hydrogen-bonding template 11 and led to cyclobutyl boronate derivative 12 . , …”

“…67 An example of the photochemical [2 + 2] cycloaddition of vinyl boronate 1 was described for the case of isoquinolone 10 as the cycloaddition partner: the reaction was performed in the presence of a chiral hydrogenbonding template 11 and led to cyclobutyl boronate derivative 12. 68,69 In this work, we have envisaged the photochemical [2 + 2] cycloaddition of alkenyl boronic derivatives and maleimides as a general method for the synthesis of borylated 3azabicyclo[3.2.0]heptanes. As this methodology for constructing cyclobutane-derived boronates is very scarcely represented in the literature, a wide range of alkenyl boronic derivatives (including those bearing protected amino, ketone, or carboxylate groups) as well as other reaction partners (maleimides and other electron-poor alkenes) have to be studied in the [2 + 2] cycloaddition to evaluate the scope and limitations of the method, keeping in mind the possibility of the multigram synthesis (Scheme 2).…”

Enantioselective Intermolecular [2 + 2] Photocycloaddition Reactions of 2(1H)-Quinolones Induced by Visible Light Irradiation

“…With this in mind, other substrates which contain a lactam binding motif and which show a high intermolecular reaction rate should be equally suitable for the enantioselectively catalyzed intermolecular [2 + 2] photocycloaddition reaction. A preliminary experiment with parent 1­(2 H )-isoquinolone and methyl vinyl ketone revealed that a high enantioselectivity can be achieved also with isoquinolone substrates (Scheme ). Product 8 was obtained as a single isomer in 91% ee .…”

Advanced Synthesis Using Photocatalysis Involved Dual Catalytic System

“…One reason for this discrepancy may be the unique challenge of controlling crossed vs homodimerization in [2 + 2] cycloadditions, thus leading to difficulties in the preparation of many cyclobutanecontaining natural products and similarly complex bioactive cyclobutane compounds. [90] Yoon et al report a conceptually novel approach for chiral Lewis acid catalyzed crossed [2 + 2] photocycloaddition for the synthesis of a series of vinylcyclobutanes with high enantioselectivity. [91] In 2017, they reported a Sc(OTf) 3 catalyzed chalcones (Scheme 20), [92] which enabled the highly enantioselective crossed [2 + 2] cycloaddition of styrenic olefins and provided a controlled method to directly synthesize 1,2-diarylcyclobutane structures.…”