Visible Light-Induced Regio- and Enantiodifferentiating [2 + 2] Photocycloaddition of 1,4-Naphthoquinones Mediated by Oppositely Coordinating 1,3,2-Oxazaborolidine Chiral Lewis Acid

Abstract

A range of asymmetric photochemical transformations using visible light have recently become considerably attractive. Among the various approaches, chiral Lewis acid association to enones for [2 + 2] and ortho photocycloadditions and oxadi-π-methane rearrangements have shown to be very promising. Naturally, chiral Lewis acid coordination protects one of the prochiral faces of the CC double bond, which enables an effective enantiodifferentiation in the following bond-forming process(es). Here, we studied regio-and enantiodifferentiating [2 + 2] photocycloaddition reactions of naphthoquinone derivatives mediated by chiral oxazaborolidines. A stereochemical control was quite challenging for the 2-ene-1,4-dione substrate, as a double coordination of Lewis acid essentially cancels out the face selectivity, and a mono-coordination to each carbonyl group leads to an opposite stereochemical outcome. Furthermore, a stepwise coordination in the ground state of Lewis acid in a 1:1 fashion was practically inaccessible. We found that the excited-state decomplexation is a key to accomplish high regio-and enantioselectivities in the photocycloaddition of an ene-dione.

The Role of N-Substitution in Regio- and Stereoselective Vinylogous Imidonaphthoquinone (VINAquinone) [2 + 2] Photocycloadditions

“…That the enantioselective [2 + 2] cycloaddition of 4 using chiral Lewis acids is complicated by the propensity of the Lewis acids to coordinate to both naphthoquinone carbonyl groups makes the results with 28 all the more impactful. 14 We were able to obtain a single-crystal X-ray structure of 31 (see Figure 2). The X-ray structure not only confirmed our structural assignment, but it also hinted at a reason for the reaction's diastereoselectivity.…”

“…These results clearly demonstrate that it is possible to flip the inherent tendency for crossed products in 2° VINAquinone cycloadditions with relatively simple modifications on the N -atom and that the absolute stereochemistry of the products can also be controlled. That the enantioselective [2 + 2] cycloaddition of 4 using chiral Lewis acids is complicated by the propensity of the Lewis acids to coordinate to both naphthoquinone carbonyl groups makes the results with 28 all the more impactful …”

“…Although cyclobutane formation and fragmentation sequences have been employed previously, we were unaware of their use to generate spiro-fused quinones or naphthoquinones. , In addition to this, only a few examples of intramolecular [2 + 2] photocycloadditions of naphthoquinones have been reported. , The most relevant of these to our proposed sequence was communicated by Mori, Bach, and co-workers in 2022. , They described the intramolecular photocycloadditions of naphthoquinones 4 – 6 having a three-carbon tether between a terminal alkene and the naphthoquinone (Scheme ). Interestingly, while the reaction of 4 gave 7 as the major product, it also gave a small amount of crossed-cycloadduct 10 .…”

“…12,13 The most relevant of these to our proposed sequence was communicated by Mori, Bach, and co-workers in 2022. 14,15…”

Enantiodivergent Photochemical Rearrangements Due to Different Coordination Modes at an Oxazaborolidine Lewis Acid Catalyst

“…In recent years, AlBr 3 -activated oxazaborolidines have been shown to be particularly suited to catalyze photochemical transformations yielding synthetically useful building blocks in high enantiomeric excess . Most notably, they enabled a broad variety of enantioselective [2 + 2] photocycloaddition reactions, both intra- and intermolecularly . An early example relates to the intramolecular [2 + 2] photocycloaddition of 5,6-dihydro-4-pyridone 1 to cyclobutane 2 (Figure B). , Typically, the photochemical reactions proceed via the reversible binding of Lewis acid 3 to the carbonyl oxygen atom, which induces a bathochromic shift and allows for selective excitation of the substrate–catalyst complex.…”