Asymmetric Photocycloaddition in Solution of a Chiral Crystallized Naphthamide

Abstract

Asymmetric synthesis starting from an achiral material and in the absence of any external chiral agent has long been an intriguing challenge to chemists [1] and is also central to the origin of optical activity in Nature.[2] Stereospecific solid-state chemical reactions of chiral crystals formed by spontaneous crystallization of achiral materials are defined as "absolute" asymmetric synthesis, and most of the successful examples of such transformations involve photochemical reactions. [1,3] If the molecular chirality generated by chiral crystallization is retained even after the crystals are dissolved in a solvent, the "frozen" chirality is effectively transferred to the optically active products by various types of asymmetric reactions, besides the solid-state photochemical reaction. [4,5] Herein, we provide the first example of an asymmetric intermolecular photochemical reaction in solution through transfer of the chirality generated by chiral crystallization of an achiral naphthamide.2-Alkoxy-1-naphthamides 1 were chosen to perform this asymmetric synthesis because the bond rotation between the naphthalene ring and the C=O(NR 1 R 2 ) group corresponds to enantiomerization of 1, and the rate is considerably affected by the substituents on both the naphthalene ring and the amide group (Scheme 1).[6] Naphthamides comprising a bulky Scheme 1. Enantiomerization of naphthamides 1 a, b upon rotation about the naphthalene-C( = O) bond.

Practical Role of Racemization Rates in Deracemization Kinetics and Process Productivities

“…These observations are ascribable to hydrogen bonding between the carbonyl oxygen of 1 and the solvent, which reduces the rate of racemization. Although Sakamoto et al reported that 1 retains its chirality in MeOH through hydrogen-bonding interactions, 32 our systematic study reveals that 1 racemizes at a rate depending on the solvent polarity; this trend is particularly conspicuous within the same solvent series.…”

“…The crystal form obtained by deracemization was the same as that reported earlier. 32 The evolution of enantiomeric excess was sigmoidal in nature. This behaviour is often observed in solid-state deracemizations.…”

“…Indeed, compound 1 exhibits frozen atropisomerism in its solid state, whereas it spontaneously racemizes in solution. Naphthamide 1 has previously been reported by Sakamoto et al, 32 and our sample was synthesized using a similar route (Scheme 1), the details of which can be found in the Supporting Information. Large single crystals (5−30 mg) for racemization-rate experiments were also prepared by the slow evaporation of a saturated 1:1 (v/v) CHCl 3 /heptane solution.…”

Supramolecular Photochemistry as a Potential Synthetic Tool: Photocycloaddition

“…166,319,320 A variation of this has been used to perform chiral photochemistry in solution. 321 Spontaneous crystallization of achiral naphthamide 54 322 that crystallized in a chiral space group P2 1 2 1 2 1 has been exploited for an asymmetric photoreaction in a solution media (Scheme 37).…”

“…The frozen chirality approach 322,324,325 was also utilized for the intermolecular [2 + 2] photocycloaddition of N,N-diethyl-4coumarin-3-carboxamide 58 (that crystallized in P2 1 2 1 2 1 chiral space group) with vinylethers 59 (Scheme 39). 325 Due to the slow hindered C(CO) bond rotation carboxamides exist in enantiomeric form in solution, while they were present in a single enantiomeric form in the crystalline state (depending on which enantiomer was used as the seed or spontaneously crystallized).…”