A 2-Pyridone Photo-[4 + 4] Approach to the Taxanes

Abstract

Pyridones tethered by a four-carbon chain at the 3- and 6’-positions can undergo [4 + 4] photocycloaddition to simultaneously form three, but not four, tetrasubstituted carbons. In a study directed at the taxanes, photocycloaddition of 28 was found to be fully controlled by a (tert-butyldimethylsilyl)oxy group on the tether, to give a photoproduct with five stereogenic centers and both quaternary carbons found in taxol (paclitaxel). This photoproduct proved to be unstable to silica gel, but saturation of one alkene gave a stable product (30). Epoxidation of the enol ether of 30 proceeds exclusively from one face of the cyclooctene ring, demonstrating the facial bias of the polycyclic system and correctly introducing the C-2 stereogenic center of taxol. As part of this study, 4-methoxy-2-pyridones, known to be inert to [4 + 4] photodimerization, were found to undergo [4 + 4] photocycloaddition with 4-unsubstituted-2-pyridones both inter- and intramolecularly.

Photochemical Reactions in Supramolecular Assemblies of Gels: Dimerizations and Polymerizations via Pericyclic Reactions

“…Interestingly, the irradiation of the binary gel matrix of 1 and 2 resulted in the formation of head-to-head (HÀH) photodimers C and D which are minor products by conventional solid state or solution state reactions ( Figure 1). [13][14][15][16][17]34,35] The xerogel of this binary gel was found to be unreactive. Further, the photoirradiation of the binary mixture in THF (non-gelating solvent) was found to reverse the stereochemistry of the products to form A and B (head-to-tail).…”

“…Generally, the [4+4] cyclo‐dimerization of 2 can produce four photoproducts which include anti‐ and syn‐ products of head‐to‐tail (H−T: A and B) and anti‐ and syn‐ head‐to‐head (H−H: C and D) dimerizations. Interestingly, the irradiation of the binary gel matrix of 1 and 2 resulted in the formation of head‐to‐head (H−H) photodimers C and D which are minor products by conventional solid state or solution state reactions (Figure ) ,,. The xerogel of this binary gel was found to be unreactive.…”

“…[1][2][3][4][5][6][7] Despite of surge on the exploration of various aspects of gels, the study on covalent reactions in the gel state is at its infancy although they have parallels with solutions and solids in terms of their properties. In this context, the photochemical addition reactions such as [2 + 2] [8][9][10][11][12] and [4 + 4] [13][14][15][16][17] are well studied in the solid state given the high yield formation of products in regio and stereospecific manner. [8][9][10][11][12][13][14][15][16][17] These reactions are promoted in solid-state given the formation of molecular assemblies which increases the proximity of the reacting functional groups.…”

“…In this context, the photochemical addition reactions such as [2 + 2] [8][9][10][11][12] and [4 + 4] [13][14][15][16][17] are well studied in the solid state given the high yield formation of products in regio and stereospecific manner. [8][9][10][11][12][13][14][15][16][17] These reactions are promoted in solid-state given the formation of molecular assemblies which increases the proximity of the reacting functional groups. Like crystalline solids, the gels are also composed of supramolecular assemblies with partly restricted movements of molecules that can be used for the promotion of photochemical reactions in stereo selective manner.…”

Photocycloaddition in Natural Product Synthesis

“…The Sieburth group have also used 2‐pyridone [4+4] photocycloadditions in an approach to the anticancer natural product taxol (Scheme ) 111–113. Smooth photochemical cyclisation of the bis(2‐pyridone) 165 afforded compound 166 as a single isomer.…”