Selective Intermolecular Photo-[4 + 4]-cycloaddition with 2-Pyridone Mixtures. 3. Synthetic Transformations of the Trans Cross-Product (1α,2β,5β,6α)-3-Butyl-9- methoxy-3,7-diazatricyclo[4.2.2.2^2,5]dodeca-9,11-diene-4,8-dione

Transformations of the tricyclic product 3 derived from [4 + 4] photocycloaddition of N-butyl-2-pyridone with 4-methoxy-2-pyridone has demonstrated, for the first time, facile opening of the secondary lactam after activation of the amide nitrogen with a tert-butyl carboxylate (Boc) group. Methanolysis and lithium borohydride reduction both result in opening of the amide group under very mild conditions to give 21 and 24, respectively. Concomitant reduction of a ketone derived from hydrolysis of the enol ether sets an additional stereogenic center in 24 with complete stereogenic control. These reactions illustrate the synthetic potential of the 2-pyridone photocycloaddition products, generating a cyclooctene as a single isomer, with functionality at seven carbons and five stereogenic centers

Selective Intermolecular Photo-[4 + 4]-cycloaddition with 2-Pyridone Mixtures. 2. Preparation of (1α,2β,5β,6α)-3-Butyl- 9-methoxy-3,7-diazatricyclo[4.2.2.2^2,5]dodeca-9,11-diene-4,8-dione

Photochemistry of 2-pyridone mixtures can be selective and thereby lead to useful quantities of [4 + 4] cycloaddition cross products. The selective intermolecular reaction described here employs an excess of 4-methoxy-2-pyridone (6), which does not photodimerize but will undergo [4 + 4] cycloaddition with 2-pyridones without a 4-methoxy group such as N-butyl-2-pyridone 12. Isolated yields of the trans product (1α,2β,5β,6α)-3-butyl-9-methoxy-3,7-diazatricyclo[4.2.2.22,5]dodeca-9,11-diene-4,8-dione (7) are very sensitive to the ratio of the two starting pyridones, and this product has been isolated in yields of up to 51%. This photoreaction produces, in a single step from simple aromatic precursors, a tricyclic product with four stereogenic centers and four distinct functional groups

A [4 + 4] 2-Pyridone Approach to Taxol. 3. Stereocontrol during Elaboration of the Cyclooctane

Intramolecular photocycloaddition of 2-pyridones connected through a four-carbon tether (6-[4-(1,2-dihydro-1-methyl-2-oxo-3-pyridinyl)-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]butyl]-4-methoxy-1,3-dimethyl-2(1H)-pyridinone) yields a single tetracyclic product with four new stereogenic centers. The diastereoselectivity of this [4 + 4] reaction is fully controlled by a stereogenic carbon of the tether. Treatment of the photoproduct with osmium tetraoxide transforms the alkene to a diol and the enol ether to an α-hydroxy ketone, with stereocontrol dictated by nearby lactams that block one face of each alkene. Allylmagnesium bromide addition to the ketone also yields a single diastereomer, but unexpectedly this product results from approach of the nucleophile to the most-hindered face of the ketone. Study of this reaction in a model system has found the allylic nucleophile to be unique, with nonallylic reagents approaching along the expected, least-hindered path. This contrasteric addition likely results from coordination of the allylic nucleophile to the nearby amide. The amide can therefore act either as a steric shield or as a directing group. The three steps of photocycloaddition, cis-hydroxylation, and nucleophilic addition constructs both quaternary carbons of the cyclooctane and four of the five stereogenic centers found in the eight-membered ring of Taxol

Polyquinanes by [4 + 4] Cycloaddition−Transannular Cyclization

Photocycloaddition of 2-pyridones yields a rigid polycyclic product containing a 1,5-cyclooctadiene. The cis isomer, with the alkenes in close proximity, undergoes a transannular reaction when treated with chlorine to give a polyquinane product. The chlorination reaction involves migration of an amide nitrogen and forms a single isomer, generating eight stereogenic centers in two steps