Formation and isomerization of polycyclic 1,5-enynes

Abstract

a b s t r a c t A 1,5-enyne with the alkyne flanked by a cyclopropane and a cyclobutane, formed by intramolecular [2+2] photocycloaddition of a pyridone with an enyne, undergoes gold catalyzed ring closure to give a cyclopentene, without isomerization of either small ring. The ring closure can also be effected by thiol radical conditions. The chemistry of the resulting tetracycle with its five stereogenic centers, has been studied.Ó 2015 Elsevier Ltd. All rights reserved.Assembly of polycyclic molecules with useful complexity from simple reagents is a gold standard in organic synthesis. 2 During our investigations of 2-pyridone photochemistry we have studied its cycloaddition with 1,3-enynes and discovered two different pathways based on the presentation of the enyne. 3,4 When the enyne is attached through the alkyne (1), only [4+4] cyclization results and the highly strained allene product 2 is, in most cases, unstable and undergoes further reaction. In contrast, when the enyne is linked to the pyridone through the alkene (3), only [2+2] products are observed (see Scheme 1). The stereochemically rich cyclobutane 4 presented opportunities to study the reactivity of this strained and densely functionalized structure, particularly its cis-1,5-enyne. We report herein our investigation of the formation and reactivity of 4 and related structures.The formation of [2+2] adduct 4 is notable for several reasons. In addition to creating two adjacent quaternary carbons, the cycloaddition occurs with retention of the alkene stereochemistry, whereas [2+2] cycloaddition of enones with alkenes is typically accompanied by scrambling of the alkene stereochemistry. 5 Enone photochemistry is largely triplet-derived and bond formation in enone [2+2] cycloadditions are often stepwise and reversible, leading to the stereochemical isomerization. In contrast, pyridone photochemistry is mostly singlet-derived. 6 A singlet process for the photocycloaddition of 3 would be consistent with the retention of (E) alkene geometry observed for this reaction as well as for the corresponding (Z) alkene 5, Scheme 2.In four additional examples, with hydrogen, trimethylsilyl and cyclopropyl (7a-d) terminating the alkyne, with and without bromine at C-5 of the pyridone, a clean [2+2] cycloaddition is observed, yielding the [2+2] adducts 8a-d as single isomers, Scheme 3. These reactions were typically run in NMR spectrometer tubes (3.5 mm diameter) using a 400 W medium-pressure mercury lamp in a water-cooled jacket and a Pyrex Ò filter, standardized as 0.025 M solutions of 3 or 7 in C 6 D 6 or toluene. As noted in Scheme 3 http://dx.

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