Reports: B4
47422-B4 Synthesis, Thermal, and Photochemical Reactivity of Highly Conjugated Enediynes
Goals: Thermal and photochemical Bergman and related cyclizations of (Z)-hexa-3-ene-1,5-diynes, or enediynes, have a wide range of applications from DNA cleaving agents to materials chemistry. Our group is currently exploring the effect of increased conjugation on enediyne reactivity. In this work, we have developed three routes to prepare highly conjugated enediyne chromophores to study thermal and photochemical reactivity. In the first year of this grant we focused studies on our arylethynyl enediyne and enetetrayne model systems.
Results: In our preliminary work, we prepared 1,2-bis(naphthalen-1-ylethynyl)benzene as a model arylethynyl enediyne which extends conjugation to the enediyne chromophore through the alkyne substituent. Our synthetic efforts have since expanded to include a series of arylethynyl enediynes possessing naphthalen-2-yl, 4-methoxynaphthalen-1-yl, 6-methoxynaphthalen-2-yl, phenanthren-9-yl, and anthracen-9-yl groups as the alkynyl substituent. Upon completing the syntheses, we have examined the thermal and photochemical reactivity of this series of arylethynyl enediynes. The thermal reactivity was monitored in the solid state by differential scanning calorimetry. As anticipated, each arylethynyl enediyne required higher temperature to undergo cyclization compared to 1,2-bis(phenylethynyl)benzene due to increased steric hindrance. Interestingly, we discovered diverse photoreactivity for this system. We initially examined the photoreactivity of 1,2-bis(naphthalen-1-ylethynyl)benzene at 300 nm and 350 nm. While no reaction was observed at 300 nm, irradiation at 350 nm produced a modest yield (10-30%) of a mixture of two photo-adducts, neither of which were determined to be from Bergman or related enediyne cyclization. Instead, a sequential 2+2 photocyclization between the alkyne pi-bond of one enediyne with the C1-C2 naphthalene bond of a second enediyne occurred, followed by a second intramolecular alkyne-naphthalene 2+2 cyclization. This produced a diastereomeric mixture of bis-cyclobutene dimers confirmed spectroscopically and through X-ray crystallographic analysis. In comparison, 1,2-bis(naphthalen-2-ylethynyl)benzene does not react at 350 nm yet affords a C1-C6 Bergman cyclization product at 300 nm in low yields (<5%). Initial studies on the methoxynaphthyl derivatives indicate improved crude yields relative to starting material (by 1H NMR) of cyclobutene derivatives for 1,2-bis(4-methoxynaphthalen-1-ylethynyl)benzene and C1-C6 Bergman cyclization for 1,2-bis(6-methoxynaphthalen-2-ylethynyl)benzene. Finally, the phenanthren-9-yl derivative similarly affords cyclobutene dimers at 350 nm (20%) while the photoreactivity of the anthracen-9-yl system is currently under investigation. A manuscript describing the syntheses and reactivity of naphthalene-1-yl and naphthalene-2-yl enediynes is currently in preparation.
In a second approach to extend conjugation to the enediyne core, we are exploring the novel enetetrayne, 1,2-bis(4-phenylbuta-1,3-diynyl)benzene, and the related enetriyne, 1-ethynyl-2-(4-phenylbuta-1,3-diynyl)benzene. Differential scanning calorimetry studies indicate these substrates are more reactive thermally compared to 1,2-bis(phenylethynyl)benzene. Indeed, solution thermal cyclization of the enetriyne at 200 °C in the presence of 1,4-cyclohexadiene affords a modest yield (25%) of the C1-C6 cyclization product 2-(phenylethynyl)naphthalene. In addition, solution cyclization of the enetetrayne affords 2,3-bis(phenylethynyl)naphthalene in low yields (5%). Studies to understand the photochemical reactivity of these two substrates are currently ongoing in our lab.
Collaborations: We have continued our collaboration with Marilyn Olmstead at the University of California, Davis, X-Ray Crystallography Facility. This collaboration was instrumental in solving the structure of the 1,2-bis(naphthalen-1-ylethynyl)benzene photoadducts. In addition, we initiated a collaboration with our departmental computational/physical chemist, Benjamin Gherman. In these studies, we are computing the activation barrier towards C1-C6 Bergman and the related C1-C5 cyclization of naphthylethynyl enediynes to better understand the diverse reactivity of this system. In addition, we are examining the influence of electron donating (methoxy) and electron withdrawing (nitro) groups located on the naphthalene substituent on enediyne reactivity.
Undergraduate Training: Funding from this project provided supplies and materials to support 8 undergraduate research students during the 2008-2009 academic year along with 3 summer stipends (4 additional students were supported in the summer with campus funding). This work resulted in 3 posters at National ACS meetings in addition to 8 presentations at local meetings.
