Reports: B447422-B4: Synthesis, Thermal, and Photochemical Reactivity of Highly Conjugated Enediynes

John D. Spence , California State University (Sacramento)

Goals:  Thermal and photochemical C1-C6 Bergman and related C1-C5 cyclizations of enediynes have a wide range of applications from DNA cleaving agents to polymer chemistry and syntheses of carbon rich materials.  Our group is currently exploring the effect of extended conjugation on the reactivity of arenediynes.  In this work, we have developed three synthetic routes to prepare highly conjugated enediyne chromophores to examine thermal and photochemical reactivity.  In year three our focus was on further exploring the syntheses and reactivity of arylethynyl and butadiynyl arenediyne derivatives.

Results:  Our work on the syntheses and photochemical reactivity of symmetrical 1,2-bis(arylethynyl)benzene derivatives has led to the discovery of a novel [2+2] photodimerization previously unreported for arenediynes.  The presence of naphthalen-1-yl and phenanthren-9-yl substituents lead to these new macrocycles upon irradiation at 350 nm while no C1-C6 or C1-C5 enediyne cyclization is observed in these derivatives at 350 or 300 nm.  To further examine this chemistry we have prepared 2-methoxynaphthalen-1-yl and 4-methoxynaphthalen-1-yl derivatives as examples of electron rich arylethynyl arenediynes.  Preliminary data indicates improved [2+2] cycloaddition yields are obtained for the 4-methoxynaphthalen-1-yl derivative.  We are currently optimizing reaction yields and examining absorbance/emission properties of arenediynes that lead to this novel cycloaddition.  In comparison, naphthalen-2-yl and 6-methoxynaphthalen-2-yl derivatives do not show reactivity at 350 nm; however, the electron rich 6-methoxynaphthalen-2-yl derivative exclusively affords C1-C6 Bergman cyclization upon irradiation at 300 nm.  In effort to further improve C1-C6 photocyclization yields we have prepared the related mono arylethynyl derivatives from 4-methoxynaphthalen-1-yl and 6-methoxynaphthalen-2-yl from 1-bromo-2-iodobenzene in three steps.  Preliminary results indicate these substrates give similar photo-reactivity as their disubstituted counterparts with significantly reduced irradiation times.  Finally, we are currently elucidating the complex product mixture from irradiation of the anthracen-9-yl derivative at 300, 350, and 419 nm. 

In a second approach to extend conjugation to the enediyne core we previously prepared 1,2-bis(phenylbutadiynyl)benzene as a novel enetetrayne derivative.  Though this compound gave promising solid state thermal reactivity by DSC, we have been unable to isolate solution thermal or photochemical cyclization products from this derivative.  In effort to improve cyclization yields we have prepared the related 1-ethynyl-2-(phenylbutadiynyl)benzene derivative in three steps from 1,2-diiodobenzene.  Compared to the tetrayne model, the enetriyne undergoes a modest thermal C1-C6 Bergman cyclization when heated to 220 °C in the presence of 1,4-cyclohexadiene.  We are currently exploring the photochemical reactivity of this system where the additional alkynyl unit increases absorbance out to 350 nm.

Finally, we have completed our work on the syntheses and thermal reactivity of terminal aryl-fused quinoxalenediynes which undergo thermal C1-C6 Bergman cyclization.  A manuscript describing this work is currently in preparation.  Computational and photochemical studies on phenylethynyl and cyclic derivatives of this family of highly conjugated arenediynes will be completed during a one year time extension.

Impact on Undergraduates:  Over the past three years a total of thirteen undergraduate chemistry majors have worked on this project.  Eleven students have participated in summer research, with each student working an average of three semesters.  Of the seven students who have graduated, three are in graduate programs in chemistry, two are employed in local chemistry related industry, one entered pharmacy school and one has entered medical school.  Overall, nine presentations have been given at national ACS meetings and thirteen presentations have been given at regional undergraduate research symposia.  Finally, three undergraduate students are listed as co-authors on peer reviewed publications with additional undergraduates listed as co-authors on manuscripts in preparation.  For these students, participation in research provides a valuable learning experience that cannot be matched in the classroom.  Participation in summer research would not be possible without support from this grant.

Impact on PI's Career:  As a PI at a primarily undergraduate institution, conducting quality research with undergraduate chemistry majors is one of my primary responsibilities.  Funding provided by ACS-PRF has supported thirteen students, resulted in twenty-two presentations, one publication and two manuscripts in preparation to be completed during one year time extension.  In addition, this grant has facilitated additional funding from campus in the form of release time to conduct scholarship activities as well as external funding from the NSF-MRI program to support a new 500 MHz NMR which undergraduate research students use routinely.  Finally, in conjunction with this award, I have established collaborations with Dr. Benjamin Gherman (computational chemist) and Dr. Marilyn Olmstead (x-ray crystallographer) that have advanced my research program beyond traditional organic chemistry. 

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