Control of the Intramolecular [2+2] Photocycloaddition in a Bis-Stilbene Macrocycle Yuewen Xu, † Mark D. Smith, † Jeanette A. Krause, ‡ and Linda S. Shimizu* ,† Department of Chemistry and Biochemistry, UniVersity of South Carolina, Columbia, South Carolina 29208, and The Richard C. Elder X-ray Crystallographic Facility, Department of Chemistry, UniVersity of Cincinnati, Cincinnati, Ohio 45221 shimizul@mail.chem.sc.edu ReceiVed February 26, 2009 The intramolecular [2+2] photocyclization of a bis-stilbene macrocycle was studied. The reaction can be controlled by the insertion and removal of urea protecting groups. Upon UV-irradiation in both the solid state and DMSO solution, the free urea macrocycle undergoes a cis-trans photoi- somerization that is followed by a [2+2] cycloaddition to afford a single product in high yield. The presence of the triazinanone urea protecting groups does not alter the cis- trans photoisomerization but greatly decreases the selectivity of the photocycloaddition step. The [2+2] cycloaddition reaction has been one of the most efficient and stereoselective methods for synthesizing cyclobu- tane derivatives in the solid state. 1 However, in solution it is more difficult to control both yield and stereoselectivity of the process. Olefins such as stilbene typically afford a mixture of products upon UV-irradiation in solution. 2 Supramolecular 3 and covalent approaches, which fix two stilbene units within macrocyclic frameworks, 4 have the potential to exert greater control over the photodimerization of stilbene derivatives. We report herein that subtle conformational effects can be used to control the selectivity of an intramolecular [2+2] photoaddition of stilbenes in solution. This paper describes the synthesis of a bis-urea macrocycle containing two cis-stilbenes. The presence or absence of a triazinanone urea protecting group exerts surprising effects on the reaction of these macrocycles. Upon UV irradiation both macrocycles appear to undergo a cis-trans photoisomerization. However, only the unprotected urea mac- rocycle affords a single product for the subsequent [2+2] cycloaddition, the cis,trans,cis-cycloadduct in high conversion. In contrast, UV irradiation of the triazinanone protected urea macrocycle gives a complex mixture of products. We study the reasons for this marked difference in selectivity. Bis-stilbene macrocycle 5a was synthesized from commercial dimethyl cis-stilbene-4,4′-dicarboxylate 1a (Scheme 1). First, the diester 1a was reduced to diol 2a. Bromination of diol 2a with NBS/PPh 3 yielded dibromide 3a. 5 The dibromide 3a was cyclized with the triazinanone in NaH/THF to afford the protected cis-macrocycle 4a. 6 The protecting group was removed with use of diethanolamine in methanol to yield target macro- cycle 5a. 7 The trans-stilbene macrocycle was prepared by a similar route starting with trans-stilbene 1b. We used X-ray crystallography to compare the solid state structures of compounds 4a and 5a. Single crystals of 4a were obtained by slow diffusion of hexane into a THF solution of 4a. In the X-ray crystal structure (Figure 1a), the tert-butyls of the protecting groups are positioned above and below the macrocyclic plane. The two urea groups are aligned in opposite directions, which minimizes the dipole interactions. The distance between the two stilbene double bonds was 13.4 Å, which should be too distant for an intramolecular [2+2] cycloaddition. † University of South Carolina. ‡ University of Cincinnati. 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