An efficient synthetic route to 2- and 2,7-substituted pyrenes is described. The regiospecific direct C-H borylation of pyrene with an iridium-based catalyst, prepared in situ by the reaction of [{Ir(μ-OMe)cod}(2)] (cod = 1,5-cyclooctadiene) with 4,4'-di-tert-butyl-2,2'-bipyridine, gives 2,7-bis(Bpin)pyrene (1) and 2-(Bpin)pyrene (2, pin = OCMe(2)CMe(2)O). From 1, by simple derivatization strategies, we synthesized 2,7-bis(R)-pyrenes with R = BF(3)K (3), Br (4), OH (5), B(OH)(2) (6), and OTf (7). Using these nominally nucleophilic and electrophilic derivatives as coupling partners in Suzuki-Miyaura, Sonogashira, and Buchwald-Hartwig cross-coupling reactions, we obtained 2,7-bis(R)-pyrenes with R = (4-CO(2)C(8)H(17))C(6)H(4) (8), Ph (9), C≡CPh (10), C≡C[{4-B(Mes)(2)}C(6)H(4)] (11), C≡CTMS (12), C≡C[(4-NMe(2))C(6)H(4)] (14), C≡CH (15), N(Ph)[(4-OMe)C(6)H(4)] (16), and R = OTf, R' = C≡CTMS (13). Lithiation of 4, followed by reaction with CO(2), yielded pyrene-2,7-dicarboxylic acid (17), whilst borylation of 2-tBu-pyrene gave 2-tBu-7-Bpin-pyrene (18) selectively. By similar routes (including Negishi cross-coupling reactions), monosubstituted 2-R-pyrenes with R = BF(3)K (19), Br (20), OH (21), B(OH)(2) (22), [4-B(Mes)(2)]C(6)H(4) (23), B(Mes)(2) (24), OTf (25), C≡CPh (26), C≡CTMS (27), (4-CO(2)Me)C(6)H(4) (28), C≡CH (29), C(3)H(6)CO(2)Me (30), OC(3)H(6)CO(2)Me (31), C(3)H(6)CO(2)H (32), OC(3)H(6)CO(2)H (33), and O(CH(2))(12)Br (34) were obtained from 2. These derivatives are of synthetic and photophysical interest because they contain donor, acceptor, and conjugated substituents. The crystal structures of compounds 4, 5, 7, 12, 18, 19, 21, 23, 26, and 28-31 have also been obtained from single-crystal X-ray diffraction data, revealing a diversity of packing modes, which are described in the Supporting Information. A detailed discussion of the structures of 1 and 2, their polymorphs, solvates, and co-crystals is reported separately.

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All-trans-retinoic acid (ATRA) and its associated analogues are important mediators of cell differentiation and function during the development of the nervous system. It is well known that ATRA can induce the differentiation of neural tissues from human pluripotent stem cells. However, it is not always appreciated that ATRA is highly susceptible to isomerisation when in solution, which can influence the effective concentration of ATRA and subsequently its biological activity. To address this source of variability, synthetic retinoid analogues have been designed and synthesised that retain stability during use and maintain biological function in comparison to ATRA. It is also shown that subtle modifications to the structure of the synthetic retinoid compound impacts significantly on biological activity, as when exposed to cultured human pluripotent stem cells, synthetic retinoid 4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ylethynyl)benzoic acid, 4a (para-isomer), induces neural differentiation similarly to ATRA. In contrast, stem cells exposed to synthetic retinoid 3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ylethynyl)benzoic acid, 4b (meta-isomer), produce very few neurons and large numbers of epithelial-like cells. This type of structure-activity-relationship information for such synthetic retinoid compounds will further the ability to design more targeted systems capable of mediating robust and reproducible tissue differentiation.

Palladium-catalyzed terminal alkyne dimerization, through oxidative homocoupling, is a useful approach to the synthesis of symmetrical 1,4-diynes. Recent investigations have suggested that this reaction might be accomplished in the absence of intentionally added stoichiometric oxidants (to reoxidize Pd(0) to Pd(II)). In this paper, we have fully addressed the question of whether oxygen (or added oxidant) is required to facilitate this process. The presence of a stoichiometric quantity of air (or added oxidant such as I2) is essential for alkyne dimerization. Excess PPh3 inhibits alkyne dimerization to enyne, which only occurs to a significant extent when the reaction is starved of oxidant. Theoretical studies shed more light on the requirement for an oxidant in the homocoupling reaction in order for the process to be theromodynamically favorable. The employment of I2 as the stoichiometric oxidant appears to be the method of choice. The dual role of Cu both in transmetalation of alkynyl units to Pd(II) and in assisting reoxidation of Pd(0) to Pd(II) is suggested.