N-Acyliminium ions are highly reactive electrophilic species 1 that have been demonstrated only recently to engage successfully in asymmetric catalytic reactions. [2][3][4] Our own studies in this area led to the discovery that the chiral thiourea derivative 1a promotes highly enantioselective Pictet-Spengler-and Mannich-type reactions through initial acylation of imines and isoquinolines, respectively. 3 The process by which the resulting N-acyliminium ions are induced to undergo enantioselective additions with a simple hydrogen-bond donor catalyst such as 1a is intriguing. Two limiting mechanisms consisting of S N 1 and S N 2 pathways may be considered (eq 1), but in neither case is the mode of catalyst interaction with

The medicinal chemistry subgroup of the American Chemical Society's Green Chemistry Institute Pharmaceutical Roundtable (ACS GCI PR) offers a perspective on the current state of environmentally sustainable practices in medicinal chemistry with the aim of sharing best practices more widely and highlighting some potential future developments.

The catalytic, asymmetric syntheses of quinine and quinidine were achieved in 16 steps. The recently developed salen(Al)-catalyzed enantioselective Michael addition of methyl cyanoacetate served to set the crucial C4 stereocenter in 92% ee, and a late-stage asymmetric dihydroxylation was used to differentiate the common intermediate and access the two desired diastereomeric products with high selectivity.

A series of studies is presented to characterize the photophysical properties of a novel type of aggregate formed by the spontaneous noncovalent assembly of numerous cofacial dimers of cyanine dyes (DiSC 3+ (5)) to the minor groove of poly(dI-dC) DNA. The dimensions of these helical aggregates, first synthesized and characterized by Armitage and co-workers (J. Am. Chem. Soc. 2000, 122, 9977-9986), are restricted to the width of the dye dimer because of steric constraints in the minor groove, though the length of the aggregate can extend essentially for the full length of the DNA template. These unique species exhibit both H-and J-type absorption bands that are shifted from the absorption maximum of the monomeric dye by +1650 and -1275 cm -1 , respectively, because of the stacking interactions between the dyes composing the dimers. Additional splittings are seen because of head-to-head interactions between adjacent dye dimers. Here, we present the low-temperature (77 K) absorption, fluorescence, and electroabsorption spectra of these aggregates as well as measurements of the fluorescence lifetime of the monomer and of the J-type emission at 10 °C. The electroabsorption measurements yield values of the average difference polarizability on excitation, 〈∆r〉, for the H and J bands of -74 and -34 Å 3 , respectively. These are between 2 and 6 times larger than that of the monomer. Both bands exhibit similar values for the difference dipole moment on excitation (|∆µ B|) of between 0.6 and 0.7 D that are somewhat smaller than that of the monomer (1.1 D). The absorption and fluorescence experiments show that the line width of the J band is ∼4 times narrower than the experimental fwhm of the DiSC 3+ (5) monomer while the fluorescence decay of the aggregate is roughly a factor of 2 faster. Implications of all of these measurements for determining the number of dyes that are excited cooperatively upon light absorption are discussed.

The regio- and enantioselective cyclization of pyrroles onto N-acyliminium ions generated in situ from hydroxylactams is reported. Modest to excellent ee's and yields are obtained in these novel Pictet-Spengler-type reactions with a chiral thiourea-pyrrole catalyst. Useful synthetic transformations of the versatile pyrroloindolizidinone and pyrroloquinolizidinone products are presented.