Among carbon, hydrogen, oxygen, and nitrogen, sulfur and fluorine are both leading constituents of the pharmaceuticals that comprise our medicinal history. In efforts to stimulate the minds of both the general public and expert scientist, statistics were collected from the trends associated with therapeutics spanning 12 disease categories (a total of 1969 drugs) from our new graphical montage compilation: disease focused pharmaceuticals posters. Each poster is a vibrant display of a collection of pharmaceuticals (including structural image, Food and Drug Administration (FDA) approval date, international nonproprietary name (INN), initial market name, and a color-coded subclass of function) organized chronologically and classified according to an association with a particular clinical indication. Specifically, the evolution and structural diversity of sulfur and the popular integration of fluorine into drugs introduced over the past 50 years are evaluated. The presented qualitative conclusions in this article aim to promote innovative insights into drug development.

Among the fundamental chemical transformations in organic synthesis, the [3,3]-sigmatropic rearrangement occupies a unique position as a powerful, reliable, and well-defined method for the stereoselective construction of carbon–carbon or carbon–heteroatom bonds. While many other reactions can unite two subunits and create a new bond, the strengths of sigmatropic rearrangements derive from their ability to enable structural reorganization with unmatched build-up of complexity. Recent applications that illustrate [3,3]-sigmatropic processes as a key concept in the synthesis of complex natural products are described in this tutorial review, covering literature from about 2001 through early 2009.

Stereoselective preparation of iodoalkenes from vinylsilanes is described. 1,1,1,3,3,3-hexafluoroisopropanol serves as a unique solvent that ensures high yields and stereoselectivities in the iododesilylation of a variety of functionalized substrates.

A direct ruthenium-catalyzed radical chloroalkylation of N-acyl oxazolidinones capitalizing on valence tautomerism of titanium enolates has been developed. The chloroalkylation method served as the centerpiece in the enantioselective total synthesis of trichloroleucine-derived marine natural product neodysidenin.Among more than four thousand halogenated natural products identified to date, 1 neodysidenin and other trichloroleucine-derived marine metabolites comprise a unique group. 2 For the majority of chlorinated natural products, a reasonable biosynthetic pathway involving an electrophilic chlorination can be proposed. 3 On the other hand, the trichloromethyl group in neodysidenin and related compounds arises from a remarkable direct chlorination of the pro-R methyl group of L-leucine carried out by nonheme Fe II halogenases requiring oxygen, chloride, and α-ketoglutarate for their activity. 4 In contrast, availability of synthetic methods for stereoselective trichloromethylation is highly limited, 5 whereas chlorinated natural products are attracting increasing attention as targets for chemical synthesis. 6 In this communication we describe a practical, efficient method for highly stereoselective direct chloroalkylation of titanium enolates and its application in the total synthesis of neodysidenin zakarian@chem.ucsb.edu. Supporting Information Available:Experimental procedures and copies of 1 H and 13 C NMR spectra. This information is available free of charge via the Internet at http://pubs.acs.org. that can be readily adopted for the synthesis of other bioactive natural products in this class. 7 Guided by an extension of the classic Kharasch reaction8 described by Eguchi and coworkers, 9 our early efforts involved Ru(II)-catalyzed 10 redox trichloromethylation of trimethylsilyl enol ethers generated from chiral N-acyl oxazolidinones such as 1 (Scheme 1). 11 Although encouraging results were obtained with silyl ketene acetals (~50% yields, ds 3:1), the recent characterization of valence tautomerism in titanium enolates provided a conceptual foundation for the development of a direct radical chloroalkylation of N-acyl oxazolidinones. NIH Public Access 12,13The unconventional biradical character of titanium enolates described by Moreira and coworkers suggests that these intermediates should be efficient radical acceptors. 7 Indeed, when the Ti enolate derived from 1 14 was treated with BrCCl 3 in the presence of [Ph 3 P] 3 RuCl 2 as a readily available redox catalyst (7 mol%), product 2 was obtained in an essentially quantitative yield with exquisite stereocontrol (Scheme 1). The the mechanistic hypothesis in Scheme 1 is based on well-established redox activity of [Ph 3 P] 3 RuCl 2 widely used in atom-transfer radical polymerization (ATRP) 15 and is similar to that proposed by Eguchi for a related process with silyl enol ethers.9 A major advantage, however, is that the radical addition product should be stabilized by electron delocalization onto titanium, not feasible with silyl enol ethers. Th...

Ring expansion reactions of strained vinylic heterocyclic substrates have attracted the attention of the synthetic community for decades. Strategic manipulations of these organic architectures enable access to many useful synthetic intermediates. This paper highlights various methods for the ring expansion of vinyloxiranes, -thiiranes, and -aziridines described in the literature from 1964 to 2013.