No abstract

Rhodium complexes of diazaphospholane ligands catalyze the asymmetric hydroformylation of Nvinyl carboxamides, allyl ethers and allyl carbamates; products include 1,2-and 1,3-amino aldehydes and 1,3-alkoxy aldehydes. Using glass pressure bottles, short reaction times (generally less than 6 hours), and low catalyst loading (commonly 0.5 mol %), 20 substrates are successfully converted to chiral aldehydes with useful regioselectivity and high enantioselectivity (up to 99% ee). Chiral Roche aldehyde is obtained with 97% ee from the hydroformylation of allyl silyl ethers. Commonly difficult substrates such as 1,1-and 1,2-disubstituted alkenes undergo effective hydroformylation with greater than 89% ee and complete conversion for six examples. Palladiumcatalyzed aerobic oxidative amination of allyl benzyl ether followed by enantioselective hydroformylation yields the β 3 -aminoaldehyde with 74% ee.Perfect atom economy, high rates and turnover numbers under mild conditions, and the synthetic utility of the aldehyde products enable rhodium-catalyzed alkene hydroformylation to be one of the largest homogeneous metal-catalyzed processes, producing billions of pounds of achiral aldehydes per year. i In contrast, enantioselective hydroformylation is underdeveloped. Relatively few chiral rhodium catalysts effect high selectivity and useable rates for a broad range of substrates. ii,iii Chiral aldehydes are versatile synthetic intermediates, and new catalysts capable of selective asymmetric hydroformylation (AHF) could dramatically impact the synthesis of chiral molecules on research and production scales. We recently demonstrated that Bisdiazaphos 1, produced in two steps from 1,2-bisphosphino benzene and azine, and Rh(acac)(CO) 2 catalyze highly selective hydroformylation of vinyl acetate, allyl cyanide, and styrene derivatives with turnover frequencies approaching 20,000 h −1 under mild reaction conditions. iv In the present study, we demonstrate practical and selective AHF of 20 substrates comprising N-vinyl carboxamides, allyl ethers and allyl carbamates using rhodium catalysts bearing diazaphospholane ligand 1 (Figure 1). These reactions yield important chiral building blocks, including 1,2-and 1,3-amino aldehydes and 1,3-alkoxy aldehydes (Scheme 1), and follow upon the groundbreaking work of Takaya and Nozaki, who first demonstrated that AHF provides ready access to a variety of enantiopure aldehydes. v,vi AHF of readily available N-vinyl substrates provides an atom economic route to α-amino aldehydes. Under standard conditions of 140 psig synthesis gas (1:1 CO:H 2 ) in a glass stahl@chem.wisc.edu; landis@chem.wisc.edu. Supporting Information Available: Experimental details, characterization data, and conditions for the determination of enantiomeric excess. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript J Am Chem Soc. Author manuscript; available in PMC 2011 October 13. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscr...

The identification of activating mutations in NOTCH1 in 50% of T cell acute lymphoblastic leukemia has generated interest in elucidating how these mutations contribute to oncogenic Reprints and permissions information is available at www.nature.com/reprints.

Enantioselective intramolecular oxidative amidation of alkenes has been achieved using a (pyrox)Pd(II)(TFA)2 catalyst (pyrox = pyridine-oxazoline, TFA = trifluoroacetate) and O2 as the sole stoichiometric oxidant. The reactions proceed at room temperature in good-to-excellent yield (58-98%) and with high enantioselectivity (ee = 92-98%). Catalyst-controlled stereoselective cyclization reactions are demonstrated for a number of chiral substrates. DFT calculations suggest that the electronic asymmetry of the pyrox ligand synergizes with steric asymmetry to control the stereochemical outcome of the key amidopalladation step.

Probes that form covalent bonds with RNA molecules based on their chemical reactivity would advance our ability to study the transcriptome. We developed a set of electrophilic activity-based RNA probes designed to react with unusually nucleophilic RNAs. We used these probes to identify reactive genome-encoded RNAs, resulting in the discovery of a 42-nt catalytic RNA from an archaebacterium that reacts with a 2,3-disubstituted epoxide at N7 of a specific guanosine. Detailed characterization of the catalytic RNA revealed the structural requirements for reactivity. We developed this catalytic RNA into a general tool to selectively conjugate a small molecule to an RNA of interest. This strategy enabled up to 500-fold enrichment of target RNA from total mammalian RNA or from cell lysate. We demonstrated the utility of this approach by selectively capturing proteins in yeast cell lysate that bind to the ASH1 mRNA.