Amine over-alkylation side products in the synthesis of BMS-955176

Over-alkylation side products are common in the alkylation of amines by substitution. In the synthesis of the novel HIV Maturation inhibitor BMS-955176, two over-alkylation byproducts were routinely observed at the penultimate synthetic step, in which a thiomorpholine dioxide side chain was added to the core molecule by alkylation of a primary amine. These two byproducts had drastically different HPLC relative retention times, despite both containing only one additional side chain. Adding complexity to the challenge of solving their structures was the proclivity of the two byproducts to interconvert. Positive- and negative-ion HRMS, as well as isolation and 1D and 2D NMR were utilized to determine their structures. These byproducts were additionally problematic in that they led to daughter impurities at the API step.     

Regioselective formation of beta-alkyl-alpha-phenyliridabenzenes via unsymmetrical 3-vinylcyclopropenes: probing steric and electronic influences by varying the alkyl ring substituent

The synthesis of unsymmetrical (Z)-1-alkyl-3-(2-iodovinyl)-2-phenyl-1-cyclopropenes (R=Me (8 a), Et (8 b), iPr (8 c), and tBu (8 d)) and their reactions with Vaska's complex [Ir(CO)Cl(PPh3)2] and its trimethylphosphine analogue [Ir(CO)Cl(PMe3)2] were investigated. Iridabenzvalene (13/20), iridabenzene (14/21), and/or eta(5)-cyclopentadienyliridium complexes (15/22) were obtained in modest yields and were fully characterized by spectroscopic means. X-ray structural data was secured for iridabenzvalene 13 d and iridabenzenes 14 a,b,d. Whereas iridabenzenes 14 a-c were stable at 75 degrees C for 48 h, 14 d, which possesses a bulky tBu group, rearranged cleanly to cyclopentadienyliridium 15 d at 50 degrees C over 15 h and displayed first-order kinetics. The influence of the alkyl substituent on the mechanisms of iridacycle generation, isomerization, and iridabenzene regioselectivity is discussed.     

Development and Implementation of a New Industrial Internship Program in Polymer Synthesis and Processing

A new masters level internship program in polymer synthesis and processing offered in the chemistry and physics departments at the University of Oregon is described. The program is designed to meet the needs of the burgeoning number of polymer and semiconductor companies that are moving into Oregon. Students with an undergraduate degree in chemistry or physics are admitted to the one-year program. The program starts with intensive coursework in the summer. In the fall, following the successful completion of their summer coursework, the students are placed in a local industrial laboratory for a period of about nine months. During this time they gain practical experience and knowledge. The students meet with their university committee and industrial supervisors once a month to turn in progress reports and give talks on their work. The possible pitfalls in setting up an internship program are discussed.     

Triazenes: a versatile tool in organic synthesis

Triazenes (RN=N-NR'R") are a class of compounds that hold much promise in preparative chemistry as they are reactive groups which are both stable and adaptable to numerous synthetic transformations. Useful to scientists in pharmacology, total synthesis, polymer technology, and the construction of novel ring systems, to name a few areas, triazenes also have a tendency to surprise chemists with new reactions and increasing applicability. This review highlights some of the recent advances and diversity possible with these types of systems.     

Phosphinoboration of Diazobenzene: Intramolecular FLP Synthon for PN2B-Derived Heterocycles

Phosphinoboration of diazobenzene with Ph₂PBR′₂ cleanly affords products of the form Ph₂P(PhNNPh)BR′₂ ( 2 : R′₂=catechol, cat; 4 : R′₂=phenanthrenediol, quin) and shows evidence of Ph₂P(PhNNPh)Bpin 7 (pin: pinacol). The mechanism of these reactions was probed computationally and shown to proceed via intermediates involving a diazobenzene-adduct of the boron center of the PB reagent. The resulting PNNB species 2 and 4 are shown to be frustrated Lewis pairs (FLPs). Despite the presence of weakly Lewis acidic boron centers, these species react with diazobenzene. Additionally, the FLP reactivity of 2 was further probed with 4-phenyl-1,2,4-triazole-3,5-dione, 1,10-phenanthroline-5,6-dione, and benzyl azide to give unique five-, six-, and eight-membered heterocyclic rings. Thus, phosphinoboration provides a new avenue to FLPs in which donor and acceptor sites are linked by nitrogen atoms.     

Zur Analyse des ?thylalkohols

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