Written by: Dr. Sharbil J. Firsan

A “greener” method for the preparation of phosphonium chlorides directly from benzyl alcohols in water, rather than from benzyl chlorides in dioxane in the presence of triethylamine, has been reported by James and co-workers of the University of British Columbia.  The significance of this study lies in the use of water-soluble phosphines as excellent bleaching and brightness-stabilization agents for pulps.  The scope and limitation of the reaction of a series of tertiary phosphines and benzyl alcohols was investigated, and was found to give the corresponding isolated phosphonium chlorides in good-to-excellent yields.  It was also observed that an ortho or para hydroxyl substituent in the aromatic ring is required for the reaction to take place, consistent with a mechanism involving initial carbocation formation, followed by formation of a resonance-stabilized quinone methide intermediate.

(1) Moiseev, D. V.; Patrick, B. O.; James, B. R. Inorg. Chem. 2009, 48, 239.  (2) For a recent review on transition-metal-catalyzed cross-couplings in water, see Lipshutz, B. H.; Ghorai, S. Aldrichimica Acta 2008, 41, 59.

Written by Louis-Charles Campeau Ph. D.
Senior Research Chemist
Process Research & Development
Merck FrosstCentre for Therapeutic Research

 The prevalence of indoles in natural and medicinal bioactive compounds has stimulated much interest in the development of synthetic methods for their preparation.  Recently, Fagnou and co-workers have discovered that oxidative coupling of acetanilides with di-substituted alkynes using Rhodium catalysis provides good  yields of the corresponding indole products.  This novel reactivity allows for a broader range of readily available starting materials to be used, as simple anilines can be easily acetylated to provide the aryl building block.  The authors demonstrated this by coupling a number of substituted acetanilides and alkynes.  Good regioselectivity was demonstrated when more than one indole isomer could be formed. 

 

Written by: Lisa M. Roth, Ph.D.

I recently read an interesting article about how critical it is to utilize stable isotope labeled bioactive compounds as internal standards for quantitative GC-MS assays. The article demonstrates that it is important to consider the type and location of the stable isotope in the internal standard.  The researchers were conducting equine urinalysis for local and overseas racing authorities using testosterone-16,16,-17-d₃ as an internal standard.  They observed a consistent false positive in a biological sample that had specific enzymatic and microbial content.  Through further research, they demonstrated that the internal standard was undergoing oxidation followed by H/D exchange to form the analytes resulting in the false positive analysis.  The authors emphasize the need for caution when using internal standards and recommend not including internal standards when performing a qualitative confirmatory test.  However, an alternative to consider in this situation, would be to use to an internal standard where the isotope cannot be exchanged, for example testosterone-2,3,4-¹³C₃.  Using this material would preserve the M+3 mass shift and hopefully make it easier to prevent false positives from occurring due to this reaction pathway. 

Reference:

Rapid Communications in Mass Spectrometry.22:682-686,2008.Wok WH, et al. Unusual observations during steroid analysis.

Today is Ada Lovelace Day, an international day of blogging to draw attention to women excelling in technology. Women's contributions often go unacknowledged, their innovations seldom mentioned, their faces rarely recognized.

Here's just a couple of the great posts I found.

An interview with Dr. Kristen Kulinowski, Director of the International Council On Nanotechnology http://bit.ly/unPId

Marie Curie 2.0: The Greatest Woman Scientist in History: http://tinyurl.com/c4c9r6

Written By: Mark Redlich, Ph.D.

Here is a communication in JACS I recently came across that highlighted the metal-free cross-coupling of unfunctionalized heterocycles.  The reaction is mediated by a stochiometric quantity of a hypervalent iodine(III) reagent and displays a broad substrate scope under mild conditions. Interestingly, the methodology allows for the selective cross-coupling of two arenes that have closely related structures to give the mixed biaryls in high yield and regioselectivity without any detectable oligomerization.

Kita, Y. et al. J. Am. Chem. Soc. 2009, 131, 1668.

I came across this incredibly useful and straight-forward asymmetric preparation of allylic amines in the ASAP articles of the Journal of the American Society. The efficient asymmetric preparation of allylic amines has been a longstanding challenge in organic chemistry. While the Rh(I)-catalyzed addition of arylboron reagents to activated imines has been demonstrated, the analogous addition of alkenylboron species to activated imines to provide allylic amines remained unprecedented until now. Brak and Ellman have now shown the addition of alkenyl trifluoroborates to both aromatic and aliphatic activated N-tert-butylsulfinyl imines using a catalyst comprised of [Rh(OH)(cod)]₂, and dpp-benzene, in the presence of NEt₃ and H₂O/DMF. The scope is quite broad, with respect to both coupling partners, incorporating variously substituted amines and both di-and tri-substituted olefinic trifluoroborates, in all cases providing the allylic amines with excellent diastereoselectivity. What is also worth mentioning is the analogous transformation with a boronic acid instead of the trifluoroborate salt provided the product, albeit in low yield; thus, key to this chemistry is the use of the stable boronic acid surrogate trifluoroborate salts. This method is likely to be quite useful to the chemist for the facile and stereoselective prepararion of allylic amines.

Brak, K.; Ellman, J. J. Am. Chem. Soc. ASAP.

A while back I had heard that MIT (Massachusettes Institite of Technology) was going to be offering FREE classes on line. I was really excited to hear this and had to check it out. What I discovered is that they offer over 1800 courses in a range of interest areas including Chemistry.

MIT OpenCourseWare (OCW) is a web-based publication of virtually all MIT course content. It's open and available to the world and is a permanent MIT activity. They offer free lecture notes, exams, and videos, all with no registration required. What this does NOT get you is an MIT education, they do not grant degrees or certificates from these online courses and you are not given access to MIT faculty. But still, great content for anyone who loves learning for the sake of learning.

My personal philosopy - A day without learning something new is a wasted day. Think I'll head over and learn something new!