SYNFORM is available as part of the online editions of SYNTHESIS, SYNLETT and SYNFACTS through Thieme eJournals. This supplementary feature is available free of charge. SYNFORM presents people, trends, and views in synthetic organic chemistry with direct links to all quoted original papers. To view or download issues of SYNFORM, please click here.
I know that my impression is based on very partial and subjective data, and I am well aware that such things as global warming and the greenhouse effect are scientifically proven and (unfortunately) absolutely true, but judging from the weather we’ve had in the last few weeks I would rather say that we are heading towards a new glacial era here in Scotland... High winds, snow blizzards, ice and only a few minutes of sunshine in the last few weeks... Normally I am not a big fan of warm weather, but recently I have been dreaming of a tropical beach, or even better the wonderful sea of my beloved Sardinia in a hot summer... Just a dream unfortunately, still several months ahead before such things may materialize. Let’s be realistic then, and think about the good things we have right here, right now. A new issue of SYNFORM for example, what else!! We have an outstanding first SYNSTORY on the use of an industrial by-product, fluoroform, for performing trifluoromethylation reactions according to the methodology developed by Professor S. Prakash and the Nobel laureate Professor G. Olah (USA). The second SYNSTORY brings us into the realm of catalytic enantioselective amination of terminal olefins, in the new version developed by Professor U. K. Tambar (USA). The third SYNSTORY covers the enantioselective synthesis of 1,1-cyclopropane diesters discovered by Professor Y. Tang (P. R. of China). Last but not least, the issue is completed by the Young Career Profile on Professor M. D’hooghe (Belgium).
The trifluoromethyl group is a key structural element present in a large number of pharmaceuticals, agrochemicals and materials. Nucleophilic trifluoromethylation is one of the most commonly used methods to introduce a trifluoromethyl group into an electrophilic substrate utilizing (trifluoromethyl)trimethylsilane, TMS-CF3, the Ruppert–Prakash reagent developed in 1989. This reagent is currently synthesized from CF3Br (a gas) and its use is highly regulated in the western world due to the Montreal protocol on ozone-depleting CFCs. Hence, production of this important reagent is becoming difficult and expensive and is only taking place in countries such as Ukraine and P. R. of China. The recent Science paper by Professor G. K. Surya Prakash and co-workers as well as Professor George Olah of the Loker Hydrocarbon Research Institute, University of Southern California (USA), appears to crack this important and long-standing problem.
Chiral amines represent an important sub-class of medicinally relevant nitrogen-containing molecules, and nitrogen-containing chemical structures are ubiquitous in functional materials. Furthermore, nitrogen-containing moieties are key components of a number of FDA-approved pharmaceutical drugs. Most enantioselective methods for the synthesis of chiral amines are dependent on the pre-functionalization of hydrocarbons, including olefins, into reactive electrophiles, such as allylic halides and alcohols. It is therefore not surprising that the direct conversion of olefins into chiral amines through an enantioselective allylic amination reaction has remained an important goal in chemistry for many years. In particular, the direct allylic amination of unactivated olefins represents a highly practical, economically efficient, and environmentally benign alternative for accessing chiral amines. Unsaturated hydrocarbons are ideal substrates for chemical synthesis, because they are inexpensive and abundant components of petrochemical feedstock. However, olefins are also challenging substrates for asymmetric catalysis, because it is difficult to selectively transform a single C–H bond into a C–N bond in the presence of several sterically and electronically similar C–H bonds. Professor Uttam K. Tambar and Hongli Bao at the University of Texas Southwestern Medical Center (Dallas, USA) recently developed a catalytic enantioselective allylic amination of unactivated terminal olefins via an ene reaction/[2,3]-rearrangement.
Optically active 1,1-cyclopropane diesters are valuable chiral intermediates in total synthesis due to their versatile reactivity, the presence of two geminal ester functions, and the preservation of stereochemical information in most transformations. Chiral sources or kinetic resolutions of racemic cyclopropanes are methods frequently employed to synthesize these compounds. The research group of Professor Yong Tang of the Shanghai Institute of Organic Chemistry (P. R. of China) has recently investigated an alternative method. Professor Tang said: “In comparison with other methods, asymmetric cyclopropanation of olefins with malonate-derived metallocarbenes has the potential to provide the most straightforward synthetic route.”
Background and Purpose. SYNFORM will from time to time meet young up-and-coming researchers who are performing exceptionally well in the arena of organic chemistry and related fields of research, in order to introduce them to the readership. This SYNSTORY with a Young Career Focus presents Professor Matthias D’hooghe, Ghent University, Belgium.
Is it just me, or are weekends actually tougher than the normal Monday to Friday working week? I don’t know you, but most of my weekends are simply exhausting. It typically starts with a rush to the supermarket for the weekly shopping, then there is my son’s first football match, the one with the school’s team. It’s something I really enjoy, so I never miss it. Then I prepare the lunch while my wife takes care of the little footballer’s shower and my daughter obviously does nothing to help... Then, there is either the house cleaning or, if I am under pressure with my academic job, I will escape to my office. Then, I’ll prepare the dinner, load the dish-washer and finally, on an ideal Saturday night, I’ll collapse on the couch to watch a well-deserved TV movie with my favorite single malt. On Sunday, it’s even tougher. It starts early with my son’s second football match, this time with his official team, which often involves a short journey to a neighboring village. Then back home for lunch, tidying up, then Sunday afternoon is usually SYNFORM's time (which I really enjoy). When I am done, I take care of the dinner (Italians don’t like take-away food, not even when they are in Scotland, they always cook...), final tidying-up of dining room and kitchen, and finally... well this is actually a secret. Do you know what happens on Sunday night? I check the scores of my Fantasy Football Team! Oh yes! It’s a lot of fun, and I really enjoy playing against my old Italian colleagues and friends. Finally, it’s bed time. It’s almost Monday, at last! Now, more seriously, let’s have a look at this new issue of SYNFORM. We start with a new quaternary-carbon forming process developed by Professor C. H. Larsen (USA). We continue with a very convenient novel Staudinger-type amide-bond formation reported by Professor B. Ashfeld (USA). The third SYNSTORY covers the regioselective synthesis of highly functionalized furans discovered by Professor P. Zhang (USA). The issue is completed by a Young Career Focus on Professor J. Wu (USA). By the way, luckily not all of my weekends are like the one described above...
Three-component couplings (3CC) of aldehydes, amines and nucleophiles are ubiquitous and extremely versatile; however, the use of ketones is notoriously challenging. In 2007, Prakash and Olah unveiled that gallium(III) triflate catalyzed the first direct 3CC Strecker reaction of ketones in the Proceedings of the National Academy of Sciences. Terminal alkynes as nucleophiles provide propargylamines, which display an impressive range of therapeutic activity from achiral hypertensives to chiral HIV reverse transcriptase inihibitors. Similarly, amines on fully substituted carbon centers are found in many natural products and bioactive compounds. However, ketones could not be utilized as electrophiles in these 3CC because of the high barrier to in situ ketimine formation as compared to spontaneous condensation to aldimine. Stoichiometric metal-acetylide additions to isolated ketimine represented the prior route to these compounds. The recent communication from the research group of Professor Catharine Larsen from the University of California, Riverside (USA) (covered in this SYNSTORY) bridges the synergistic chemical potential of amines and acyclic ketones by providing an efficient catalytic route to synthesize propargylamines bearing fully substituted carbon centers directly from unactivated ketones. Professor Larsen said: “The value of our method is derived from the difficulty presented by the corresponding 3CC of an acyclic ketone, an amine and a nucleophile.”
The interconversion of carboxylic acid derivatives through nucleophilic acyl substitutions represents one of the most fundamental transformations in synthetic organic chemistry. One of the most widely utilized strategies for functionalization involves the dehydration of carboxylic acids via an activated acyl intermediate. Unfortunately, difficulties with product purification, the need for oftentimes caustic reagents, generally acidic conditions, and poor atom-economy of the dehydration process are several of the drawbacks to this approach. To address these issues, recent efforts in Brandon Ashfeld’s research group at the University of Notre Dame (Indiana, USA) have focused on the development of alternative catalytic dehydration methods, as well as on the direct use of carboxylic acids as substrates for this transformation.
The furan ring is present in a broad range of natural and/or bioactive molecules; furthermore, it constitutes a versatile synthetic building block susceptible to both reduction and oxidation reactions, as well as to a variety of ring-opening processes. Although the first synthesis of a furan dates back to 1780 (2-furoic acid), the synthesis of complex molecules containing the furan ring continues to represent a very active and stimulating area of organic chemistry. One conceptually novel strategy for the synthesis of highly functionalized furans, as well as oligofurans, has recently been reported by the research group of Professor Peter Zhang at the University of South Florida (Tampa, USA).
Background and Purpose. SYNFORM will from time to time meet young up-and-coming researchers who are performing exceptionally well in the arena of organic chemistry and related fields of research, in order to introduce them to the readership. This SYNSTORY with a Young Career Focus presents Professor Jimmy Wu, Dartmouth College, Hanover, NH, USA.