Trapping of Carbenes using DMF or DMSO Jens Wutke and Klaus Banert a a Chemnitz University of Technology, Institute for Chemistry, Organic Chemistry Straße der Nationen 62, D-09111 Chemnitz, Germany Introduction Experimental proceeding in the laboratory: Variation of the amount of used azide (1,2,10 eq referring to 1) Investigation of the influence of water Marking experiments using D 2 17 O Synthesis of proposed intermediates and their reaction under usual conditions (rt, 3 d, DMF) Attempts to trap assumed intermediates from the reaction of 1 with ionic azides in dimethylformamide We thank Dipl.-Chem. Dieter Schaarschmidt, Dr. Tobias Rüffer and Dr. Petra Ecorchard (Inorganic Chemistry, Chemnitz University of Technology) for the X-ray crystal structure measurements. We are also very thankful to Dr. Manfred Hagedorn for his support of our work. [1] W. Kirmse, Carbene, Carbenoide und Carbenanaloge, Verlag Chemie, Weinheim, 1969. [2] A. J. Arduengo III, R. L. Harlow, M. Kline, J. Am. Chem. Soc. 1991, 113, 361. [3] K. Banert, M. Hagedorn, J. Wutke, P. Ecorchard, D. Schaarschmidt, H. Lang, Chem. Commun., in preparation. [4] A. A. Auer, E. Prochnow, K. Banert, J. Phys. Chem. A 2007, 111, 9945–9951. [5] F. Dost, J. Gosselck, Tetrahedron Lett. 1970, 11, 5091–5093. Mechanistical Investigation (Formation of 10) Summary Carbene Trapping Structures Possible Mechanistical Pathways to 10 Inter- and Intramoleculare Carbene Trapping Molecular structure of 9b (R = p-CH 3 –C 6 H 4 –) Molecular structure of 7a (R = Ph–) Quantum-chemical calculations have shown that the corresponding nitre- ne structure resulting from 2 does not meet an energetic minimum. [4] Several mechanisms can be postulated to ex- plain the formation of the α-oxo amides 10. We have shown that nitrile 11a is converted into 10a in up to 8 % yield, what give reason to suspect an insertion of the carbenes 5 into the (sp 2 )-CH-bond of DMF as a possible reaction pathway. Molecular structure of 10c (R = p-Ph–C 6 H 4 –) Molecular structure of 11a Molecular structure of 9e Molecular structure of 20 Within our attempts to synthesize 1-azido-1-alkynes 2, [3] we have demonstrated that these compounds are highly reactive species leading to carbene structures 5 which have successfully been trapped as shown below. Whereas widely used trapping agents such as cyclohexene ( 6), tolane ( 7) and cyclooctyne ( 8) gave no or only small amounts of carbene trapping products, we have been able to show polar solvents such as DMSO ( 9) and DMF ( 10) to be suitable reagents for “catching” the intermediates 5 in moderate yields. Carbenes are short-lived neutral species containing a carbon atom with only six valence electrons. Thus, they are electron-deficiency compounds, which are able to take part in several kinds of reactions, such as the formation of three-membered rings, insertions or ring enlargement reactions, for instance. [1] Although persistent carbenes are known (Arduengo carbenes), [2] most members of the carbene family are highly reactive intermediates which have to been proved by defined trapping products, due to their reactivity. However, the generation of carbe- nes can easily be performed using diazoalkanes, ketenes, diazirines or α-elimination. On the other hand, the formation of heterocycle 20 might be a result from an intramo- lecular reaction based on the cor- responding oxirane 14d. Although the reaction of carbenes with DMSO has already been described in literature, [5] a trapping of car- benes using DMF has surprisingly not been reported, yet. R Cl R = CH 2 OTHP DMF rt, 3 d NaN 3 O O NMe 2 R = CH 2 OH DMF rt, 3 d NaN 3 53% 34% O O O NMe 2 O DMSO rt, 3 d NaN 3 1 R 9 CN S Me Me O = THP (tetrahydro- pyran-2-yle) a d e 10e R = CH 2 OH NaN 3 OH 5d CN intramolecular reaction up to 4.8% O CN Cl CHO HCN 52% 19 18 20 R = H R = CH 2 OH R = CH 2 OTHP 10% 3.9% 25% DMSO rt, 2 d 14% sulfolane We have been able to show DMSO as well as DMF to be suitable agents for the trapping of carbenes but in the last case the reaction might be limited to carbenes bearing a good leaving group in α-position. Whereas the formation of sulfoxonium ylides 9 is easily understandable, the reaction involving dimethylformamide yielding α-oxo amides 10 is still not understood completely. We postulated several possible reaction pathways and tried to identify different intermediates regarding to the confirmation of these mechanism. A few tests including 17 O marking experiments are still in progress to achieve certain knowledge. © Timo Pries, http://www.comic-labor.de –NaCl Ph Cl Ph CN mechanism 1: insertion into the (sp 2 )-CH-bond of DMF Me 2 N O H Ph CN NMe 2 H O mechanism 2: addition to the CO- bond of DMF Ph CN O H NMe 2 Me 2 N O H 1a Ph Nu NMe 2 H O Ph NH NMe 2 O H 2 O Nu – –CN – Ph O Nu NMe 2 H Ph O NH NMe 2 Nu=N 3 –N 2 H 2 O Nu=OH oxidation 5a Nu – –CN – Nu=N 3 –N 2 Ph NMe 2 O O 11a 12a 13a 14a 15a 16a Nu=OH oxidation 10a N N Ph Br 17 TBACN DMF rt, 3d up to 13% NaN 3 –N 2 up to 21% (from 1a) DMF R Cl R N 3 N 3 – –Cl – R CN R CN N N –N 2 –N 2 R Br N N TBACN 1 2 3 4 5 R CN 6 not observed tolane R CN 7 a R=Ph 1.2% Ph Ph R CN 8 up to 2.3% cyclo octyne DMSO R CN 9 up to 25% R O 10 up to 53% DMF S H 3 C CH 3 O O N(CH 3 ) 2