TOSMIC, tosylmethyl isocyanide

TosMIC tosylmethyl isocyanide, [(p-toluenesulfonyl)methyl] isocyanide... 

TosMIC = tosylmethyl isocyanide [4-MeC6H4S02CH2NC] triflate = trifluoromethanesulfonate [CE3SO3 ]... 

After the umpolung of an aldehyde group by conversion to a l,3 dithian-2-ide anion (p. 17) it can be combined with a carbonyl group (D. Seebach, 1969, 1979 B.-T. GrO-bel, 1977 B). Analogous reagents are tosylmethyl isocyanide (TosMIC), which can be applied in the nucleophilic formylation of ketones (O.H. Oldenziel, 1974), and dichloromethyl lithium (G. KObrich, 1969 P. Blumbergs, 1972 H. Taguchi, 1973),... 

A one-step synthesis o( mtnles from carbonyls by a reductive cyanation with tosylmethyl isocyanide (TosMIC), also synthesis of 1,3-azole or of ketones... 

Van Leusen and co-workers also demonstrated the utility of dilithio-tosylmethyl isocyanide (dilithio-TosMIC) to extend the scope of the application. Dilithio-TosMIC is readily formed from TosMIC and two equivalents of n-butyllithium (BuLi) in THF at -70"C. Dilithio-TosMIC converts ethyl benzoate to oxazole 14 in 70% yield whereas TosMIC monoanion does not react. In addition, unsaturated, conjugated esters (15) react with dilithio-TosMIC exclusively through the ester carbonyl to provide oxazoles (16). On the other hand, use of the softer TosMIC-monoanion provides pyrroles through reaction of the carbon-carbon double bond in the Michael acceptor. 

Isonitrile cyclization provides a useful alternative method of the Knorr type cyclization for pyrrole synthesis. In 1972, Leusen and coworkers reported pyrrole synthesis based on the reaction of tosylmethyl isocyanide (TosMIC) with electron-deficient alkenes (Eq. 10.12).15... 

Reaction of pyrrolopyridines 241 with tosylmethyl isocyanide (TosMIC) in the presence of a phase transfer catalyst tetra- -butylammonium iodide (TBAI) provides the tricyclic pyrimidopyrrolopyrimidine derivatives 242 (Equation 30) <20000L3253, 2004JOC4974, 2005JOC4879>. 

Monosubstituted and 4,5-disubstituted oxazoles were easily obtained from aryl-substituted tosylmethyl isocyanides and aldehydes . Tosyloxazoles 107, prepared from TosMIC 106 and carboxylic acid chlorides, led to 5-substituted derivatives 108 through ultrasound-promoted desulfonylation <00JCS(P1)527>. 

The reaction of the 3-(bromomethyl)pyrazole 276 with various alkyl derivatives of tosylmethyl isocyanide (TosMIC) 277 affords the products 278 (Equation 56) and requires phase-transfer conditions for success <2005JOC4879>. This reaction was also used for the synthesis of ring system 68, but in lower yield (25%). 

Tosylmethyl isocyanide (TosMIC) and its congeners are useful and versatile building blocks for the construction of heterocyclic molecules.5 While TosMIC is available from a variety of commercial sources, substituted TosMIC reagents have suffered from the lack of general and efficient methods for their preparation. ... 

NMO NMP Nu PPA PCC PDC phen Phth PPE PPTS Red-Al SEM Sia2BH TAS TBAF TBDMS TBDMS-C1 TBHP TCE TCNE TES Tf TFA TFAA THF THP TIPBS-C1 TIPS-C1 TMEDA TMS TMS-C1 TMS-CN Tol TosMIC TPP Tr Ts TTFA TTN N-methylmorpholine N-oxide jV-methyl-2-pyrrolidone nucleophile polyphosphoric acid pyridinium chlorochromate pyridinium dichromate 1,10-phenanthroline phthaloyl polyphosphate ester pyridinium p-toluenesulfonate sodium bis(methoxyethoxy)aluminum dihydride (3-trimethylsilylethoxy methyl disiamylborane tris(diethylamino)sulfonium tetra-n-butylammonium fluoride f-butyldimethylsilyl f-butyldimethylsilyl chloride f-butyl hydroperoxide 2,2,2-trichloroethanol tetracyanoethylene triethylsilyl triflyl (trifluoromethanesulfonyl) trifluoroacetic acid trifluoroacetic anhydride tetrahydrofuran tetrahydropyranyl 2,4,6-triisopropylbenzenesulfonyl chloride 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane tetramethylethylenediamine [ 1,2-bis(dimethylamino)ethane] trimethylsilyl trimethylsilyl chloride trimethylsilyl cyanide tolyl tosylmethyl isocyanide meso-tetraphenylporphyrin trityl (triphenylmethyl) tosyl (p-toluenesulfonyl) thallium trifluoroacetate thallium(III) nitrate... 

An alternative way to synthesize imidazoles in a more flexible manner is to use a synthon. An example of such a synthon approach, is the synthesis of imidazoles using tosylmethyl isocyanide (TOSMIC). The original procedure using this synthon gave only moderate overall yields of the substituted imidazoles18, mainly due to the poor yield in the first step (figure 7). 

Isocyanides similarly upon deprotonation and alkylation give amines or ketones after hyditdysis. For example, methyl isocyanide reacts with butyllithium, allyl bromide, and aqueous acid to give 3-buten-amine. Tosylmethyl isocyanide (TOSMIC) can be deprotonated with excess sodium hydride in DMSO, alkylated twice with benzyl Inomide and hydrolyzed with acid and then base to give 1,3-diphe-nylpropanone. ... 

From the interaction at low temperatures in basic medium of an aldehyde or ketone and tosylmethyl isocyanide ( tosmic ), iV-(l-tosyl-l-alkenyl)formamides are formed. When these are dehydrated they produce 1-isocyano-l-tosylalkenes (66) which react with primary amines to form imidazoles in high yields (Scheme 35) (79RTC258). 

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