Isocyanides TosMIC

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),... 

The use of a vinylphosphonium salt as the source of the QQ fragment instead of the more commonly employed 1,2-dicarbonyl substrate is illustrated by the pyrrole synthesis in Scheme 79b (8UOC2570). A particularly interesting feature is the intramolecular Wittig reaction with an amide carbonyl group. A very useful synthesis of pyrroles depends upon the addition of the anion of p-toluenesulfonylmethyl isocyanide (TOSMIC) to a,/3-unsatur-... 

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... 

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>. 

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%). 

Substituted oxazoles through the reaction of p-tolylsulfonylmethyl isocyanide (TosMIC) with aldehydes in protic solvents at refluxing temperatures. 

Tipson-Cohen reaction, 30, 2 Tosylhydrazones, 23, 3 39, 1 Tosyhnethyl isocyanide (TosMIC), 57, 3 Transmetallation reactions, 58, 2 Tricar bonyl(r -arene)chromium complexes, 67, 2... 

In Einzelfallen bietet sich die Ugi-Reaktion fur die Synthese bestimmter a-Amino-carbonsauren im Vergleich zu anderen Moglichkeiten als Methode der Wahl an. Beispiele sind die Herstellung von Bis-[l-carboxy-alkyl]-aminen I aus a-Amino-carbonsaure-estern8 [unter Verwendung von 4-Methyl-phenylsulfonylmethyl-isocyanid (TOSMIC)9 als Isonitril-Komponente] und die von 3-(2,5-Cyclohexadienyl)-alanin-methylamid(ll) (37% aus 3-Formylmethyl-l,4-cydohexadien)1. 

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. ... 

A useful pyrrole synthesis depends upon the addition of the anion of p-toluenesulfonylmethyl isocyanide (TOSMIC) to a,(3-unsaturated ketones or other Michael acceptors (72TL5337) (Scheme 56). 

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). 

T10425>. Through a proper use of the Suzuki-Miyamura and van Leusen oxazole synthesis it was possible to synthesize a wide variety of aromatic derivatives substituted with oxazole rings. The strategy was based on the initial synthesis of the aromatic scaffold and the subsequent reaction of the carbonyl functions with toluenesulfonylmethyl isocyanide (TosMIC) as depicted in the following scheme<07S3653>. 

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. ... 

Samanta et al. [23] conveniently synthesized the 1,5-disubstituted imidazoles (xxv) on a polymeric support using base-promoted 1,3-dipolar cycloaddition reaction of p-toluenesulfonylmethyl isocyanide (TOSMIC) with immobilized imines under microwave irradiation. 

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). 

Tosylmethyl isocyanide (TosMIC) (75 R = H), a versatile reagent in synthesis, can also be used as an acyl anion equivalent. For instance symmetrical and unsymmetrical diketones were prepared by using this TosMIC synthon (equation 40). Ketones are homologated to enones by alkylating the condensation product derived from TosMIC, followed by acid hydrolysis (Scheme 46). 1-Isocyano-l-tosyl-l-alkenes (76), formed by the reaction of TosMIC with an aldehyde or ketone, react with a primary amine or ammonia to give 1,5-disubstituted (or 5-monosubstituted) imidazoles in high yield (Scheme 47). ... 

Alkylation reactions of ot-metallo sulfones bearing another heteroatomic moiety at their a-site have been widely used in synthesis. These reactions include the alkylations of a-isocyanoalkyl sul-fones a-alkoxyalkyl sulfones (including 2-benzenesulfonyltetrahydropyrans ) a-haloalkyl or a-haloallyl sulfones, a-silylalkyl sulfones,a-sulfonylalkyP ° and a-sul-fonylalkenyl or a-triflylalkyP - sulfones. Among these compounds alkoxyalkyl phenyl sulfones (Scheme 75, entries a and and tosylmethyl isocyanide (TosMIC) have been used as... 

Methods in which imidazoles are prepared by reactions between isothiocyanates and tosylmethyl-isocyanide (TOSMIC) are discussed later (see Section 3.02.8.1.2(ii)). 

Type Ilbd cyclocondensation reactions between isocyanide-based reagents and electron deficient alkenes or alkynes provides a convenient S3mthetic approach to highly functionalized pyrroles. The cyclocondensation between tosyl methyl isocyanide (TosMic) and 1,2-bis(benzenesulfonyl)ethene provided 3,4-bis(benzenesulfonyl)p)nTole 37 <05JHC333>. 

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