Abstract:The title compound (6) was synthesized by the base-induced condensation of 3-(isocyanotosylmethyl)benzaldehyde as a new bifunctional reactant for the synthesis of [2n]metacyclophanes. The treatments of 6 with silver triflate in several molar ratios in THF at room temperature afforded only 2:1 silver triflate complex on the basis of the 1H NMR and the analytical data.
“…The facility with which 1 and 2 react, even in the presence of water, presents new opportunities for expanding TosMIC chemistry for the synthesis of imidazoles from small molecule building blocks with multiple functionalities. Although published procedures employing substituted TosMIC reagents imply the need for strictly anhydrous conditions, , the results shown in Scheme belie that notion. Described herein are the results of an investigation which has culminated in the development of processes for the efficient synthesis of functionally rich 1,4- and 4,5-disubstituted imidazoles, as well as 1,4,5-trisubstituted imidazoles, under partially aqueous conditions.…”
This article describes efficient and mild protocols for preparing polysubstituted imidazoles in a single pot from aryl-substituted tosylmethyl isocyanide (TosMIC) reagents and imines generated in situ. Traditional imine-forming reactions employing virtually any aldehyde and amine followed by addition of the TosMIC reagent delivers 1,4,5-trisubstituted imidazoles with predictable regiochemistry. Employing chiral amines and aldehydes, particularly those derived from alpha-amino acids, affords imidazoles with asymmetric centers appended to N-1 or C-5 with excellent retention of chiral purity. 1,4-Disubstituted imidazoles are also readily prepared by a simple variant of the above procedure. Selecting glyoxylic acid as the aldehyde component of this procedure leads to intermediates such as 48, which readily undergo decarboxylation and elimination of the tosyl moiety to deliver 1,4-disubstituted imidazoles in high yields. Alternatively, using NH(4)OH as the amine component in conjunction with a variety of aldehydes delivers 4, 5-disubstituted imidazoles in moderate to good yields in a single pot while avoiding the need for protecting groups. Finally, the facile preparation of mono- and disubstituted oxazoles from these TosMIC reagents and aldehydes is described.
“…The facility with which 1 and 2 react, even in the presence of water, presents new opportunities for expanding TosMIC chemistry for the synthesis of imidazoles from small molecule building blocks with multiple functionalities. Although published procedures employing substituted TosMIC reagents imply the need for strictly anhydrous conditions, , the results shown in Scheme belie that notion. Described herein are the results of an investigation which has culminated in the development of processes for the efficient synthesis of functionally rich 1,4- and 4,5-disubstituted imidazoles, as well as 1,4,5-trisubstituted imidazoles, under partially aqueous conditions.…”
This article describes efficient and mild protocols for preparing polysubstituted imidazoles in a single pot from aryl-substituted tosylmethyl isocyanide (TosMIC) reagents and imines generated in situ. Traditional imine-forming reactions employing virtually any aldehyde and amine followed by addition of the TosMIC reagent delivers 1,4,5-trisubstituted imidazoles with predictable regiochemistry. Employing chiral amines and aldehydes, particularly those derived from alpha-amino acids, affords imidazoles with asymmetric centers appended to N-1 or C-5 with excellent retention of chiral purity. 1,4-Disubstituted imidazoles are also readily prepared by a simple variant of the above procedure. Selecting glyoxylic acid as the aldehyde component of this procedure leads to intermediates such as 48, which readily undergo decarboxylation and elimination of the tosyl moiety to deliver 1,4-disubstituted imidazoles in high yields. Alternatively, using NH(4)OH as the amine component in conjunction with a variety of aldehydes delivers 4, 5-disubstituted imidazoles in moderate to good yields in a single pot while avoiding the need for protecting groups. Finally, the facile preparation of mono- and disubstituted oxazoles from these TosMIC reagents and aldehydes is described.
“…The obtained sulfones 14 are mostly stable solids that often precipitate from the reaction mixture and are easily recovered by a simple filtration. The classical procedure usually gives poor results when formamide is used to prepare sulfones 14 ; , however, a slight modification in the reaction conditions allows a proper preparation of these amido derivatives . Alternatively, α-amido sulfones 16 can be obtained by oxidation of the corresponding sulfides 15 using hydrogen peroxide or MCPBA (Scheme ). − 4 …”
“…Aryl derivatives 17 (R 1 ¼ aryl) have been prepared by Mannich reaction followed by dehydration (Scheme 5) [11,12]. A large number of monosubstituted alkenyl and long chain alkyl substituted TosMIC derivatives have been prepared according to Scheme 4 by various groups of workers for the synthesis of intermediates used in natural product synthesis [13][14][15][16][17][18][19][20][21][22].…”
Section: (R=alkyl)mentioning
confidence: 99%
“…Unusual macrocycles containing oxazole rings 51 and 52 have been synthesized from TosMIC derivatives 49 and 50 by reaction with m-phenylene dialdehyde 48 (Scheme 23) [12,37]. The 5-oxazole derivative 54, a potent 5-HT 1 A agonist, has been synthesized by reaction of carboxaldehyde 53 with TosMIC in the presence of NaOMe and MeOH (Scheme 24) [38].…”
Section: Oxazolesmentioning
confidence: 99%
“…The isomeric 2H-pyrrolo [3,4-b] [1,5]benzothiazepine derivative 221 has been synthesized from 2-nitrothiophenol according to Scheme 83 [77] 2.11. Benzazocines 1,2-Dibromomethyl benzene and TosMIC (two molecules) react together in the presence of base to form the product 222 which undergoes a base-induced intramolecular cyclization to form the benzazocine derivative 223 (Scheme 84) [12]. …”
TosMIC, a versatile synthon in organic chemistry, has been extensively used for the synthesis of a wide variety of small, medium and large ring heterocycles. It has immense implications in the synthesis of nitriles, aldehydes, ketones, alkanes, cyclophanes and large number of natural products. Several drug intermediates and pharmacologically active compounds have been synthesized from TosMIC. In addition, chiral TosMIC analogs have been synthesized and employed for synthesis of optically active compounds.
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