Sulfonyl isocyanate, reactions with amines

Isomannide (80) was the core for a hexahydrofurofuran library." Primary amines were loaded onto solid-support by reductive amination and acylated with bromoacetic acid to give bromides 79 (Scheme 7.16). Alkylation of bromides 79 on solid-support with isomannide (80) gave the solid-supported alcohols 81. A Mitsunobu reaction with phthalimide (82) proceeded to furnish amines 83 in excellent yield and purity after removal of the protecting group." " Support-bound primary amines 83 were converted to secondary amines by stepwise imine formation with aldehydes 84 and reduction with sodium borohydride." The hindered secondary amines 85 were acylated with acid chlorides, sulfonyl chlorides, isocyanates, and isothiocyanates to yield 87 after cleavage from solid-support. 

The acylation with acid chloride and the urea formation with isocyanate of intermediate resin 16 afforded other substituent groups onto 4-aminothiazole. Under microwave (MW) irradiation reaction with isocyanate and acylation reaction with acid chloride, R -substituted thiazole resin 19 was obtained. Following conversion of sulfonyl resin 19 to sulfonyl resin 20 (mCPBA/CH2Cl2), substitution reactions promoted by treatment with appropriate amines (R R" N diversity elements) furnished the 2,4,5-trisubstituted thiazoles 2 (29 examples 36-25% isolated yields from Merrifield resin 1, >95% purities, Table 10.1). 

Williams and coworkers used a [G4]-PAMAM dendrimer as a scavenger in the reactions of an arylpiperazine with slight excesses of three different electrophiles (an isocyanate, a sulfonyl chloride, and a benzyl halide) [62]. After TLC had indicated that all amine substrate had reacted the dendritic scavenger was added. Solvent removal, adding of chloroform, and filtration of the unsoluble dendrimer afforded the products in high yields (87-99%) and purities (>95%, HPLC). 

Reactions between an excess of acylating agents (isocyanates, acyl chlorides, chloroformates, or sulfonyl chlorides) with secondary amines were performed in the presence of the resin bound tertiary amine 2 (see Figure 7.16). After reaction completion (16 h, DCM, room temperature) a resin bound... 

HN J From chloromethyl polystyrene by treatment with tris(2-ami noethyl )amine in DMF. Ti Scavengers to remove excesses of isocyanates, carboxylic acid chlorides or sulfonyl chlorides from reaction mixtures. - - ... 

Reagents of by-products can also be trapped by covalent binding to a polymer. Kaldor et reported the use of aminomethyl polystyrene for the extraction of isocyanates, acid chlorides or sulfonyl chlorides from reaction mixtures (Scheme 3.4.3, entry a). Similarly, amines were trapped with polymer-supported isocyanates, acid chlorides or aldehydes (Scheme 3.4.3, entry b). 

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