Amino alcohols cyclization with phosgene

Amino alcohols 127 are readily available from o-aminothiophenols and oxirane. They were further cyclized with phosgene or triphosgene to afford dibenzo[<7,g][l,6,3]oxathiazocin-6(777)-ones 128 in moderate to good yields (Scheme 32 <1997USP5621153>). 

Isothioureas can be prepared on insoluble supports by S-alkylation or S-arylation of thioureas (Entry 7, Table 14.6). Further methods for the preparation of isothioureas on insoluble supports include the N-alkylation of polystyrene-bound, A/,/V -di(alkoxy-carbonyl)isothioureas with aliphatic alcohols by Mitsunobu reaction (Entry 7, Table 14.6) and the addition of thiols to resin-bound carbodiimides [7]. Resin-bound dithio-carbamates, which can easily be prepared from Merrifield resin, carbon disulfide, and amines [76], react with phosgene to yield chlorothioformamidines, which can be converted into isothioureas by treatment with amines (Entry 8, Table 14.6). The conversion of support-bound a-amino acids into thioureas can be accompanied by the release of thiohydantoins into solution (see Section 15.9). The rate of this cyclization depends, however, on the type of linker used and on the nucleophilicity of the intermediate thiourea. 

To build up the desired cyclic key precursors, containing an amide bond as an anchor to connect the triazole moiety, different strategies can be pursued. Cyclization of y-amino acids directly yields pyrroli-dones, whereas P-amino alcohols allow access to two different chiral bicyclic frameworks. They can form either oxazolidin-2-ones (Enders and Kallfass 2001) or morpholinones upon treatment with phosgene or chloro acetylchloride, respectively (Scheme 3). 

Reaction of phosgene with the following two amino alcohols at < -30 C in CHjClj gives the corresponding iV-carbamoyl chlorides cyclization was induced by treatment with NEtj to give bicyclic urethanes [870] ... 

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