1.3- Oxazines from thioureas

Various types of six-membered rings are formed from thioureas. Elimination of isothiocyanate from the butadienylthiourea ArNHC(S)NH(CH=CH)2CHO yields pyridine, whereas the oxazine (48) arises from ketone (47). The... 

Thioxo derivatives 105 (R = H, Me) were prepared through the thermal cyclization of thioureas 104, which are readily available from the corresponding amino alcohols with phenyl isothiocyanate. The thermal cycliza-tions resulted in l,3-oxazine-2-thiones by loss of aniline, but the yields were only moderate (R = H 43% R = Me 31%) (880PP73). 

Aminopropanols, when reacted with cyanogen bromide, also afford 2-amino-(or imino)-dihydro-1,3-oxazines (Scheme 90) (64ZOB3427), and related thiazines are formed when allylic isothiouronium salts (207) are cyclized with trifluoroacetic acid and stannic chloride. The necessary starting materials are synthesized from aldehydes or ketones by the action of vinylmagnesium chloride and subsequent treatment of the product allyl alcohols (206) first with hydrogen chloride and then with a thiourea (Scheme 91) (77JHC717). 

A closely related synthesis of tricyclic oxazines and oxazolidines was reported shortly afterward by Ye s group when the internal nucleophile is a hydroxyl function from a benzyhc alcohol or a phenol, respectively [18]. Enamides have also been proposed by Wang and collaborators [19] as functionalized pronucleophiles in a similar organocascade with unsaturated aldehydes promoted by diphenyl prolinol silyl ether in the presence of phenylacetic acid to give cychc hemiaminals. Recently, we proposed the first example of activation of 7V-tosyl-l,3-ketoamides under thiourea-based bifimctional catalysis for an enantioselective domino Michael/spirolactamiza-tion sequence leading to chiral scaffolds of high synthetic interest [20]. 

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