Substituted 1,4-Benzoxazepines, 1,5-Benzoxazocines, and N- and S-Variants

Abstract

Nucleophilic cleavage of enantiomerically pure 1,2-cyclic sulfamidates with phenol, aniline, and thiophenol nucleophiles, followed by a Mitsunobu reaction, including use of a o-quinomethide variant of this process, provides an entry to substituted 1,4-tetrahydrobenzoxazepines, benzothiazepines, and benzodiazepines. Application of this methodology to 1,3-cyclic sulfamidates affords a parallel entry to the analogous substituted 1,5-benzoxazocines and 1,5-benzodiazocines.

Importance and synthesis of benzannulated medium-sized and macrocyclic rings (BMRs)

“…For example, the bridged benzannulated macrocycle 200 was synthesized starting from amino acid 198 (Scheme 7a) 121 while the benzannulated medium-ring ether (48) was prepared via nucleophilic cleavage of enantiomerically pure 1,2-cyclic sulfamidate 201 with phenol derivative 202, followed by Mitsunobu reaction of 203, which led to the formation of scaffold 204 in 30% overall yield, as shown in Scheme 7b. 122 Another variant of the Mitsunobu reaction was reported to affect the closure of a 13-membered lactone in the presence of supported triphenylphosphine in low yield (10%) but was recently more successful in the formal synthesis of salicylihalamides (206, Scheme 7c). 119,123 The intramolecular Mitsunobu cyclization between the sulphonamide and benzylic hydroxyl in 212 (derived from amino acid 207 through a series of reactions, as depicted in Scheme 7d) furnished enantiomerically pure benzannulated mediumring thio-ethers of the type 213 in 69% yield, as depicted in Scheme 7d.…”

Chemoselectivity Control in the Reactions of 1,2‐Cyclic Sulfamidates with Amines

“…We started our study with propylamine as a representative primary amine because it is readily available and liquid at room temperature. Following a protocol similar to that described for other reactions of sulfamidates with various nucleophiles,9a we carried out the reaction of sulfamidate ( R )‐ 1 with propylamine (4.0 equiv) in the presence of Cs 2 CO 3 in THF as solvent at room temperature (Table 1, entry 1). After 8 h of reaction, we obtained a 42 % yield of compound ( R )‐ 2 derived from N‐deprotection of the sulfamidate (cleavage of methyl carbamate).…”

Multicomponent Synthesis of Chiral Sulfinimines

“…Template 3 (Scheme ) is prepared in three steps from L ‐phenylalanine or in two steps from L ‐phenylalaninol. Since our initial preparation of 3 its formation as a diastereomeric mixture has been published by Gallagher and Rujirawanich8 using thionyl chloride and pyridine. The issue of the formation of the diastereomeric mixture was overcome by the avoidance of an aqueous workup, which we found gave rise to the partial epimerization of oxathiazolidine‐ S ‐oxide 3 .…”