Divergent Reactions of 2‐Aminophenol with α‐Bromoacetate: Asymmetric Synthesis of Two Regioisomeric 1,4‐Benzoxazinones

Abstract

2-Aminophenol displays a diverse pattern of reactivity in the substitution reaction of α-bromoacetate. The substitution under neutral or basic conditions results in the formation of 1,4-benzoxazinones, whereas Lewis acid-promoted substitution leads to Friedel-Crafts alkylation of 2-aminophenol. Asymmetric synthesis of two regioisomeric 1,4-benzoxazinones is accomplished from the nucleophilic substitution of highly diastereoenriched α-aryl-α-bromoacetates with N-alkyl-2-aminophenols under varied reaction conditions.

Synthesis of (1,4-benzoxazinones-3-yl)malonate derivatives via cross-dehydrogenative-coupling reactions under ball-milling conditions

“…With FeCl3 (entry 4), various copper salts (entries 5-10) or CoCl2.6H2O (entry 11) the yield dropped partially. Similarly, no improvement was observed by replacing DDQ with other oxidants (entries [12][13][14][15][16][17][18][19].…”

“…[13][14][15][16] Therefore, the development of new methods for the synthesis and derivatization of 1,4benzoxazinones is of continuous interest. [17][18][19][20] Iron is one of the most abundant elements on Earth and iron salts act as catalyst for several chemical transformations, 21 while they are inexpensive and nonharmful to humans and the environment. 22,23 These features make various types of iron catalysts very popular in organic synthesis and have resulted in many applications in recent decades.…”