Regiocontrolled Synthesis of 4‐Halo‐5,6‐Dihydro‐4H‐1,2‐Oxazines; A Novel Route for α‐Fluorovinyl Ketones

Regiocontrolled deprotonation (e.g. lithiation) of 3‐methyl‐4‐H‐5,6‐dihydro‐1,2‐oxazine 1 is achieved at −65°C. The lithiated compound reacts cleanly with the halogens Cl₂, Br₂ and I₂ at low temperatures (−65°C) to give the corresponding 4‐halo derivatives. Reaction of the 4‐iodo compound 2a with KF in diethyleneglycol gives the elimination product 4 whereas the bromo compound 2b reacts under substitution to the 4‐fluoro derivatives 5. The fluorooxazine derivatives 8a‐c were converted to the αfluoroenones 11 a‐c via the oxoiminium salts 10a‐c. The U.V. and ¹HNMR of the novel series of halides 2a‐c and 5 were studied.