Reactivity in [4+2] cycloadditions of new 4-trifluoromethyl-1,3-oxazin-6-ones: Access to functionalized 2-trifluoromethyl pyridines

Abstract

Recently discovered 4‐trifluoromethyl‐1,3‐oxazin‐6‐ones react with electron‐poor dienophiles as 2‐aza‐1,3‐dienes in Diels‐Alder cycloadditions to give new 2‐trifluoromethyl pyridines (3a–d, 4a–c). Regioselectivity is excellent in the case of unsymmetrical dienophiles. These new pyridines permit further useful transformations.

Diels–Alder reactions of trifluoromethyl alkenes with 5-ethoxyoxazoles: synthesis of trifluoromethylated pyridine derivatives

“…Viehe and co-workers [9] prepared a series of 2-trifluoromethylpyridine derivatives by performing cycloaddition reactions between trifluoromethyl oxazinone and a variety of electronpoor alkynes whilst Schlosser reported that 1-ethoxy-3-trifluoromethyl-1,3-butadiene [10] underwent cycloaddition with a range of imines to give various trifluoromethylpyridine products.…”

1,2,4‐Triazine vs. 1,3‐ and 1,4‐Oxazinones in Normal‐ and Inverse‐Electron‐Demand Hetero‐Diels–Alder Reactions: Establishing a Status Quo by Computational Analysis

“…Steglich [12] has suggested that a lower degree of reactivity and regioselectivity can be expected for 1,4-oxazin-2ones 3 as compared to 1,3-oxazin-6-ones 2, and Boger [21] suggests the reactivity of similar substituted 1,3-oxazin-6ones 2 is comparable to 1,2,4-triazines 1. A further example that adds confusion to the situation is that 1,3-oxazin-6ones 2 react with both electron-poor [19] and -rich [20,21] acetylenes to afford pyridines, depending on the substitu-in the unsubstituted cases 1,2,4-triazine is less reactive in comparison to 1,3-oxazin-6-one and 1,4-oxazin-2-one for both reaction modes, whereas the cycloaddition regioselectivities depend largely on the diene. For example, 1,3-oxazin-6-one leads to kinetic meta isomers, in comparison to 1,2,4triazine and 1,4-oxazin-2-one, which give rise to para isomers.…”