Samarium Diiodide Promoted Reduction of 3,6‐Dihydro‐2H‐1,2‐oxazines: Competition of 1,4‐Amino Alcohol Formation and Ring Contraction to Pyrrole Derivatives

Abstract

An approach to enantiopure 1,4‐amino alcohols of type 4 by samarium diiodide mediated N–O cleavage of 3,6‐dihydro‐2H‐1,2‐oxazines 3 is presented. In several cases we observed the formation of 3‐methoxypyrrole derivatives 5 as byproducts in significant amounts. For 1,2‐oxazine derivative syn‐3a, up to 27 % of pyrrole 5a was isolated. The examples presented show a strong dependence of the chemoselectivity on the structure of the precursor 1,2‐oxazines. The formation of pyrroles 5 as side‐products is rationalized by a competitive intramolecular hydrogen shift of the initially formed ring cleavage intermediate B to C and subsequent cyclization of aldehyde E to afford F. This pathway can be disfavoured when a higher excess of samarium diiodide was employed, which generally provided the 1,4‐amino alcohols 4 in good yields.

Pyrrole: a resourceful small molecule in key medicinal hetero-aromatics

“…Water was used as a solvent and the reaction proceeded under ultrasonic irradiations. 41 During samarium di-iodide mediated N-O cleavage of 3,6-dihydro-2H,1,2-oxazine 52; an enantiopure 1,4amino alcohol 53 and 3-methoxypyrrole derivative 54 were prepared in signicant amounts 42 as shown in Scheme 10. A sequential multicomponent process was designed to prepare the polysubstituted functionalized pyrroles 55 that involved the high-speed vibration milling of ketones with N-iodosuccinimide and p-toluene sulphonic acid, followed by the addition of mixture of primary amines, b-dicarbonyl compounds, cerium(IV) ammonium nitrate and silver nitrate.…”

[3+3]-Annulation of Cyclic Nitronates with Vinyl Diazoacetates: Diastereoselective Synthesis of Partially Saturated [1,2]Oxazino[2,3-b][1,2]oxazines and Their Base-Promoted Ring Contraction to Pyrrolo[1,2-b][1,2]oxazine Derivatives

“…However, none of the desired transformation was observed, albeit ring contraction occurred providing pyrrolo[1,2- b ]oxazine derivative 4b . This process has some precedents in the literature [ 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ], with the closest analogue observed by Kerr et al for non-annulated oxazines under the treatment with DBU in MeCN [ 67 ]. The proposed mechanism starts with the deprotonation at C(2), which is facilitated by the conjugation of the formed anion with C=C–CO 2 moiety in D ( Scheme 4 ).…”

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

“…As a milder alternative, samarium diiodide was examined for the N–O bond cleavage [ 40 – 45 ]. With this selective reagent a TBS protected aminopyran dimer 23 was expected that should be well soluble in organic solvents and therefore more suitable for subsequent transformations ( Scheme 10 ).…”