117341-61-4Relevant academic research and scientific papers
Model Studies of the Reduction of 3-Phenyl-6H-1,2-oxazines, Chemo- and Stereoselectivity: Synthesis of Amino Alcohols, Amino Acids, and Related Compounds
Zimmer, Reinhold,Hoffmann, Matthias,Reissig, Hans-Ulrich
, p. 2243 - 2248 (2007/10/02)
While palladium-catalyzed hydrogenation of 3-phenyl-6H-1,2-oxazine 1 produces primary amine 5 in a nitrogen-transposition reaction, the reductions of the related 1,2-oxazines 2, 10, and the 1,2-oxazin-6-one 3 afford the expected amino alcohols 4, 11, and the γ-amino acid 6, respectively, with low diastereoselectivities.In the presence of acetic acid 3 is reductively converted into γ-keto carboxylic acid 9 and 1 into the γ-lactam derivative 12 probably by a ring contraction to a nitrone intermediate.Raney nickel as the catalyst is able to transform 1,2-oxazine 7 bearing an exo-methylene unit into 3,4-dihydro-2H-pyrrole 13.The reaction of 6H-1,2-oxazine 1 with aluminium amalgam produces pyrrole 14 in moderate yield.Treatment of 1 with sodium in 2-propanol brings about its transformation into pyrrolidine derivative 15 together with pyrrole 14 and amino alcohol 4 as minor products.The chemoselectivity and stereoselectivity of these reductions are discussed including mechanistic proposals for the multistep processes involved. Key Words: 1,2-Oxazines / Hydrogenation, catalytic / Amino alcohols / γ-Amino acids / Pyrroles / γ-Lactams
Synthesis of 6H-1,2-Oxazines by Hetero Diels-Alder Reactions of Nitroso Alkenes towards Methoxyallenes
Zimmer, Reinhold,Reissig, Hans-Ulrich
, p. 553 - 562 (2007/10/02)
Regioselective hetero Diels-Alder reactions of in-situ generated nitroso alkenes 2-4 with methoxyallene derivatives 1 provide 4H-1,2-oxazines 5-7 with an exo methylene group at C-5.These primary cycloadducts are smoothly transformed into conjugated 6H-1,2
Deprotonation of 5,6-Dihydro-5-methylene-4H-1,2-oxazines and Regioselective Reactions with Electrophiles
Unger, Clemens,Zimmer, Reinhold,Reissig, Hans-Ulrich,Wuerthwein, Ernst-Ulrich
, p. 2279 - 2287 (2007/10/02)
5,6-Dihydro-5-methylene-4H-1,2-oxazine 1 is smoothly converted by n-butyllithium into 1-Li which reacts with electrophiles such as D2O, carbonyl compounds, dimethylsulfide, or an azo diester to give the γ-adducts 4a-4f.On the other hand, alkylation of 1-Li occurs exclusively at C-4 of the heterocycle and provides the α-adducts 3g and 3h.These reactions require the activation of 1-Li by tetramethylethylenediamine.Treatment with allyl bromide and methyl acrylate affords mixtures of regioisomers 3 and 4. 1,2-Oxazine 5 with a conjugated C=C bond is less acidic than 1 but is also converted into 1-Li, whilst compound 6, lacking the 6-methoxy group, is not deprotonated under standard conditions.The dianion of 1,2-oxazine 7 is generated by employing an excess of n-butyllithium.This dianion displays a similar regiochemical behavior as 1-Li.Deuterium is exclusively incorporated into the γ-position to give product 8, while methylation occurs at C-4 to produce 9. 1,2-Oxazine 3g with an additional 4-methyl group can also be metalated and affords γ-adducts 10 and 11 upon reaction with D2O or acetone.Treatment with methyl iodide give a 3:1 mixture of regioisomers 12 and 13.Deuteration of 1,2-oxazines 14 and 16 bearing a 3-CF3 or 3-CO2Et substituent requires more severe deprotonation conditions to provide the γ-adducts 15 and 17 in moderate yields.MNDO calculations of neutral 1,2-oxazines, the corresponding carbanions, and the lithium compounds allow an insight into the structure and charge distribution of these species, and also an estimation of the relative acidities.The regioselectivity of reactions of 1-Li is discussed on the basis of these semiempirical calculations and comparison with related ambident nucleophiles.Key Words: 1,2-Oxazines, lithiated / Deprotonation / Alkylation / Deuteration / Regioselectivity / Calculations, MNDO
