Dihydro-1,3-oxazines synthesis

Domling, A., The discovery of new isocyanide-based multi-component reactions, Curr. Opin. Chem. Biol, 2000, 4, 318-323 Domling A., and Ugi I.K., A new 5,6-dihydro 211 1,3-oxazine synthesis via Asigner-type condensation, Tetrahedron, 1993, 49, 9495-9500. 

Another type of nitroso dienophile that has found use in organic synthesis bears an a-chloro substituent. Such a-chloronitroso compounds react with dienes to give the usual dihydro-oxazine product, however, in the presence of an alcoholic solvent, this cycloadduct reacts further and the product actually isolated is the A-unsubstituted dihydro-oxazine (3.32). Hence the use of a-chloronitroso dienophiles gives the product formed, in effect, by addition of HN=0 to the diene. This has been exploited by a number of research groups, an example of which, towards the natural compound conduramine FI, is illustrated in Scheme 3.33. 

A large number of 1-oxa-l-dethiacephalosporins have been prepared from a readily available penicillin-derived azetidinone. The central feature of the synthesis is the use of an intramolecular Wittig reaction, as shown in Scheme 140, to form the dihydro-oxazine ring. ... 

Oxazines. The synthetic utility of dihydro-1,3-oxazines ° has been considerably extended by Meyers. The reactivity of the double bond in dihydro-oxazines is enhanced on quaternization with methyl iodide the resulting salt readily adds a range of organometallic reagents, affording the versatile ketone synthesis summarized in Scheme 62. 

The potential of dihydro-oxazines is displayed to advantage in a high-yield synthesis of the male bollworm moth pheromone, tra/w-l-acetoxy-10-n-propyltrideca-5,9-diene. Alkylation of anions from dihydro-oxazines with a,o)-dihalogenoalkanes and subsequent elaboration of the terminal halide provides a route to variously functionalized aldehydes (Scheme 63). 

The Kouklovsky/Vincent and co-workers formal synthesis of ( )-porantheridine 197 (discovered from the Australian bush Poranthera corymbosa) is complementary to the work of Kibayashi (Scheme 41.41). ° The treatment of hydroxamic acid 192 with sodium periodate in the presence of cyclopentadiene 33 in methanol and water at 0°C delivered the bicyclic 3,6-dihydro-oxazine 193 in 61% yield. Ring-rearrangement metathesis (ring opening/ring... 

Dibenz[h,e]azepine-6,11-diones ent-Morphinan nomenclature, 1, 29 Morphinan, 1,2,3,4-tetrahydro-nomenclature, 1, 29 14-a-Morphinan, N-methyl-synthesis, 1, 480 Morphinans nomenclature, 1, 29 as pharmaceuticals, 1, 148 synthesis, 2, 377 Morphine, 2, 512 as analgesic, 1, 167 as metabolite of normorphine, 1, 235 as pharmaceutical, 1, 146, 147, 148 synthesis, 1, 480 Morphine alkaloids structure, 4, 534 Morphin-7-en nomenclature, 1, 29 Morphinone, dihydro-as pharmaceutical, 1, 147 Morpholine — see also 1,4-Oxazine, tetrahydrocarcinogenicity, 1, 229 corrosion inhibitor, 1, 409 metabolism, 1, 226 nomenclature, 3, 996 structure, 2, 5 synthesis, 2, 89 Morpholine, 4-aciyloyl-polymers, 1, 291 Morpholine, alkenyl-polymers, 1, 291... 

H-1,2-Oxazine, 3,6-dihydro-6-(2-pyridyl)-mass spectra, 2, 529 2H-1,2-Oxazine, tetrahydro-synthesis, 2, 92 4H-l,2-Oxazine, 5,6-dihydro-pyrolysis, 3, 999 synthesis, 3, 1017 tautomerism, 3, 999 4H-1,2-Oxazine, 5,6-dihydro-3-methyl-metallation, 1, 484 4H-l,2-Oxazine, 5,6-dihydro-3-nitro-reactions, 3, 1000 6H-l,2-Oxazine, 3,5-diphenyl-stability, 3, 997 synthesis, 3, 1014... 

H-l,2-Oxazine-3-carboxylic acid, 5,6-dihydro-synthesis, 1, 484 Oxazine-4,6-dione, 2-methylene-synthesis, 3, 1031... 

Alkylation of Dihydro-1,3-Oxazine The Meyers Synthesis of Aldehydes, Ketones, and Carboxylic Acids... 

A synthesis of aldehydes developed by Meyers begins with the commercially available dihydro-1,3-oxazine derivatives 132 (A = H, Ph, or COOEt). Though the ions (133) prepared from 132 are ambident, they are regioselectively alkylated at... 

Synthesis of 5,6-Dihydro-4H-Oxazines Containing Functionalized Substituents at the C-3 Atom Unlike BENAs, six-membered cyclic nitroso acetals do not form quaternary ammonium salts in the reactions with StX/Nu. ... 

Table 3.36 The synthesis of 3-halomethyl substituted 5,6-dihydro-4//-oxazines (517).

In some cases, silylation of AN and their derivatives produces nitroso acetals containing the N -siloxy fragment or cyclic ethers of oximes (predominantly substituted 5.6-dihydro-4f/-oxazines). To use these products in strategies for synthesis, it is worthwhile to develop convenient procedures for selective reductions of the above derivatives to the corresponding amines. 

Reduction of the Oximino Fragment in Substituted 5,6-Dihydro-4H-Oxazines Catalytic hydrogenation of substituted dihydro-477-oxazines (552), as well as their reduction with sodium cyanoborohydride (553), were studied in sufficient detail and were used in several total syntheses. However, the use of silylation of six-membered cyclic nitronates enables the synthesis of previously unknown dihydrooxazines containing functionalized substituents at the C-3 and C-4 atoms from easily available precursors. 

An intermediate 5-hydroxy-5,6-dihydro-2/7-pyrrolo[l,2- ][l,2]oxazin-7(4a//)-one 142 has been described in the total synthesis of (—)-loline, a pyrrolizidine alkaloid extracted from rye grass Lolium cuneatum. The key step of the synthesis was an intramolecular cycloaddition of acylnitrosodienes (obtained by in situ oxidation of the corresponding hydroxamic acids 143). This reaction generated predominantly the rro/o-stereoisomer that was further cleaved at the N-O bond with Na(Hg) and further elaborated in several steps to reach the target compound (Scheme 19) <2001J(P 1)1831 >. 

Tetramethyl-5,6-dihydro-1,3 (4H) -oxazine, for synthesis of substituted acetaldehydes, 51, 30 ... 

Synthesis of 2,4-Disubstituted-3,4-Dihydro-2//-Naphth[2,l-e][l,3]Oxazines Conclusion... 

Substituted amino naphthols were synthesized with reactions of 1-naphthols and the appropriate aldehydes. Some new 2,4-disubstituted-3,4-dihydro-2/f-naphth [i,2-e][i,i]oxazines that are expected to show biological activities were obtained by the ring-closure reactions with these aminonaphthols and various aldehydes. In addition, substituted-1,3-amino-hydroxy compounds, 2, can be used in chiral ligands synthesis. 

Information concerning the spectral characteristics of 1,3-oxazinium derivatives discussed above is scant. Systematic investigations have not been carried out. In work devoted to the synthesis of 5,6-dihydro-l,3-oxazinium, 1,3-oxazinium, and benzo-l,3-oxazinium salts, these products underwent deprotonation without identification or even isolation. Such articles contain only the spectra of the corresponding uncharged 1,3-oxazines. A few recent publications describe these salts as individual compounds. 

Perhydro derivatives of pyrido[l,2-6][l,2]oxazines are frequently applied in the total synthesis of various alkaloids to control the stereochemistry, and 4-(substituted amino)-5-fluoro-7-oxo derivatives of 3,7-dihydro-2//-pyrido[3,2,l-f7][2,l]benzoxazine- and l,2,3,7-tetrahydropyrido[3,2,l-//]cin-noline-8-carboxylic acids are considered as a subfamily of the third generation of antibacterial quinolones. 

In comparison with the 1,3-oxazines, much less attention has been paid to the synthesis of cycloalkane-fused 1,3-thiazines. Only a few 2-thioxo-, 2-imino-, and 2,4-dioxotetrahydro derivatives are known. The most versatile method for the synthesis of the dihydro derivatives is cycloaddition. 

The cyclocondensation of l,3-amino alcohols with carboxylic acid derivatives is a method often applied for the synthesis of 5,6-dihydro-4/7-l,3-oxazines <1996CHEC-II(6)301 >. Ebsorb-4, a weakly acidic zeolite-type adsorbent with 4 A pore size, proved an efficient catalyst of the cyclization of benzoic acid and 3-aminopropanol <2002TL3985>. In the presence of zinc chloride as a catalyst, the expulsion of ammonia drove the reactions of 3-aminopropanol with nitriles to completion, affording 2-substituted 5,6-dihydro-47f-l,3-oxazines in good yields... 

The synthesis of l,3-oxazin-4-ones of type 464 is the first example of the formation of a C-O bond in the course of the Norrish-Yang reaction. Upon treatment with 1-hydroxy-l-phenyl-A -iodanyl mesylate, /3-keto amide 460 was converted to the corresponding a-mesyloxy-/3-keto amide 461 in excellent yield. On ultraviolet (UV) irradiation (A>300nm) of 461, 5-hydrogen transfer to the excited carbonyl group occurred and the diradical 462 thus formed underwent MsOH elimination to enolate diradical 463, cyclization of which resulted in formation of 3-methyl-6-phenyl-3,4-dihydro-277-l,3-oxazin-4-one 464 (Scheme 89) <2001S1258>. 

For the enantioselective synthesis of a-alkyl-a-phenylglycines the enolates 2, derived from (S)-3,6-dihydro-3-phenyl-2i/-l,4-oxazin-2-ones, 1, were alkylated91. (S)-l is available from an (S)-a-hydroxy acid (R1 = i-Pr, C6H5, Bn) and racemic phenylglycine in five steps. The yields of the alkylation step are around 90%, but the diastereoselectivity is strongly dependent on R1. 

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