Aldehydes from dihydro-1,3-oxazines

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). 

ALDEHYDES FROM ALLYLIC ALCOHOLS AND PHENYLPALLADIUM ACETATE 2-METHYL- 3-PHENYLPROPIONAL-DEHYDE, 51, 17 ALDEHYDES FROM AROMATIC NITRILES p-FORMYLBENZENE-SULFONAMIDE, 51, 20 ALDEHYDES FROM 2-BENZYL-4,4,6-TRIMETHYL—5,6-DIHYDRO-l, 3-(4H)-OXAZINE 1-PHENYLCYCLO-PENTANECARBOXYALDEHYDE, 51,... 

ALDEHYDES FROM 2-BENZYL-4,4,6-TRIMETHYL-5,6-DIHYDRO-l,3(4H)-OXAZINE ... 

Politzer, I.R., and Meyers, A.L, Aldehydes from 2-benzyl-4,4,6-trimethyl-5,6-dihydro-l,3(4/7)-oxazine. 1-Phenylcyclopentanecarboxaldehyde, Org. Synth. Coll., VI, 905, 1988. 

The anions derived from dihydro-1,3-oxazines have been nicely exploited as reagents to effect the two-carbon homologation of carbonyl compounds to provide a,3-unsaturated aldehydes, ketones and carboxylic acid derivatives. " For example, metallation of (77) followed by reaction with a wide variety of aldehydes and ketones provides adducts (78 Scheme 29 Although attempts to purify these adducts have been unsuccessful owing to facile retroaldolization, sequential reduction of (78) with sodium... 

Sodium tetrahydridoboratelhydrogen chloride Aldehydes from 5,6-dihydro-4H-l,3-oxazines C... 

Sodium tetrahydridoborate hydrogen chloride Aldehydes from 5,6-dihydro-4H-l,3-oxazines s. 23, 56 s. a. J. Org. Chem. 38, 36 (1973)... 

Metalloenamines derived from dihydro-1,3-oxazines are key intermediates in an alkylation reaction leading to aldehydes. 

Silver carbonate-on-Gelite has been recommended for the oxidation of alcohols to aldehydes and ketones. It does not attack hindered hydroxyl groups Prim, amines can be converted to ketones under mild conditions through prototropic isomerization of certain Schiff bases A variety of aldehydes, including deu-terio-, a, -ethylene-, and cycloalkane-aldehydes have been obtained in a novel manner from dihydro-1,3-oxazines Non-con-... 

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... 

Aldehydes, a-phenyl-, from 2-benzy1-4,4,6-trimethyl-5,6-dihydro-1, 3(4H)-oxazine,... 

This technique may also be modified to prepare acetaldehyde derivatives by use of 2,4,4,6-tetramethyl-5,6-dihydro-l,3(4H)-oxazine1 2 3 4 5 6 7 and 2-carboethoxy acetaldehydes using 2-(carbo-ethoxymethyl)-4,4,6-trimethyl-5,6-dihydro-l,3(4H)-oxazine.3 Functionalized aldehydes and dialdehydes may also be obtained by suitable modification.8 Generally, the intermediates can be used without purification and the overall yields of the aldehydes range from 50-70%. 

In the condensation of /3-hydroxy aldehydes 303 with A -sulfonyl aliphatic aldimines 304 (which could also be prepared in situ from the aliphatic aldehyde and A -sulfinyl /i-toluenesulfonamide), 2,5,6-trisubstituted 3,6-dihydro-277-1,3-oxazines 306 were formed as single /ra r-stereoisomers (Scheme 57). No oxazine formation was observed in the... 

The benzoylphenylketene generated from 321 displayed a pronounced tendency to form chemospecific [2+4] Diels-Alder adducts with the C=N group of keto-imines. When compounds 328, derived from />-aminoacetophe-none and aromatic aldehydes, were reacted with a-diazo-/3-diketone 321, 2,3-dihydro-4//-l,3-oxazin-4-ones 329 were obtained via the addition of benzoylphenylketene to the C=N bond, and no formation of the corresponding C=0 adducts, 477-l,3-dioxin-4-ones, was observed (Equation 31) <2001J(P1)2266>. 

Such compounds are unstable unless the double bond is held in conjugation with other systems as, for example, when it is part of an aryl ring. Indeed, dihydro-3,1-benzoxazines are readily accessible from 2-aminobenzyl alcohols by condensation with aldehydes or ketones (Scheme 84) (75AP622). Oxacephems (199) also contain the 3,6-dihydro-2//-l,3-oxazine unit and they are formed for instance, on cyclization of chlorolactams (198) by the action of stannic chloride (B-80MI22701). 

Aminopropanols, when reacted with cyanogen bromide, also afford 2-amino-(or imino)-dihydro-1,3-oxazines (Scheme 90) (64ZOB3427), and related thiazines are formed when allylic isothiouronium salts (207) are cyclized with trifluoroacetic acid and stannic chloride. The necessary starting materials are synthesized from aldehydes or ketones by the action of vinylmagnesium chloride and subsequent treatment of the product allyl alcohols (206) first with hydrogen chloride and then with a thiourea (Scheme 91) (77JHC717). 

The ring opening of tetrahydro-l,3-oxazines to aldehydes has recently found wide application through the work of Meyers.2-3 2-Alkylidene-tetrahydro-l,3-oxazines, prepared from the readily available 5,6-dihydro-4//-1,3-oxazines, possess strong nucleophilic properties and can react with alkyl halides and carbonyl compounds. The derivatives so obtained can be reduced to tetrahydro-l,3-oxazines, and through ring opening the latter can furnish acyclic, alicyclic, and a,jS-unsaturated aldehydes and their C-l deuterated derivatives.221-223 228... 

Dihydro-(8//)-5,6-pyridazino[4,5-rf][l,3]oxazin-4-one (153) was prepared from the enamino aldehyde 4-methoxycarbonyl-5-formyl-2,3-dihydro(6//)-1,3-oxazine (152) with hydrazine hydrate in methanol (Equation (20)) <87CCC1773, 87CCC2953). Using the nitrile (154) the resulting pyr-idazinooxazine (155) carries an amino group at position 7 (Equation (21)). 

As imido esters, dihydro-1,3-oxazines of type 14 display reactivity similar to 2-oxazolines (see p 135). The a-C-H bonds of the 2-alkyl group are CH-acidic. They are metalated by reaction with butyllithium and then undergo C-C forming reactions with electrophiles such as haloalkanes, oxiranes or carbonyl compounds. The dihydro-1,3-oxazines 16, which are obtained from 15 by a-metalation and alkylation, undergo reduction with NaBH4 forming 17. Acid hydrolysis cleaves the cyclic aminal function of 17 yielding aldehydes 18 ... 

The anions derived from 2,4,4,6-tetramethyl-5,6-dihydro-l,3-oxazine have been used as the basis of several general synthetic procedures. Alkylation of the anion followed by reduction of the heterocyclic imine group and hydrolysis gives aldehydes. ... 

Benzyl-4,4,6-trimethyl-5,6-dihydro-4H-1,3-oxazine dissolved in tetrahydro-furan-ethanol (1 1), 9 N HGl added to pH 7, then aq. NaBH4 added at -30° with simultaneous addition of more HGl to keep the pH at 7, and stirred 1 hr. at -30° after the addition 2-benzyl-4,4,6-trimethyltetrahydro-l,3-oxazine. Y 88%. - Via this reduction, aldehydes, inch deuterioaldehydes, can be prepared from carboxylic acids and nitriles. F. e. s. A. I. Meyers and A. Nabeya, Ghem. Gommun. 1967, 1163. 

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