2- -oxazine with sodium borohydride

H)-oxazine with sodium borohydride, 51, 25 a-Phenylcyclopropane, 52, 32 1-Phenylcyclopropanecarboxal-dehyde, from 2-benzyl-4,4,... 

Meyers et al.221-222 showed that tetrahydro-l,3-oxazines exist in tautomeric ring-chain forms [Eq. (62)]. When a 5,6-dihydro-l,3-oxazine is reduced to a tetrahydro-l,3-oxazine, some 3-aminoalcohol can also be formed through the reduction of the open-chain imino form [cf. Eq. (62)]. To avoid this the reduction should be carried out with sodium borohydride at - 40°C. 

The scope of the synthesis was extended by using a 2-vinyloxazine, which led to the formation of propionaldehyde derivatives.227 Another modification of the aldehyde synthesis started with quaternary salts that were treated with sodium hydride, alkylated, then reduced with sodium borohydride to tetrahydro-l,3-oxazines.229... 

Much interest lies in the use of dihydro-1,3-oxazines (190) as enolate equivalents, since, if an alkyl group is carried at C-2, these compounds may be deprotonated and the anions formed reacted with numerous types of electrophiles. Reduction of the imine bond of the products (191), is then conveniently effected by treatment with sodium borohydride. The tetrahydrooxazines (192) which are formed may then be ring opened by hydrolysis with aqueous acid (Scheme 15). This topic and its utility in synthesis has been well reviewed. - ... 

As for dihydro-1,3-oxazines, perhydro-1,3-oxazine methiodides (125) are ring-opened by reaction with sodium borohydride. The products obtained depend upon the conditions used thus, in anhydrous tetrahydrofuran tertiary amines and their borane derivatives are formed, but in ethanol or methanol transesterification occurs to give the corresponding ethyl or methyl ethers (Scheme 32) <90H(31)2079>. 

The amidomercuriation of )- or (Z)-allyl acylaminomethyl ethers (360) with mercury trifluoro-acetate, followed by reduction with sodium borohydride, leads to mixtures of oxazolidines (361) and 1,3-oxazines (362), the composition of the mixtures depending upon the reaction times (Scheme 98) <88TL3789>. 

Michael addition to (+)-pu]egone [( + )-12] is not only possible with carbon nucleophiles, but also nitrogen and sulfur compounds. Thus, reaction of (+)-pulegone with benzylamine, followed by reduction of the carbonyl group with sodium borohydride, gives (1 / .3/ ,4,S )-8-(ben-zylamino)menthol (24)28, used for the formation of chiral 1.3-oxazines which react with Grignard reagents diastereoselectively (Section D. 1.3.1.4.). 

Sodium, with l-bromo-3-chloro-cyclobutane to give bicyclo [l.l.O]butane, 51, 55 Sodium amalgam, 50, 50, 51 Sodium amide, with 2,4-pentane-dione and diphenyliodonium chloride to give l-phenyl-2, 4-pentanedione, 51, 128 Sodium azide, 50, 107 with mixed carboxylic-carbonic anhydrides, 51, 49 Sodium borohydride, reduction of erythro-3-methanesulfony-loxy-2-butyl cyclobutanecar-boxylate, 51, 12 reduction of 2-(1-phenylcyclo-pentyl)-4,4,6-trimethyl-5,6-dihydro-1,3(4H)-oxazine to 2-(1-phenylcyclopentyl)-4,4, 6-trimethyltetrahydro-l,3-oxazine, 51, 25 Sodium cyanoborohydride, used... 

B. 2- (1-Phenylcyclopentyl)-4,4,6-trimethyltetrahydro-1, Z-oxa-zim. To a 600-ml. beaker containing a magnetic stirring bar are added 200 ml. of tetrahydrofuran, 200 ml. of 95% ethyl alcohol, and 25.0 g. (0.092 mole) of the oxazine obtained in Part A. The mixture is stirred and cooled to —35 to —40° with an acetone bath to which dry ice is added as needed. A 9N hydrochloric acid solution is added dropwise to the stirred solution until an approximate pH of 7 is obtained as determined by pll paper. A solution of sodium borohydride is prepared by dissolving 5.0 g. (0.13 mole) in a minimum amount of water... 

Sodium borohydride is an effective reductant for the imine bond of dihydro-1,3-oxazines affording tetrahydro derivatives, but predictably where lactam or sultam functions form part of the heterocycle, treatment with lithium aluminum hydride is necessary. Dihydro-1,3-benzothiazinones for instance are reduced by this reagent to the corresponding dihydroben-zothiazines (Scheme 29) <77ACH(92)317). 

The first step consists of the formation of lithio salts by treatment of 5,6-dihydrooxazines with phenyl-, n-butyl-, or t-butyllithium in tetra-hydrofuran at -780.1,3,22,223 The lithio salts can readily be alkylated by alkyl halides to 75, and the product can be reduced with aqueous sodium borohydride (or borodeuteride) at pH 7 in tetrahydrofuran-ethanol-water at -35° to -45°C to tetrahydro-l,3-oxazines (76) in quantitative yield. The latter 224-228 23e on hydrolysis with aqueous oxalic acid give aldehydes (77) [Eq. (63)]. 

Aldehydes can be alkylated indirectly via the corresponding imines lithium dialkylamides readily deprotonate such imines at the position a to the azomethine group, and the carbanions formed can be alkylated with primary halides. This route to a-substituted aldehydes avoids the use of sodium borohydride, necessary in the dihydro-1,3-oxazine alternative. 

Olefinic aldehydes have been synthesized by a variety of methods including oxidation of the corresponding primary alcohols with the chromium trioxide-pyridine complex 195—197) or N-chlorosuccinimide-dimethyl sulfide complex 198), heating a primary alken-l-yl mesylate with dimethylsulfoxide 199), or by alkylation of the lithium salt of 5,6-dihydro-2,4,4,6-tetramethyl-l,3-(4H)-oxazine with an alkynyl iodide followed by sodium borohydride reduction and acid hydrolysis (200). 

---