L,3,2-Oxazaphospholidine-2-oxide

The first report on the reaction of D-pseudoephedrine 66 with phosphoryl chloride appeared as early as 1962 [49], More recently it was found that this condensation gave 2-chloro-l,3,2-oxazaphospholidine 2-oxides 67 as a single diastereomer which was subsequently esterified with racemic aldehyde cyanohydrins 68 without racemization at the phosphorus atom. The prepared diastereomeric esters 69 were used as substrates for the asymmetric synthesis of optically active cyanohydrins 72, which involves the intermediate formation of the tertiary esters 70, as shown in Scheme 22 [50],... 

A similar reaction of (-)-ephedrine (42) was reported to give 2-chloro-l,3, 2-oxazaphospholidine 2-oxide either as a single diastereomer (25,45,5R)-73a [51-53] or as the isomeric pair 73a,b, which could be separated by chromatography over silica gel (Scheme 23) [32, 54],... 

Chloro-l,3,2 oxazaphospholidine-2-oxide 158a was formed stereoselectively in the reaction of (l/ ,2/ )-(-)-a-(l-isopropylaminoethyl)benzyl alcohol 157 and phosphoryl chloride in the presence of triethylamine (Scheme 44) [65, 75],... 

M-Benzyl-O-methyl-L-serinoate (173) was condensed with phosphoryl trichloride giving cyclic chloridate 174 that reacted with the Tegafur derivative 175 with the formation of almost equal amounts of 2-alkoxy-l,3,2 oxazaphospholidine-2-oxides 176a and 176b (Scheme 49) [80],... 

Scheme 49 Synthesis of 2-alkoxy-l,3,2 oxazaphospholidine-2-oxides 176a and 176b...

A rich family of 2-alkoxycarbonyl-l,3,2-oxazaphospholidine-2-oxides 179-181 was prepared from the reaction of camphor derived aminoalcohols 177 and 178 with either methoxycarbonyl phosphonic dichloride or ethyl dichlorophosphite followed by the reaction with methyl bromoacetate. The reaction with aminoalcohol 177a afforded the phosphorus epimers 179 and 180, in ratios from 1/1 to 12/1 depending on the iV-substituent which could be separated easily by column chromatography. The reaction with aminoalcohols 178a-c, however, gave a single epimer 181a-c in each case (Scheme 50) [81]. 

A similar condensation of 177b with chloromethyl phosphonic dichloride gave 2-chloromethyl-l,3,2-oxazaphospholidine-2-oxide 182 which was converted into the cyano derivative 183 by reaction with potassium cyanide in anhydrous dimethyl-sulfoxide (Scheme 51) [82],... 

Scheme 51 Synthesis of 2-chloromethyl-l,3.2-oxazaphospholidine-2-oxide 182 and its conver-tion into the cyano derivative 183...

The use of a chiral template of an entirely different nature also provided useful stereochemical data the phosphoroamidic chloride 166 and prop-2-enylmagnesium bromide provide a product which consists entirely of (25)p-3-isopropyl-4-methyl-5-phenyl-2-(prop-2-enyl)-l,3,2-oxazaphospholidine 2-oxide (167). ... 

Chirality in the phosphorus-containing dienophile induces a preferential mode of approach to the diene the (2R,45)-l,3,2-oxazaphospholidine 2-oxide 480 reacts with cyclopentadiene to give a 10 19 ratio (96% total yield) of the endo (structure confirmed by X-ray crystallography) and exo adducts, and a similar reaction with the IS, 45)-1,3,2-oxazaphospholidine 2-oxide gave endo and exo products in the ratio 2 3, with considerable diastereoisomeric excesses (80-88%) ... 

Phosphorus-containing Ring Systems. - A range of new chiral oxazaphospholidine oxides 266 and 267 have been synthesised and used as catalysts in asymmetric reductions of ketones with diborane. Mannich-type cyclisation reactions of 5-amino-3-benzylthio-4-cyano(ethoxycarbonyl)pyrazoles with dichlorophenylphosphine and aromatic aldehydes in the presence of cation exchange resin have been used to prepare a number of 6-oxo-6-phospha-4,5,6-trihydroimidazolo[l,2-b]pyrazoles, e.g. 268. Some of these compounds have herbicidal activity and this report is typical of a number of similar ones in the Chinese literature. A number of metallocycles, e.g. 269, have been reported as products from reactions of transient zirconocene-benzyne intermediates with phosphaimines followed by sulfuration or selenation. ... 

The same ylide reacts analogously, but less effectively when exposed to benzonitrile oxide 4,4-ethylene-3,5,5,5-tetraphenyl-l,2,5-oxazaphospholidine was obtained in 61% yield.This heterocycle is unstable when treated with iodomethane. 

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