Oxazaphospholidine oxides

Scheme 47 Synthesis of 2-phenyl-1,3,2 oxazaphospholidine-2-oxides 170a and 170b...

Treatment of 1,3,2-oxazaphospholidine 2-sulfide 176, bearing two amino residues at phosphorus, with oxaziridine 80 gave 1,3,2-oxazaphospholidine 2-oxide 177 in 92% yield <1997JOC6401>. It was interesting to note that the desulfurization occurred with complete stereoselectivity (>98% de) and with inversion of the configuration at the phosphoms, whereas use of w-chloroperbenzoic acid (MCPBA) resulted in retention of configuration affording 178 (Scheme 6). 

An X ray examination of the product from the interaction of (2B,4fi,5S)-(-)-3,4-dimethyl-2-phenyl-1,3,2-oxazaphospholidine 2-oxide with an aryl Grignard reagent has demonstrated that ring opening occurs with retention of configuration at phosphorus in accord with Inch s work, but at variance with that of Koizumi, and also in stereochemical opposition to that displayed by acyclic analogues (Mislow). Acid catalyzed alcoholysis of the acyclic phosphinic amide... 

Once again, the stereochemistry of reactions involving organolithium reagents has been investigated using substrates based on the 1,3,2-oxazaphospholidine skeleton. The reactions between the diastereoisomeric 2-methyl-1,3,2-oxazaphospholidine 2-oxides... 

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%) ... 

A similar synthesis of chiral (o-hydroxyaryl)oxazaphospholidine oxides 166a-b, 167a-b, and 169a-d derived from (5)-prolinol 127 and its diphenyl derivative 163 was achieved from precursors 164a-b, 165a-b, and 168 which were easily available from two different procedures as outlined in Scheme 46 [77], The first pathway gave the two expected diastereomers of 164 and 165 in a ratio... 

Scheme 46 Synthesis of (ohydroxyaryl)oxazaphospholidine oxides 166a-b and 167a-b and (ohydroxyaryl)oxazaphospholidine oxides 169a-d...

Alternatively, the ambident oi-hetero substituted allyl anions have been utilized as homoenolate equivalents. For example, in the presence of HMPA, allyl phenyl sulfides (251),192 allyl phenyl sulfones (252)192b c and allyl phenyl selenides (253)192d e add to a,(3-enones in a l,4(0)-mode, while allyl phenyl sulfoxides (254) and allyl phosphine oxides (255) afford 1 A j-addition exclusively, irrespective of solvent used.193 Hua has shown that additions of either chiral sulfoxide (254 R1 = R2 = R3 = R4 = H, R5 = p-tolyl) or allyl oxazaphospholidine oxide (256) occur with excellent enantioselectivity (>95% ee).194 Similarly, Ahlbrecht reports that the a-azaallyl (257) adds exclusively in a 1 A j-mode to acceptor (59) to afford 1,5-diketones (Scheme 86).195... 

The synthesis of various new chiral (o-hydroxyaryl)oxazaphospholidine oxides (139), derived from (S)-proline derivatives, from precursors (140) have been elaborated. This two-step reaction involves an unstable metallated intermediate that undergoes a fast 1,3-rearrangement with the formation of phosphorus-carbon bond. These catalysts have been successfully applied to the catalytic asymmetric borane reduction of numerous prochiral ketones with enantiomeric excess up to 84% ee (Scheme 35). ... 

In 1996, our group initiated a program of research dealing with the asymmetric borane reduction of ketones using oxazaphospholidine oxide compounds as catalysts [34]. 

A serial of related oxazaphospholidine oxides 27-31 were described, revealing that the presence of the second fused ring adjacent to the oxazaphospholidine was essential to obtain high catalytic activity. 

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. ... 

An oxazaborolidine 65 prepared from a-pinene is a new system. More drastic ariations are the oxazaphospholidine oxides, such as 66, which have been examined for their effectiveness in catalyzing the asymmetric reduction.The corresponding oxazaphospholidine-borane complex catalyzes the reduction of imines with diminished aereocontrol. 

The overall retention of configuration was rationalized by a reaction sequence involving attack of ferrocenyllithium (FcLi) on the electrophilic phosphorus followed by pseudo-rotation and termination by chloride elimination [64]. Ortho-lithiation of oxazaphospholidine oxide 113 was carried out with diastereoselectivity... 

Vinci D, Mateus N, Wu X, Hancock F, Steiner A, Xiao J (2006) Oxazaphospholidine-oxide as an efficient ortho-directing group for the diastereoselective deprotonation of ferrocene. 

Product 27 of entry 31 also deserves some comment since it was found that the oxazaphospholidine oxide group turns out to be an excellent ortho directing group for the diastereoselective lithiation of ferrocene (Scheme 3.15). 

In the last section several oxazaphospholidine oxides, obtained by oxidation of the P(III) precursor with t-BuOOH, have already been described. There is also one report by Juge and co-workers in which they prepare oxazaphospholidine oxides and sulfides by in situ deboronation/oxidation of oxazaphospholidine boranes. This section illustrates some more derivatives, prepared directly from P(V) species and ephedrine. Chronologically, these types of compounds were studied earlier than the corresponding P(III) counterparts. Nowadays oxazaphospholidine boranes, not oxides, are the most important precursors used to prepare enantiopure phosphorus ligands. However, apart from historic interest, ephedrine-derived oxazaphospholidine oxides, sulfides and selenides occupy an important place in the study of phosphorus stereochemistry and conformational analysis. Only a few examples are described here. 

The mentioned compounds have been used in systematic studies on the regio-and stereoselectivity of substitution reactions at the phosphorus atom. ° los.iii 112 The same authors also reported a similar study on oxazaphospholidine oxides and sulfides derived from (+)-norephedrine (Figure 3.3). 

There is one example reported by Koizumi and co-workers where phosphinates were prepared from bicylic oxazaphospholidine oxides or sulfides by the sequential nucleophilic substitution and acidic methanolysis (Scheme 4.52). 

Scheme 4.52 Preparation of a phosphinate from a bicyclic oxazaphospholidine oxide/ sulfide.

Methylmagnesium iodide reacted with 122 (X = O) with P-0 bond fission, to afford 123 in quantitative yield. Acidic methanolysis of this compound then produced (/ p)-124 in 92% ee. That implies that the first step occurred with inversion of configuration at the phosphorus atom, in contrast with oxazaphospholidine oxides derived from ephedrine. Similar inversion was observed for X = S and for other Grignard reagents. This example emphasises once more the difficulties of drawing general conclusions about the stereochemical outcome of the substitutions at the phosphorus atom. 

It has been shown that the nitrogen atom from the TPG displaces iodine, forming an oxazaphospholidine oxide ring (Scheme 16). ... 

A modification of this procedure allowed the isolation of 1,3,2-oxazaphospholidine 52a as a single diastereomer [41] and its application to asymmetric synthesis of enantiomerically and diastereomerically pure phosphinic acid derivatives 53 and 54 and tertiary phosphine oxides 55 (Scheme 20) [45], A few years later, a similar approach for the synthesis of enantiomerically pure tertiary phosphine oxides 55... 

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...

Oxazaphospholidines.—The phosphoranes (72) were obtained from phosphine-imines and epoxides as shown.49 Pyrolysis gave phosphine oxide and aziridines. The... 

Related catalysts for asymmetric borane reduction of ketones are open chain and cyclic phosphoric amides, in the oxidation state +3 or +5 (Scheme 11.3) [10, 11]. Early examples are the phosphonamides and phosphinamides 5a and 5b of Wills et al. [12] and the oxazaphospholidine-borane complex 6a of Buono et al. [13]. In the presence of 2-10 mol% catalysts 5a,b, co-chloroacetophenone was reduced by BH3 SMe2 with 35-46% ee [12]. For catalyst 6a a remarkable 92% ee was reported for the catalytic reduction of methyl iso-butyl ketone and 75% ee for acetophenone... 

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