Phospholane 2-oxides

The stereochemistry of the addition has been recognized on the basis of structural features and chemical behavior of the complexes 9, produced in selected reactions of j with 1-ethoxy-1-oxo-2-phospholene 8. Neutralization of these complexes gave exclusively cis-3-substituted phospholane oxides J 0 while alkylation resulted in stereoselective formation of cis-3, cis- -disubstituted phospholane oxides JJ. The progress of the latter reaction was strongly dependent on the size of the alkyl groups involved. 

Intramolecular addition of a secondary phosphine oxide to a carbonyl group proceeds in the presence of an acid at room temperature to give both diastereomers of the product a-hydroxy-phospholane oxides 2 with the rfs-isomer predominating at higher temperatures the m-isomer is formed exclusively27. 

Handling, Storage, and Precautions readily oxidizes to the phospholane oxide upon exposure to atmospheric oxygen. The corresponding (allyl)Ni(BARF) complex is stable upon storage at room temperature for several days under a nitrogen atmosphere. 

Dimethylsulfonium methylide opening of the oxirane ring of erythro-phospholane epoxides (403) constitutes a simple approach to the synthesis of one carbon atom homologated allylic alcohols of phospholane oxide (404) (Figure 70). ... 

Historically, phospholanium salts have been prepared by quaternization in high yield of a selected phospholane with an alkyl halide. Although numerous methods exist for the preparation of the desired phospholanes (recently reviewed ), most of these have major drawbacks, including (1) very critical conditions, such as reaction time, dilution effects, and temperature (2) expensive and/or difficult to manipulate reagents and (3) the necessity of a multistep synthetic sequence giving overall low yields of phospholane. A general example of the latter would be the reaction of a substituted dihalophosphine with a 1,3-diene and hydrolysis to the phospholene oxide, which then can be catalytically reduced to the phospholane oxide and subsequently converted to the phospholane. ... 

The phospholene oxides resulting from the McCormack reaction also serve as highly useful starting materials for the synthesis of phospholane oxides by simple hydrogenation techniques (Equation (47)). 

Simpkins and coworker have reported desymmetrization of a meso-phos-pholane oxide involving discrimination of prochiral protons by a chiral lithium amide (Table 7) [78]. The addition of LiCl was effective to enhance the selectivity, probably due to lesser aggregation of the hthium salt [79]. In certain cases the enantiomeric excesses of the products could be increased up to 97% ee by recrystallization. The obtained phospholane oxides can be readily reduced to optically active phosphines, which are known to be useful as chiral ligands. 

Table 7. Enantioselective reaction of a mcso-phospholane oxide 1)...

Deprotonation-protonation is an alternative choice for asymmetric induction. Deprotonation of the meso-phospholane oxide with s-BuLi-(-)-sparteine and subsequent protonation with acetic acid afforded trans-phospholane oxide with 45 % ee together with the recovered raeso-phospholane oxide (Table 8) [80]. 

Table 8. Enantioselective protonation-deprotonation of a meso-phospholane oxide 1)s-BuLi/(-)-sparteine...

Trichlorsilane will reduce 1-phenyl phosphetanium oxide to 1-phenyl phosphetane, which with benzyl bromide gives the phosphetanium bromide. Hydrolysis of this phosphonium compound gives the original 1-phenyl phosphetanium oxide (6.827). However, hydrolysis of benzyl methyl phosphetanium bromide results in ring expansion to a phospholane oxide (6.828). 

Scheme 5.47 Des5mimetrisation of achiral phospholane oxide meso-llS.

Table 5.19 Stereoselective deprotonation of phospholane oxide meso- 5 (Scheme 5.47).

Some of the enantiopure phospholane oxides 116 were used for further transformations. For example, they could be isomerised by treatment with base for several hours in a protic solvent to afford 117 or subjected to a second deprotonation to produce 118 as a single isomer. Attempts to prepare Z)w(phospholanes) by double nucleophilic attack of the anions derived from 116 were unsuccessful. Some of the phospholane oxides were reduced with tri-chlorosilane/pyridine to afford the free phospholane with retention of configuration. The same strategy was applied to 1-phenylphospholane oxide but low yields of racemic products were obtained. This suggests that substrate 115 is probably a special case due to the formation of a more stable benzylic carbanion. ... 

The esterification of cyclic phosphinic acids such as l-hydroxy-3-phospholene oxides (7 and 8), 1-hydroxy-phospholane oxides (11 and 13), and l-hydroxy-l,2,3,4,5,6-hexahydrophosphinine oxide (15) was carried out in the presence of c. 15-fold excess of the alcohols in a closed vessel to afford the phosphinates (9,10,12,14, and 16) in acceptable to excellent (44-95%) yields [33-37]. The method elaborated seems to be of general value. It was foxmd that the esterification of phosphinic acids is thermoneutral and kinetically controlled, and also represented as an irreversible process [35]. 

After the esterifications and thioesterifications, the direct amidation of cyclic phosphinic acids was also attempted. The interaction of l-hydroxy-3-phospholene oxide (7) and 1-hydroxy-phospholane oxides (11 and 13) with primary amines under MW conditions took place in conversions of ca. 33% (Scheme 5). The amides (18-20) were isolated with 23-29% yields [37,39]. 

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