Phosphinyl, reduction

Two technical applications of C = N-X substrates have been reported. Noyori s Ru-PP-NN catalyst system was successfully applied in a feasibility study by Dow Chirotech for the hydrogenation of a sulfonyl amidine [77], while Avecia showed the commercial viability of its CATHy catalyst based on a pentamethyl cyclopentadienyl Rh complex for the reduction of phosphinyl imines [78] (Fig. 34.11). 

Asymmetric reductions. The reagent can effect asymmetric reduction of alkyl aryl ketones and unhindered dialkyl ketones in high optical yield.1 It is the most useful reagent known to date for asymmetric reduction of even hindered a-keto esters to (S)-a-hydroxy esters in >90% ee.2 It is also effective for asymmetric reduction of phosphinyl imines of dialkyl ketones, RlR2C=NP(0)(C6H5)2 (50-84% ee).3... 

Transformation of a phosphonio-substituted phospholide derivative under conservation of the r-electron system has been demonstrated in a number of cases which include substitution of a ring-hydrogen atom, replacement of a PRs -moiety by a hydride, or reductive de-arylation of a PhsP " - to a phosphinyl substituent PPh2. Subsequent re-quaternisation of the latter allows the formal substitution of a PhsP " - by a modified Ph2(R)P -moiety in a two-step reaction. The application of this scheme is not only perfectly suitable for the synthesis of bis-phosphonio-benzophospholides with different phosphonio-moieties but, since the last reaction stage tolerates a variety of functional groups in the electrophile, offers as well a convenient pathway for the synthesis of side-chain functionalised phosphonio-phospholide derivatives from more simple substituted precursors. 

Reduction of 10 with lithium aluminum hydride (LAH) in ether furnished19 an intermediate, presumably the phosphine derivative 11, which was treated with acid to effect ring enlargement, giving the 5-phosphino-D-xylopyranose derivative 14. This compound was immediately converted by air oxidation19 into the stable crystalline compounds, 5-deoxy-3-0-methyl-5-C-(phosphinyl)-D-xylopyranose (15) and the 5-C-(hydroxyphosphinyl) derivative 16 in overall yields of 15 and 3.5%, respectively, from 10. Compound 16 was obtained in 90% yield from 15 by oxidation with bromine.19 No mutarotation was observed19 for compounds 15 and 16 in water during 48 h. 

The formation of a small proportion of the glucitol 138 is explained in terms of further reduction of the phosphinyl group of 131a to the 5-phosphino compound by an excess of SDMA, followed by intramolecular oxygen-transfer similar to that described in Scheme 2 for the formation of 96. 

Reduction of the mixture of 156a and 156b with SDMA gave a diaster-eoisomeric mixture of phosphinyl compounds 157, which was immediately hydrolyzed by acid, to afford 4,5-dideoxy-4-C-[(RS)-phenylphos-phinyl]-D-rifco- and -L-Zyro-furanose (158). The structure 158 was determined67 by 400-MHz, 1H-n.m.r. spectroscopy of the per-O-acetyl derivatives 159 these are l,2,3-tri-0-acetyl-4,5-dideoxy-4-C-[(RS)-... 

The synthesis uses Evans chemistry to introduce enantioselectively an azide group, which is then reduced to the a-amino group (Scheme 16). Note that in all cases, the phosphinyl group is protected as its sulfide during the synthesis to avoid complication (oxidation) observed with the phosphine. The phosphine sulfide is compatible with Fmoc- and Boc-peptide synthesis conditions. The free phosphine can later be regenerated by treating the sulfide with Raney nickel in MeOH (as shown in Scheme 15) or by methylation followed by treatment with HMPTJ50 This reduction was even applied successfully to sulfide-protected phosphine peptides still attached to the solid support.151 ... 

Specialty-chemical level production (kilograms) of phosphines is achieved by hydride reductions of halophosphines, phosphonyl halides and esters and phosphinyl halides and esters, e.g. ... 

The attachment of the strongly electronegative phosphinyl (P—O) group to an imine, usually via reaction of an oxime with a chlorophosphine, also gives highly electrophilic imines which are reduced by NaBFWTHF and various modified borohydride and LAH derivatives " under mild conditions. The product A-phosphinylamines are protected forms of primary amines since removal of the phosphorus substituent is accomplished under mild acidic conditions. Entries 12 and 13 (Table 16) present representative reductions and illustrate (entry 13) that highly diastereoselective reductions of cyclic systems to axial amine derivatives are accomplished with LiBHBu s. Enantioselective reductions of A-diphenylphosphinyl imines to optically active amine derivatives have also been reported (Chapter 1,7, this volume). ... 

Examples of other nucleophilic displacement reactions at tetracoordinate phosphorus, which proceed with retention of configuration and which involve systems possessing the necessary steric and electronic criteria for stereochemical analysis along the lines discussed above, include the alcoholysis and aminolysis of four-membered ring phosphinates and phosphinyl chlorides, respectively, and the HSiCh/triethylamine reduction of 17B Similar analysis of the base-catalyzed hydrolysis of 25 and 26 which, in contrast to the hydrolysis of acyclic analogsproceed with retention... 

Table 7. /l-Dialkyl(or Diamino)phosphinyl Alcohols by syn-Selective Reduction of the Corresponding Ketones with Sodium Borohydride... 

Ashfeld and coworkers proposed that the initial phosphinylation of oxime 2 and subsequent Staudinger-like reduction of the tosyl azide forms iminophosphorane 171 (Scheme 5.42k The formation of the phosphoryl bond upon rearrangement is a likely driving force behind the regioselective migration of the trans-oxime substituent (R in 171) to afford the nitriliumion 5. The corresponding anionic phosphoramide is released and then adds to the nitrilium ion amidine 17. A subsequent 1,3-phosphoryl shift leads to the final amidine product 173. 

A more selective means for incorporation of this ring system is to react the hydrogen phosphinate with benzoquinone by reductive addition to produce the phosphinyl-substituted hydroquinone (189,190). This can be used as a chain... 

Tang has reported a reductive phosphinylation approach for the synthesis of a-amino-phosphine oxides (Scheme 4.39) [90]. The nitrogen-containing precursor for this reaction was an amide, while the phosphorus precursor was a secondary phosphine oxide. Amides... 

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