Oxazaphospholidine boranes

Applications of oxazaphospholidine-borane complexes, cyclic phosphoramides, compounds with N—P=0 function, and other P-heterocycles in enantio-selective catalysis 99SL377. 

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... 

Nevertheless, this mechanism cannot fully explain the enantioselectivity encountered. In the same area, Martens et al. have reported the synthesis of numerous oxazaphospholidine borane complexes and their use in the enantiose-... 

In 1996, the enantioselective borane reduction of imines catalyzed by an oxazaphospholidine-borane complex in refluxing toluene has been described. Thus, optically active amines have been obtained with enantioselectivities up to 63% [33]. 

As described in the catalytic enantioselective borane reduction of ketones using oxazaphospholidine-borane complexes, a mechanistic rationale has been proposed. Nevertheless, this mechanism cannot fully explain the enantioselec-tivity encountered. 

Routes to the chiral ferrocenyldiphosphines 113 have been developed, via the use of the chiral oxazaphospholidine borane 114. Routes to other chiral ferrocenylphosphines have also been developed, including the boranato-functio-nalised systems 115, and the C2-symmetric diphosphine 116, having only the planar chirality of the ferrocene system. Full details have now appeared of the palladium-promoted asymmetric Diels-Alder reaction between l-phenyI-3,4-di-... 

Keywords Hydroboration, Ketone, Reduction, Oxazaborolidine, Oxazaphospholidine, Borane, Borohydride... 

Oxazaphospholidine-Borane Complex as a Borane Reduction Catalyst... 

Recently Buono has reported a new class of efficient catalyst systems which contains a chiral oxazaphospholidine-borane complex as a catalyst in the borane reduction of ketones[115, 116]. The oxazaphospholidine-borane complex 75 is easily prepared by action of 1.3 equiv. of BH3 THF on (2R, 5S)-2-phenyl-3-oxa-... 

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. 

Juge developed a powerful method (Juge-Stephan method) [1, 51] for the preparation of / -stereogenic phosphines based on the use of ephedrine as a chiral auxiliary. The key reactants in this methodology are 1,3,2-oxazaphospholidine boranes 78, prepared by a one-pot reaction from bis(diethylamino)phenylphosphine and (—)-ephedrine, followed by protection with BH3. The cyclization of the (—)-ephedrine takes place stereoselectively, with preferential formation of the (/ p)-diastereoisomer in 90% de [52, 53]. The absolute configuration at the phosphorus atom has been determined by chemical correlations and NMR analysis, and proved by X-ray analysis [54]. Oxazaphospholidines react readily with electrophiles or nucleophiles to provide various chiral phosphorus compounds. Enantiomeric antipodes of tertiary phosphines (Sp)-79 and (Rp)-81 were obtained from (-1-)- or (-)-ephedrine, as shown in Scheme 25. The configuration at the E-atom is controlled by the configuration at the Ph-substituted Cj of (-i-)-pseudoephedrine or ( )-ephedrine, respectively. This was confirmed by X-ray crystal-structure analyses of two intermediate compounds in the synthetic route to the chiral triarylborane-phosphine adducts [54]. 

Oxazaphospholidine boranes 82 react regio- and stereoselectively with alkyl lithiums or aryl lithiums in THE at —78°C, with formation of acyclic phosphinite boranes 83. Various substituents R =n-alkyl, c-alkyl, aryl, or ferrocenyl were introduced into aminophosphine boranes 82 in high yield (93-97%) and with high diastereoselectivity dr >98 2). The reaction proceeded with retention of configuration at phosphorus. RecrystaUization of aminophosphine boranes 83 in propanol gave the diastereoisomerically pure products [53]. Acid methanolysis of aminophosphine boranes 83 led to the formation of phosphinite boranes 84 with inversion of configuration on the E-center to yield the compotmds 84 in high... 

Scheme 26 Syntheses of PAMREHa 86 and DIPAMP 87 tiom oxazaphospholidine borane 82...

The synthesis of P-chiral diarylphosphinocarboxylic acids 120 was achieved with excellent enantiopurity starting from the oxazaphospholidine boranes 82. Amido- and amino-diphosphine ligands 121, containing an L-proline backbone, were also derived from 82. The catalytic activities of the ligands 121 were evaluated in the Pd-catalyzed allylic alkylation reaction of 1,3-diphenylpropenyl acetate (Scheme 36) [66]. 

Scheme 3.17 Stepwise cyclisation of ( )-ephedrine to prepare oxazaphospholidine boranes (24).

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. 

Alcohol 61 is easily prepared from a chemical found in industrial waste and was used to prepare the tricyclic oxazaphospholidine borane 62 in 64% combined yield. The X-ray structure revealed that in this case the phosphorus atom had S absolute configuration. In the same paper they described the preparation of 64 in 40% yield and in optically pure form, starting from the azetidinic alcohol 63. The same authors prepared the phosphine oxide version of 62 via oxidation of the P(III) precursor and by direct reaction of 61 with PhP(0)Cl2/NEt3. 

Martens and co-workers used several oxazaphospholidine boranes to prepare methylphosphinite boranes (Scheme 4.54). 

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