Phosphine boranes resolution

P-Chiral phosphine-borane compounds were synthesized through lipase-catalyzed optical resolution (Figure 17 (d)).18e Alkyl(l-hydroxymethyl)phosphine-boranes (up to ee 99% ) were obtained using lipase AK or CAL. 

Although no mechanism was proposed, the Pd(Me-DuPhos)-catalyzed asymmetric hydrophosphination of an alkyne with a phosphine-borane under kinetic resolution conditions (Scheme 6) presumably involves similar insertion and reductive elimination steps [14]. 

Pd-catalyzed asymmetric arylation of a phosphine-borane, under kinetic resolution conditions, gave enantioenriched phosphine-borane 36. Slowing reductive elimination with a Pd-CsFs group enabled isolation and separation of the diaster-eomers of an analog of the key intermediate (Scheme 56) [94]. The stereochemical details of Pd-P bond formation and P-C reductive elimination, which both proceed with retention at phosphorus, had been elucidated earlier in related Pd(Chiraphos) complexes [95, 96]. 

For example, Mikolajczyk and Kielbasinski [172-175] studied the acylation of phosphine boranes 259 using CAL (Chirazyme ) lipase from Candida Antarctica and Lipase AK from Pseudomonas fluorescencs (Scheme 84). The best enantios-electivity was attained in the lipase AK-catalyzed acylation of 259 in cyclohexane solution with vinyl butyrate as an acyl donor (99% ee) for unreacted hydroxypho-sphinate 259 and 43% ee for the acylated product 260. The E-values were on the level of 15. The enzymatic resolution of alkoxy (hydroxymethyl)phenyl-phosphine boranes (/ /S)-261 was achieved by trans-esterification with vinyl acetate in the presence of CALB, Amano AK, Amano PS, Amano AH, and LPL in various solvents. The best enantioselectivity of imreacted alcohol 261 and acylated product 262 was attained in cyclohexane (37% ee, conversion 50%). Kielbasinski [176] recently reported some additional data, including theoretical calculations and more accurate chemical correlation, which proved that the borane reduction of acyclic phosphine oxides proceeded with inversion of configuration at the phosphoms center. On this basis, the stereochemistry of the enzymatic reaction was ultimately determined (Scheme 85). 

Scheme 85 Enzymatic resolution of alkoxy (hydroxymethyl)phenyl-phosphine boranes 261...

The first kinetic resolutions of phosphine boranes have been recently reported by O Brien and co-workers (entry 5), via deprotonation with, s-BuLi/(-)-sp. With this procedure, products with up to 82% ee were obtained. 

In the early studies, the phosphine oxides resolved contained substituents with aromatic condensed rings (entries 2 and 3) but later other oxides without that substitution were also resolved (entries 1 and 5) and even secondary phosphine oxides (entry 7). Entries 8-15 show some resolutions of the phosphine boranes including examples with several stereogenic centres in the backbone (entries 11-14). Compound of entry 11 can be regarded as a hybrid between BPE and DiPAMP. A few diastereomeric pairs have also been resolved by HPLC (entries 16 and 17), because conventional methods such as column chromatography or recrystallisation failed. 

A limitation of the method is that all the phosphine boranes of Table 2.6 bear the -P(BH3)(f-Bu)Ph group. The dynamie resolution procedure could become much more versatile method if it could be applied to wide variety of secondary phosphine boranes. Surprisingly, this subject has been scarcely studied and only a few other aryldialkylphosphine boranes have been prepared (Scheme 2.7 and Table 2.7). 

Examples of electrophilic addition of secondary phosphines to alkenes or alkynes were described. [114, 124, 125, 135]. Glueck [124-126] reported enantioselective tandem reaction of alkylated/arylation of primary phosphines catalyzed by platinum complex, proceeding with formation of chiral phosphaace-naphthenes. Palladium-catalyzed hydrophosphination of alkynes 219 tmder kinetic resolution conditions gave access to 1,1-disubstituted vinylphosphine boranes 220. However, despite screening several chiral ligands, temperatures, and solvents, the... 

The lipase-promoted kinetic resolution of a series of P-boranes (854) which might be treated as phosphinic acid derivatives, proceeded with moderate stereoselectivity to give both the unreacted substrates (855) and their O-acetyl derivatives (856) (Scheme 214). Some additional studies were carried out which proved that the borane reduction proceeded with inversion of configuration at the phosphorus center. ... 

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