Borane complexes of the H3PO2 P(III) tautomer: useful phosphinate equivalents

Abstract

The preparation and reactivity of novel (R 1 O)(R 2 O)P(BH 3 )H [R 1 , R 2 = Et, TIPS] synthons is investigated. The direct alkylation of these compounds with lithium hexamethyldisilazide (LiHMDS) and various electrophiles, provided new series of phosphonite-borane complexes, which can be converted into H-phosphinates and boranophosphonates.

Chemoselective Reduction of the P=O Bond in the Presence of P–O and P–N Bonds in Phosphonate and Phosphinate Derivatives

“…The reductions lead directly to the formation of the pertinent α‐hydroxy and α‐amino phosphonite‐boranes from their easily available and robust P=O precursors. This seems valuable, given that functionalized α‐hydroxy phosphonite‐boranes have currently only been obtained through multistep protocols . To the best of our knowledge, α‐amino phosphonite‐boranes as well as α‐amino phosphinite‐boranes have been neither studied nor synthesized before, despite their direct structural analogy to biologically highly relevant α‐amino phosphonic and α‐amino phosphinic acid derivatives…”

Temporary Protection of H‐Phosphinic Acids as a Synthetic Strategy

“…Even our protecting strategy based on phosphonite-borane complexes 7 obtained either from 5 or 9 (Scheme 1), [4] is not competitive since, for example, the simple hydrogenation of an alkene is sluggish (Eq 2), and if the same reaction is conducted in methanol, decomplexation of the borane takes place exclusively.…”

“…We recently reported one solution to this problem, based on borane complexes. [4] Since our methodologies provide compounds which cannot be made easily (or efficiently) from reagents 2 or 3 , we decided to investigate a protection strategy based on acetals. Perhaps surprisingly, few reports have described the reaction of H -phosphinates with orthoesters.…”

Synthesis of nucleoside 5′-boranophosphorothioate derivatives using an H-boranophosphonate monoester as a precursor

“…14 In fact, it has been reported that the reaction of (EtO) 2 P(→BH 3 )H with aldehydes at the phosphorus atom was readily promoted by deprotonation with i-Pr 2 NEt, whereas that of (i-Pr 3 SiO)(EtO)P(→BH 3 )H was not. 15 On the basis of this hypothesis, we employed the protection as a 9-fluorenylmethyl (Fm) ester because the protection could be easily carried out by condensation of the compound 1 with 9-fluorenylmethanol (FmOH) and it would also be easily deprotected by treatment with an amine under anhydrous conditions (Scheme 2). First, the compound 1 was allowed to condense with FmOH in the presence of bis(2-oxo-3-oxazolidinyl)phosphinic chloride (Bop-Cl) and Et 3 N. However, the product 4 once formed was slowly converted back into the starting material 1 in the reaction mixture.…”

“…Although the nucleoside 5-boranophosphorothioate monoester could not be isolated due to the instability of the compound, we consider that the new strategy using temporary protection of the H-boranophosphonate monoester moiety as a Fm diester will be useful to synthesize diverse P-doubly modified P-boronated 5nucleotide analogs. Many studies reported in the literature on the P-H functionalization of secondary phosphine-boranes by various reactions, such as alkylation and transition metalcatalyzed arylation, 18 as well as the recent study on the alkylation of H-boranophosphonate esters, such as (EtO) 2 P(→BH 3 )H and (i-Pr 3 SiO)(EtO)P(→BH 3 )H, 15 would be informative to explore this possibility. Evaluation of biological activity of the nucleoside 5boranophosphorothioate conjugates which were successfully synthesized in this study is also intriguing and will be presented elsewhere.…”