Phosphine-boranes alkylation

Quenching of the same lithiated species with CO2, followed by reduction of the carboxyUc acid functionality obtained with BH3-THF complex, yielded the next higher analogues 78 to these alcohols [94]. Subsequent treatment of the depro-tonated alcohols with TsCl or MsCl afforded (l )-l-boranato[alkyl(methyl)plios-phino] ethanol-2-tosylates or the mesylate phosphine-boranes in over 90% ee and excellent overall yields. 

Standard cyclisation methodology was used to access the cyclic monophosphinic acid derivative 78 by reaction of ammonium phosphonate and ethyldiisopropylamine, followed by the addition of chlorotrimethylsilane, with 2,2 -bis (bromomethyl)-l,l -biphenyl. Silane reduction of 78 gave the secondary phosphine. The secondary phosphine borane complex 79 could be used in alkylation or Michael addition reactions. For example the Michael adduct 80 was produced in high yield by treatment of 78 with a NaH suspension in THF followed by the addition of diethylvinylphosphonate . 

Lebel, H., Morin, S. and Paquet, V. (2003) Alkylation of phosphine boranes by phase-transfer catalysis. Org. Lett., 5, 2347. 

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. 

The selective preparation of various chlorophosphines used as building blocks for the preparation of polyfunctional phosphines is achieved using dichloro (diethylamino)phosphine (Et2NPCl2). Alkylation of this phosphine with organozinc halides furnishes, after borane treatment, protected aminodi-organophosphines. These in turn can be converted to the corresponding... 

Many phosphine-borane complexes Y3P BZ3 have been characterized. They include compouuds where Y = alkoxy, aUcyl, amino, halide, and hydride groups, and Z = alkyl, halide, and hydride. The stabilities of these complexes vary widely depending on the Lewis acidity and basicity of the boron and phosphorus moieties, respectively. The relative stabilities of Lewis acid-base complexes with BH3 are R3P > R3N > R3AS > R3Sb, but with BF3 the order is R3N > R3P > R3AS > RsSb. The stabihties of the borou halide complexes of phosphines follow the same order as the amine complexes BI3 > BBrs > BCI3 > BF3. 

Pt-catalyzed alkylations of bis(secondary) phosphines were diastereo- and enan-tioselective, yielding eiuiched mixtures of C2-symmetric rac and meso bis(tertiary) phosphines. Removal of the meso isomer by recrystallization of a phosphine— borane adduct enabled synthesis of the enantiomerically pure DiPAMP analog 39 by this approach (Scheme 64) [115]. 

Chiral phosphines are widely used as auxiliaries for various metal-catalyzed asymmetric reactions and can be prepared from stable phosphine-borane complexes. Secondary P-chiral phos-phine-boranes can be prepared by reductive lithiation of the corresponding tertiary phosphine-borane using LN (eq Likewise, P-chiral tertiary phosphine ligands can be produced by the reductive lithiation of phosphinite-boranes followed by alkylation, both proceeding with retention of configuration (eq 18). ... 

Since Evans et al. [78] has discovered that prochiral alkyl(dimefliyl) phosphine boranes can undergo the enantioselective deprotonation of one methyl group, using butyllithium and ( )-sparteine 141, these compounds have been widely used for the synthesis of P-chirogenic borane phosphines [79-105]. Lithium alkyls form chiral complexes 142 with sparteine 141 and related chiral diamines, which were investigated by single crystal X-ray analysis (Scheme 43) [82-87]. 

Such phosphine borane complexes have been tested in the catalytic asymmetric allyhc alkylation of l,3-diphenylpropene-2-yl acetate 120 with dimethyl malonate as nucleophile (Scheme 32). It was fbimd that the enantioselectivities strongly depend on the bite angle which is deeply affected by the nature of the spirocychc spacer and the direction of the coordinating phosphine groups. Representative X-ray stmctures of bisphosphine boranes 122 and 123 are shown in Scheme 32. Bisphosphine 119 afforded up to 74% ee while only 34% and 45% ee were obtained from the reactions using 122 and 123, respectively. 

Reaction of 31 with t-BuLi at very low temperature did not afford the expected tert-butylphosphine borane but prompted the metallation of 31 to form a solution of phosphide boranes 63. The steric bulk of the t-Bu carbanion probably accounts for this reactivity. Phosphide boranes are very nucleophilic, and can be protonated to form secondary phosphine boranes 64 or alkylated to produce tertiary phosphines, 65. The reported yields for these compounds are in the range of 21-75% with ee values up to 99%. Although no details of this reaction have been yet published, it is likely that this transformation will attract considerable attention because 64 are very versatile synthons for the preparation of many other P-stereogenic compounds. 

In short, the sequence enantioselective lithiation-electrophilic trapping-reductive elimination represents an enantioselective demethylation of 4 to produce optically pure 9. As seen through this book, secondary phosphine boranes are versatile synthons in P-stereogenic chemistry. In this case, they were alkylated with 2-(chloromethyl)benzothiophene providing phosphine boranes 10 in good yields, which were used in HPLC analysis to evaluate the optical purity of 9. 

Scheme 5.5 Preparation of enantioenriched secondary phosphine boranes and their alkylation.

Several diphosphine boranes have been prepared by taking advantage of the availability of a few optically pure secondary phosphine boranes (Section 5.2.1.1). After deprotonation, the phosphide boranes were easily alkylated by Az5(benzylic) substrates (Scheme 5.22). 

Another expansion of the BisP family was the preparation Ci-diphosphines with different alkyl groups on each phosphorus atom (unsymmetric BisP ligands), disclosed by Ohashi and Imamoto. " Unsymmetric BisP Kgands were prepared by coupling two of the precursors discussed in Section 5.2.1.1 the lithiated secondary phosphine boranes 9 and the mesylates or tosylates 33 (Scheme 5.32). 

While the formation of a variety of carbon stereocentres has been effectively achieved, stereoselective approaches for the preparation of P-stereogenic phosphines have, until recently, been non-existent. In this context, Bergman s group has developed several chiral ruthenium catalysts to be investigated for the enantioselective ruthenium-catalysed alkylation of secondary phosphines into the corresponding chiral air- and moisture-tolerant tertiary phosphine-borane products after a subsequent treatment with BHs.THF. " These reactions proceeded through the intermediacy of nucleophilic phosphido species, which had low barriers to pyramidal inversion, allowing a DKR process. 

Thanks to this general procedure, some classes of tetrathiahehcene-based alkyl and aryl phosphorous derivatives are now available, including phosphine—borane complexes (2015JO3921), phosphanes (2011EJO5649, 2013IC7995), phosphine oxides (2014EJO2694), and a diphosphonate (2011EJO5649). 

Advances in the use of anionic stereogenic phosphorus have been interesting. Acylation of lithium o-anisylphenylphosphide with chloro-formates bearing chiral alkyl groups provided a diastereomeric mixture that could be induced to undergo an inversion at phosphorus (at relatively low temperature) to form the more favorable diastereoisomer in a crystalline lattice.186 Subsequent conversion to the quaternary phos-phonium species was followed by removal of the acyl group and isolation of the chiral tertiary phosphine as the borane derivative (Equation 3.10). 

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