Secondary Phosphine-Boranes

Similarly to the P-CHj group, secondary phosphine-boranes react smoothly in the presence of a base (BuLi, NaH) under mild conditions to afford other kinds of functionalized phosphine-boranes in good to high yields, without racemi-zation. Yet the success of deprotonation/treatment with an electrophile process to afford substituted phosphine derivatives without any loss in optical purity may depend on the deprotonation agents employed. Use of butyllithium usually provides the products with high enantiomeric excess in good to high yields [73]. 

As mentioned in Sect. 3.1.1, secondary phosphine-boranes also react efficiently with aryl iodides in palladium-catalyzed substitution reactions (Pd(PPh3)4) [73]. In all cases the boranato functional group remains unchanged. 

P-Chirogenic diphosphine 19, which rhodium-chelate complex forms a seven-membered ring (rare case for P-stereogenic ligand), was also prepared in reasonable yield (68%) using the wide chemistry of secondary phosphine borane [37]. Deprotonation of the enantiomerically enriched ferf-butylmethylphos-phine-borane 88 (Scheme 15) followed by quenching with a,a -dichloro-o-xylene and recrystallization afforded optically active diphosphine-borane 89 (precursor of free phosphine 19). 

Scheme 17. Improved synthesis of optically active secondary phosphine-boranes...

Similar to the addition of secondary phosphine-borane complexes to alkynes described in Scheme 6.137, the same hydrophosphination agents can also be added to alkenes under broadly similar reaction conditions, leading to alkylarylphosphines (Scheme 6.138) [274], Again, the expected anti-Markovnikov addition products were obtained exclusively. In some cases, the additions also proceeded at room temperature, but required much longer reaction times (2 days). Treatment of the phosphine-borane complexes with a chiral alkene such as (-)-/ -pinene led to chiral cyclohexene derivatives through a radical-initiated ring-opening mechanism. In related work, Ackerman and coworkers described microwave-assisted Lewis acid-mediated inter-molecular hydroamination reactions of norbornene [275]. 

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 . 

The utilization of phosphine-boranes as stable forms of the phosphine has been exploited for addition reactions with alkenes. With several types of a,P-unsaturated compounds, Michael addition of primary phosphine-boranes has been accomplished in excellent yield for the preparation of secondary phosphine-boranes (Equation 3.30).443... 

Treatment of Cjq with lithiated secondary phosphine boranes or phosphinite boranes followed by removal of the BHj group afforded 1,2-hydrophosphorylated 27 in good yields (Scheme 3.14) [114, 117]. The phosphorus nucleophiles were generated by deprotonation of the corresponding borane complexes with Bull in THF-HMPA, and added to toluene solutions of Cjq at -78 °C. Complexes 26 are stable in air at room temperature for months. In the NMR spectrum, the proton of 26b appears... 

Pd-catalyzed cross-coupling of secondary phosphine-boranes and aryl iodides has been carried out in ionic liquids using a ligand immobilized with a pyridinium substituent (Fig. 3). Catalyst recycling at least six times without significant loss of activity was possible [93]. 

Scheme 56 Pd-catalyzed asymmetric phosphination with a secondary phosphine-borane...

The transformation of readily available enantiopure //-menthylphosphinates 2 into chiral phosphinous acid boranes 5 permits the elaboration of bulky P-stereogenic secondary phosphine boranes. Taking advantage of the synthetic potential of these compounds, abroad range of hindered P-chiral tertiary phosphine boranes 6 were prepared with excellent enantiomeric excesses [12,13]. Phosphinous acid 5 can easily be converted into one or the other enantiomer of the secondary phosphines boranes (Sp)- or (/ p)-6 by stereoselective reduction or substitution of the phosphinite borane derivatives, respectively (Scheme 4 and Table 1). 

The reaction of secondary phosphine boranes 211 with anisyl iodide, catalyzed by chiral Pd complex with (S,S)-Chiraphos, proceeded with retention of absolute configuration at phosphorus [135]. Addition of Pd((S,S)-Chiraphos)(o-An) to enantioenriched secondary phosphine 211 in the presence of NaOSiMc3 led to the formation of complex 212, stable at ambient temperature. This complex at +50°C in excess of diphenylacetylene allowed the formation of (/ p)-213 in yield of 70% and with enantiomeric purity of 98% ee (Scheme 68). 

Imamoto T, Tamura K, Ogura T, Ikematsu Y, Mayama D, Sugiya M (2010) Improved synthetic routes to methylene-bridged F-chirai diphosphine ligands via secondary phosphine-boranes. Tetrahedron Asymmetry 21 1522-1528... 

Pican S, Gaumont A-C (2005) Palladium catalysed enantioselective phosphination reactions using secondary phosphine-boranes and aryl iodide. J Chem Soc Chem Commun 2393-2395... 

Lemaire et al. developed a catalytic system for the reduction of secondary phosphine oxides to obtain secondary phosphine boranes using titanium(iv) isopropoxide as eatalyst and tetramethyldisiloxane as hydride source, giving excellent yields. ... 

The first method to be used for the preparation of (cT -cT ) cyclophosphino boranes was the thermal decomposition of secondary phosphine-borane adducts, formed by mixing diborane with a secondary phosphine. 

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). 

Many of the secondary phosphine boranes obtained with the menthol methodology have been deprotonated (usually with n-BuLi) and quenched with electrophiles leading to a variety of tertiary phosphine boranes (Table 2.13). 

Table 2.13 Phosphine boranes 54 prepared via deprotonation of secondary phosphine boranes 55 and electrophilic quenching (Scheme 2.20).

In this synthesis two cleavages of the phenyl-phosphorus bond by lithium afforded, after hydrolysis, the Aw(secondary) phosphine borane 109, which underwent cyclisation with dichloromethane upon deprotonation giving the... 

Secondary phosphine 195 was prepared from bromide 194 (derived from (P)-camphor) as an equimolar mixture of epimers. Upon liberation of the ketone group under acidic conditions, nucleophilic addition of the secondary phosphine borane took place, giving (/ p)-196 as the sole compound. Interestingly, in non-polar solvents the phospholane ring opened affording 197 as a mixture of epimers. 

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. 

The alkoxide group in 6 was acylated with trimethylacetyl (pivaloyl) chloride to furnish adducts 8 in very good yields. These products were found to be highly crystalline, allowing their optical purity to be increased to > 99% ee by a simple recrystallisation. Once optically pure, they were reduced by lithium naphthalenide and protonated with methanol affording the optically pure secondary phosphine boranes 9 (Table 5.2). 

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. 

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