Phosphines and Phosphine Boranes

Phosphine boranes, adducts between phosphines and a BH3 unit, have been known for over 70 years but it was not until the 1990s that they became essential intermediates in the synthesis of P-stereogenic compounds, thanks to 

Imamoto and co-workers developed procedure B, which is a one-pot transformation of phosphine oxides into phosphine boranes. The cerium cation plays two roles it coordinates to the phosphoryl group to make the deoxygenation with LiAlH4 possible and it also facilitates the reaction between 

NaBH4 and the intermediate free phosphine. Unfortunately, starting from optically pure phosphine oxides yielded only racemic phosphine boranes. Finally, Corey and co-workers ° prepared optically pure phosphine boranes by in situ desulfurisation-complexation (method C), with retention of configuration. 

Phosphine boranes would not be so popular if the borane group could not be easily removed. Two reliable methods have been developed. The first one is the treatment of phosphine boranes with amines (D) or alcohols, which act as borane acceptors. Although phosphine boranes are in general more stable than amine boranes, the presence of a large excess of a basic amine frequently suffices to displace the equilibrium and deprotect completely the phosphine. Typical amines used for this transformation are diethylamine, TMEDA, pyrrolidines, morpholine and DABCO. The reactions are usually carried out at room temperature or with moderate heating in neat amine with the exception of DABCO, which as it is a solid is typically used in toluene. 

Trialkylphosphine boranes are electron rich and possess very inert P-B bonds. These compounds are incompletely deprotected by amines but are efficiently deboronated by method E, developed by McKinstry, Livinghouse and co-workers. Treatment of phosphine boranes with an excess of certain strong acids such as methanesulfonic, trifluoromethanesulfonic or more often tetrafluoroboric in dichloromethane at low temperature (— 5 °C to room temperature) cleaves the borane group producing phosphonium salts, which are extracted with an aqueous base (NaOH or NaHCOs) to afford tertiary phosphines in good yields. The mechanism of the decomplexation is not clear, but it is thought to involve nucleophilic substitutions at the borane moiety, eventually leading to decoordination. 

---

Rajendran KV, Gilheany DG (2012) Identificatiem of a key intermeeliate in the asymmetric Appel process one pot stereoselective synthesis of F-stereogemic phosphines and phosphine boranes fiom racemic phosphine oxides. J Chem Soc Chem Commun 48 10040-10042... 

Borohydride salts react with trivalent phosphorus compounds to give a variety of boranes, phosphines and phosphine-borane adducts (9.20-9.23). The reaction between sodium borohydride and phosphorofluoridic acid produces diborane in about 80% yield, and is a convenient method of preparation of the latter. 

Optically pure, trivalent P-stereogenic compounds are prepared by several methods, diseussed in Chapters 2-6. Most of the syntheses are multi-step processes that involve tetra- or pentaeoordinated intermediates. Two families of compounds, phosphine oxides and phosphine boranes are by far the most important direet preeursors of free phosphines. The interconversions between phosphines and phosphine boranes and oxides are briefly discussed in this section. 

It is now well-established that unsymmetrical substituted menthylphosphinates, RR P(0)0Men, as well as the corresponding phosphine-boranes RR P(BH3)OMen and phosphinothioates RR P(S)OMen, can be separated readily into the di-astereomeric forms, and subsequently reacted with Grignard reagents to afford P-chirogenic tertiary phosphines with a high degree of stereospecificity [57]. The... 

Phosphine-borane 63a (75% ee) was obtained by reduction of compound (Sp)-62a using LDBB at -60°C and nucleophilic substitution with iodomethane in 72 % yield. The observed loss of optical purity may be ascribed to stereomutation of the generated tricoordinated phosphorus species. Recrystallization afforded (S)-63a in > 99% ee. On the other hand, severe racemization was observed using the same method with (Rp)-62b. An alternative strategy consisted of deborana-tion of (Rp)-62b using ZSl-methylpyrrolidine, methylation with methyl triflate. 

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. 

P-Chirogenic phosphine/sulfide hybrid phosphine-boranes 80 were synthesized from the reaction between (l )-tosylates 79 [94] and sodium thiolate in DMF at ambient temperature as depicted in Scheme 12, or alternatively by a one pot synthesis consisting of the nucleophilic attack of the chirally induced hthium salt of 74 on phenyl disulfide. Both methodologies provided the desired sul-fide/phosphine boranes in excellent yields [10]. 

The same phosphine-borane used for the synthesis of BisP acted as the starting materials of the construction of MiniPHOS, the next smaller analogue to BisP (Scheme 13). The chirally induced lithium salt was treated with alkylphos-phorus dichloride, methylmagnesium bromide, and borane-THF complex to afford enantiomerically pure MiniPHOS-borane 82a. Recrystallization enabled elimination of a small amount of corresponding raeso-diastereomer formed [29]. Yields were generally low, ranging from 13 to 28%. 

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). 

Nickel and palladium complexes also catalyze the formation of the carbon-phosphorus bonds in phosphorus(V) and phosphorus(III) compounds. Indeed, this chemistry has become a common way to prepare phosphine ligands by the catalytic formation of phosphine oxides and subsequent reduction, by the formation of phosphine boranes and subsequent decomplexation, or by the formation of phosphines directly. The catalytic formation of both aryl and vinyl carbon phosphorus bonds has been accomplished. 

Although more hydrolytically sensitive than the phosphine boranes, diorganochlorophosphines can be more accessible than diorganophosphines and are not pyrophoric. Thus, the reaction of a chlorophosphine with an aryl halide or aryl triflate in the presence of zinc as a reducing agent and (DPPE)NiCl2 as catalyst provides a convenient procedure for P—C coupling (Equation (49)).150 A related nickel-catalyzed process driven by electrochemical reduction has also been reported 151... 

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 . 

Bourumeau, K., Gaumont, A.-C., and Denis, J.-M., Hydrophosphinylation of a,P-unsaturated esters by primary phosphine-boranes a useful entry to symmetrical and unsymmetrical phosphine-boranes, Tetrahedron Lett., 38, 1923, 1997. 

The reaction (a Schlenk dimerization) between the phosphine-borane-substituted alkene nPr2P(BH3) (Me3Si)C=CH2 and elemental lithium in THF yields the complex [(pmdeta)Li Prn2P(BH3) (Me3Si)CCH2]2 123 which in the solid state has a lithium bound to the BH3 hydrogens of the ligand, and no Li-C(carbanion) contact (pmdeta = N,N,N, N",N"-pentamethyldiethylenetriamine).85... 

Tris(trimethylsilyl)silane reacts with phosphine sulfides and phosphine selen-ides under free radical conditions to give the corresponding phosphines or, after treatment with BH3-THF, the corresponding phosphine-borane complex in good to excellent yields (Reaction 4.45) [82]. Stereochemical studies on P-chiral phosphine sulphides showed that these reductions proceed with retention of configuration. An example is given in Reaction (4.46). 

The proton n.m.r. spectra of these adducts have been intensively studied. The BH3 resonance in the spectrum of CHjPHj BH3 consists of a 1 1 1 1 quartet due of coupling between the boron nucleus ( B, 80% natural abundance /= 3/2) and the directly bonded protons (/bh" = 99 Hz). Each component of the quartet is further split into a doublet of triplets due to coupling with the phosphorus nucleus (/pH" = 16 Hz) and the two protons bonded to phosphorus, respectively. The PH -signal is, as is typical for phosphine-borane adducts, a doublet with/pH = 375 Hz. All n.m.r. data for the two types of adducts are given in Table 11. 

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... 

---