Lithium‐Aluminate‐Catalyzed Hydrophosphination Applications

Abstract Synthesized, isolated, and characterized by X‐ray crystallography and NMR spectroscopic studies, lithium phosphidoaluminate iBu3AlPPh2Li(THF)3 has been tested as a catalyst for hydrophosphination of alkynes, alkenes, and carbodiimides. Based on the collective evidence of stoichiometric reactions, NMR monitoring studies, kinetic analysis, and DFT calculations, a mechanism involving deprotonation, alkyne insertion, and protonolysis is proposed for the [iBu3AlHLi]2 aluminate catalyzed hydrophosphination of alkynes with diphenylphosphine. This study enhances further the development of transition‐metal‐free, atom‐economical homogeneous catalysis using common sustainable main‐group metals.

Bimetallic ate complexes,w hich can synergistically enhance stoichiometric reactivities over their neutral monometallic components,a re ac ore theme of our research. [13] Recently expanding this work into the catalytic regime,w e used lithium aluminates as catalysts for hydroboration of aldehydes,k etones,i mines and acetylenes. [14] In general, the charged bimetallic species proved more active catalysts than their neutral monometallic components. [14b] Herein, we probe the ability of our most active lithium aluminate,[iBu 3 AlHLi] 2 , 1,a sacatalyst for hydrophosphination of alkynes,a lkenes, and carbodiimides.
Aware that dehydrocoupling can compete with hydrophosphination, ac ontrol reaction between HPPh 2 and 10 mol %o f2 in [D 8 ]toluene was heated at 110 8 8Cf or 20 h. Less than 15 %ofHPPh 2 had undergone dehydrocoupling to form 1,1,2,2-tetraphenyl diphosphine (determined by 31 PNMR spectra), signifying that this is unlikely to be as ignificant problem in this system. Subsequently 2 was tested as ac atalyst for the hydrophosphination of alkynes under the previously optimized conditions (10 mol %[ Al], [D 8 ]toluene,1 10 8 8C; Table 1). Forp henylacetylene,a95 % conversion (1:3 E/Z ratio) of the anti-Markovnikov product was obtained after 20 h( compare 72 %u sing 1), albeit with reduced E/Z stereoselectivity.B yc ontrast, Watermanst in catalyst Cp* 2 SnCl 2 is poorly active for PhCCH (10 mol % catalyst, 18 h, 65 8 8C, 4% yield). [7b] Using 2,h ydrophosphination is much faster with internal alkynes than terminal alkynes,w ith a9 9% yield (10:1 E/Z ratio) for diphenylacetylene being obtained within just 1h(1 takes 5h). Similarly,1phenyl-1-propyne fully converts into the anti-Markonikov vinyl phosphine product within 1h.The catalytic activity of 2 with PhCCPh compares favorably with the b-diketiminato calcium amide catalyst DIPP NacNacCa(HMDS)(THF), which required extended reaction times ( Adding ac atalytic amount (30 mol %) of THF to 10 mol %o f1 resulted in hydrophosphination of diphenylacetylene within the same time as that using pre-formed 2, suggesting that deaggregation of dimeric 1 by THF is advantageous in catalysis.A gain, attempted catalysis with unactivated 1-hexyne or 3-hexyne and HPPh 2 by 2 proved unsuccessful. Deaggregation aside,t he coordination shell surrounding ametal cation can play akey role in modulating the Lewis acidity of the metal, thereby providing ap otential route to modify reactivity.Thus,weexplored the effect of the Lewis donor on hydrophosphination of PhC CPh (Table 2). Ar ange of Lewis donor additives were added to the hydrophosphination reactions of diphenylacetylene catalyzed by 1.Adding either two equiv (with respect to the catalyst) of  bidentate donor TMEDA( N,N,N',N'-tetramethylethylenediamine) or one equiv of 12-crown-4 result in quantitative conversions in 1h,the same time as when 3equiv of THF are used. Them olecular structure of the organometallic compound in the presence of polydentate 12-crown-4 was determined via X-ray crystallography as the contact ion pair structure,i Bu 3 AlPPh 2 Li(12-crown-4), with the phosphorus atom bridging the Al and Li centers (Supporting Information). Unfortunately,owing to poor-quality data no geometric parameters can be discussed, however the structure provides unequivocal proof of atomic connectivity.T he use of isolated iBu 3 AlHLi(PMDETA) also results in quantitative product formation within 1h (tridentate PMDETA = N,N,N',N''N''pentamethyldiethylenetriamine).This complex was crystallographically characterized (Figure 2), but all organic ligands exhibit significant disorder which precludes ad iscussion of geometric parameters beyond atomic connectivity. Interestingly,t he E/Z-isomer ratio is dependent on the donor used. PMDETAand 12-crown-4 are less selective (E/Z 2:1; and 5:1respectively,versus 10:1 with 3THF), whereas 2 TMEDAd onors result in enhanced E/Z-selectivity of 19:1. Adding one equiv of bulky tetradentate Me 6 -TREN,takes 3h for quantitative conversion (E/Z 10:1). Adding two equiv of bidentate dppe (diphenylphosphinoethane) results in conversion in 5h,a lbeit with good E/Z selectivity (16:1). Interestingly it appears that when two bidentate donors are added, TMEDAordppe,marked improvements in selectivity occur. Finally,a dding three equiv of PPh 3 to preformed 2 results in both slower catalysis (1.5 h) and poorer selectivity (E/Z 4:1) than those observed with the THF variant, indicating the phosphine Lewis donor may inhibit the hydrophosphination process.
Next, the more challenging hydrophosphination of alkenes was examined using 2 (Table 1). Styrene undergoes hydrophosphination in 6h,a t1 10 8 8C, yielding 84 %o ft he anti-Markovnikov product. Halo-substituted styrenes are also tolerated (Table 1, entries e,f). 4-Vinyl anisole undergoes hydrophosphination to the alkyl phosphine product in 87 % yield after 20 hat110 8 8C. Bulkier substrates such as a-methyl styrene, trans-b-methyl styrene,and the less activated alkene 1-hexene did not undergo hydrophosphination with 2 as the catalyst. Similar failures with both Ca and Sn based catalysts have been noted for these substrates. [6c, 7b] Hydrophosphination of vinyl boronic acid pinacol ester (vinyl Bpin) achieved a9 3% yield after 4h at 110 8 8C, producing linear phosphine boronic ester Ph 2 P(CH 2 ) 2 Bpin. To our knowledge this is the first time Ph 2 P(CH 2 ) 2 Bpin has been made by ahydrophosphination route,since earlier published methods required hydroboration of diphenyl vinyl phosphine. [16] Phosphidoaluminate 2 is also an able catalyst for hydrophosphination of carbodiimides at room temperature.T hus, using 5mol %catalyst loading (Table 1, entries i-j), diisopropylcarbodiimide is converted fully into the phosphaguanidine product within 15 min, while bulkier dicyclohexylcarbodiimide required 20 ht oa chieve 86 %c onversion. Hill reports quantitative yields for diisopropyl and dicyclohexyl carbodiimides within 1h and 4h,r espectively,u sing 2mol %C a-(HMDS) 2 as catalyst, also at room temperature.Significantly longer reaction times were seen when using DIPP NacNacCa-(HMDS)(THF) as ac atalyst (1.5 mol %; iPr, 6h,9 9%:C y, 28 h, 85 %). [6d] KHMDS is also found to be agood catalyst for carbodiimides requiring low catalyst loadings and short reaction times, [6a] while as odium magnesiate also catalyzes hydrophosphination of carbodiimides. [6f] Attempting to pinpoint the active catalyst, four compounds,LiPPh 2 (3), iBu 3 Al (4), iBu 2 AlH (5), and iBu 2 AlPPh 2 (6), [17] were screened for catalytic viability using PhCCH as amodel substrate (Table 1). Using LiPPh 2 as acatalyst yields 86 %c onversion to the vinyl phosphine after 20 h, with anti-Markovnikov regioselectivity,similar to that of 2.Compounds 4-6 afford different product regio-and stereoselectivities as well as lower yields for PhCCH hydrophosphination. Interestingly when 4 is used as catalyst (72 %; 1:8:8 E/Z/a) the major isomer products are the Z-anti-Markovnikov isomer,a nd equally the Markovnikov (a-isomer;P h-(Ph 2 P)C = CH 2 ). In contrast, 2 does not give any appreciable a-isomer, suggesting 2 is not disproportionating in solution at high temperature into LiPPh 2 and iBu 3 Al. To ascertain whether LiPPh 2 is implicated in the catalytic profile,w e conducted another stoichiometric reaction (Supporting Information). Monitoring the reaction of 2 and PhCCPh in   Since after the facile room temperature deprotonation step,alkyne insertion and protonolysis are the other key steps, we performed ad euterium labeling study to investigate the cycle further. Catalytic hydrophosphination between PhC CPh and DPPh 2 favored formation of the E-stereoisomer and deuterium was incorporated into the vinyl phosphine product, Ph(Ph 2 P)C = C(D)Ph, as confirmed by 2 HNMR spectra and GC-MS (Supporting Information). Also,i nas toichiometric reaction between [iBu 3 AlHLi] 2 and DPPh 2 ,HDwas detected in the 1 HNMR spectrum (triplet at d = 4.45 ppm, 1 J = 42.8 Hz), confirming the initial deprotonation step.
Akinetic isotope effect experiment (KIE) was conducted for the hydrophosphination of diphenylacetylene by recording the reaction profile in duplicate for HPPh 2 and DPPh 2 at 100 8 8C, in [D 8 ]toluene,with 10 mol %of2.Bymonitoring the consumption rate of phosphine by 31 PNMR, rates were obtained, and in each case the overall reaction rate is pseudo first order.F rom these rates aK IE of 1.38 AE 0.13 was determined (Supporting Information). This is as mall value, compared with previous reports,and suggests that cleavage of the P À Hb ond is only involved to am inor extent in the rate determining step. [7b] This also indicates that alkyne insertion into 2 is rate-determining,w hich given the rather congested structure of 2 and bulky nature of the alkyne is unsurprising.
Next, we conducted akinetic analysis of the reaction using the variable time normalization analysis (VTNA) method reported by BurØs, allowing us to obtain valuable mechanistic detail under synthetically relevant conditions to three halflives ( Figure 3a nd the Supporting Information). [18] The reaction order with respect to [catalyst] was determined by conducting reactions using different catalyst concentrations, while keeping [alkyne] and [phosphine] constant. These data showed the reaction rate increases with increasing [catalyst], and that the order in catalyst is one.T his situation is consistent with the reaction proceeding via amonomeric rate determining step during the reaction. Va riation of [phosphine] under synthetically relevant conditions revealed that increasing concentration of phosphine inhibits the reaction, giving ap hosphine order of À1. This inhibition likely results from pre-coordination of the phosphine,b locking off the alkyne for insertion. Also,w eh ave already established that bulky mono-and bidentate phosphines slow down reactivity in our Lewis donor study (see above). Lastly,v ariation of [alkyne] revealed af irst order dependence in [alkyne], indicating that the alkyne is involved in the rate-limiting step.
Finally,toreinforce our experimental insight, we turned to DFT calculations.R un on the full system with the internal Scheme 1. Proposed reaction mechanism for hydrophosphination of diphenylacetylene by pre-catalyst 1,s howing formation of active species 2. alkyne,d iphenylacetylene,u sed as the model substrate,t he calculations were performed at the B3LYP-D3/ [19] 6-311G-(d,p) [20] level of theory employing ac ontinuum solvent with the dielectric constant of toluene within the IEFPCM model. [21] Ther elative stability of the formation of 2 from [iBu 3 AlHLi] 2 with 2HPPh 2 and 6THF molecules was initially investigated. Formation of the catalyst (2)i st hermodynamically favorable despite the entropic penalty associated with THF coordination, with ac alculated DG = À63.8 kcal mol À1 (DH = À130.8 kcal mol À1 ). Thea ctivation barrier for the formation of the catalyst was challenging to isolate as aresult of the complex potential energy surface associated with the large dimer species.H owever,abond scan along the coordinate associated with the formation of H 2 provided an indicative barrier (DE*) of about 38 kcal mol À1 ,which would be achievable under the reaction conditions and lead irreversibly to 2 given the exothermic nature of this step.I n contrast to the induction step,t he first step in the catalytic cycle (adding diphenylacetylene to 2)ismildly endergonic for both the E and Z isomers of the intermediate shown in Scheme 1. However,t he E isomer is more stable in the intermediate state of the reaction (DG = 6.9 kcal mol À1 ), with the Z-isomer (DG = 8.3 kcal mol À1 )being further destabilized by 1.4 kcal mol À1 relative to the E-isomer.F inally,generation of the product and reformation of the catalytic species occurs in an exergonic reaction. In this step,the formation of the Zisomer (DG = À25.3 kcal mol À1 )isfavored over the E-isomer (DG = À20.4 kcal mol À1 ). Ther eversal of the relative stabilities of the isomers in the intermediate state versus the product state suggests that the formation of the intermediate is deterministic for the final product distribution, which favors the experimentally determined E-isomer.T he rate-limiting step for the reaction could not be located as the calculation of transition states proved elusive for these bulky compounds. However,t he relative stabilities of the intermediates and products determined for this pathway indicate that the mechanism proposed is achievable under the reaction conditions employed.

Conclusion
Previously lithium aluminates have been shown to be active catalysts for hydroboration of aldehydes,k etones, imines,a nd acetylenes.T his new study extends the catalytic chemistry of these bimetallic main-group compounds by reporting the first example of Al-catalyzed hydrophosphination of alkynes,alkenes,and carbodiimides,using the lithium aluminate (pre)catalyst [iBu 3 AlHLi] 2 .Amechanism is proposed for the alkyne catalysis,e lucidated by stoichiometric reactions,t hought to proceed via formation of the crystallographically defined lithium aluminum phosphide, iBu 3 AlPPh 2 Li(THF) 3 (2), followed by insertion of the alkyne into the Al À Pbond, then protonolysis of asecond equiv of the phosphine to generate the vinylphosphine product and regenerate the catalyst. While intuitively the formation of an anionic aluminum center saturated by four anionic ligands as in an aluminate might be expected to have insufficient Lewis acidity to engage in hydrophosphination processes,itis clear from the different results obtained using an umber of Lewis donor solvent molecules that the presence of the lithium helps to circumvent this apparent handicap so pointing to bimetallic synergistic behavior.

Experimental Section
Full experimental characterization and synthetic procedures are described in the SupportingI nformation.
Synthesis of iBu 3 AlPPh 2 Li(THF) 3 (2): Method (a):H PPh 2 (0.34 mL;2mmol) was added to as tirred solution of [iBu 3 AlHLi] 2 (0.412 g; 1mmol) in hexane (10 mL) and the reaction stirred 1h.THF (0.5 mL;6mmol) was added and then the volatiles were removed. Ther esidue was taken up in hexane (5 mL) and toluene (1 mL). Subsequent cooling to À30 8 8Cy ielded the desired product as paleyellow crystals.C rystalline yield 0.494 g; 0.82 mmol;4 1%. Method (b):n BuLi (0.63 mL;1 .6 m/hexane;1mmol) was added dropwise to as tirred solution of HPPh 2 (0.17 mL;1mmol) in hexane (5 mL) and the resulting bright yellow suspensionstirred for 1h.Addition of iBu 3 Al (1 mL;1 m/hexane; 1mmol) generated ac lear pale-yellow solution, which was stirred for 1h.THF (0.3 mL;3mmol) was added and the pale-yellow solution cooled at General catalytic reaction:T he desired catalyst loading was added to 0.5 mL of [D 8 ]toluene solution (unless alternative solvent specified) containing the substrate precursor (0.6 mmol) and HPPh 2 (0.5 mmol, 0.09 mL). Thereaction mixture was transferredtoasealed J. Youngstap NMR tube and the reaction was regularly monitored by 1 Hand 31 PNMR spectroscopy until the formation of the products was completed as determinedb yi ntegrationv ersus an internal capillary standard (hexamethylcyclotrisiloxane). Fora lkynes and alkenes,t he hydrophosphination catalysis was performedat110 8 8Cwith 10 mol % [Al] catalyst loading.F or carbodiimides the hydrophosphination catalysis was performed at room temperature with 5mol %[ Al] catalyst loading.T he yields reported are based on 1 HNMR and 31 P relative to the internal standard. In all cases,t he bulk of the NMR solution can be attributedt oe ither product compounds or starting materials. Yields of isolated product are provided for example substrates, isolated via either recrystallization methods or column chromatography,a sreported in the Supporting Information.