BisP Diphosphines

The desired phosphine boranes were prepared from phosphorus trichloride in a few steps using inexpensive materials. Although the diastereoselectivities were not very high, particularly in the phosphine of entry 5, the meso-68 compounds could be efficiently separated by conventional methods (chromatography or recrystallisation) affording chemically pure C2 compounds. Their optical purities could be easily increased by recrystallisation because the meso isomers were found to be more soluble than the C2 counterparts with the exception of the compound in entry 1. It has to be said that 68 could not be deboronated by the classic treatment with amines and the acidic method had to be used (see Chapter 1, Section 1.3.2).  

All the ligands bear the smallest alkyl group, methyl, and a bulky alkyl group. Upon coordination to transition metals, they form five-membered 

C2-symmetric rings with a strong steric dissymmetry, which proved to be exceptionally beneficial for catalytic performance, especially in hydrogenation reactions. The downside is that due to their trialkyl nature, the ligands are very electron-donating and therefore extremely sensitive to oxidation. 

The practical unavailability of (+)-sparteine means that the standard enantioselective deprotonation protocol can not be used to prepare (i ,f )-BisP diphosphines (see, however. Section 5.4.1). Some work has been performed to overcome this limitation. Imamoto and co-workers were able to prepare both enantiomers of t-Bu-BisP (BH3)2 by using both enantiomers of mrt-butyl-methylphosphine borane. Unfortunately, the preparation of the latter compounds involved a preparative HPLC separation step and therefore the strategy cannot be easily adapted for large-scale synthesis. 

Deboronation of (S , S)-t-Bu-BisP (BH3)2 and consequent oxidation easily provides (i ,i )-t-Bu-BisP (0)2. Both steps occur with retention of configuration the change in the descriptors of the absolute configuration merely agrees with the priority order in the CIP rules. This oxide was then stereo-selectively reduced and reboronated with a procedure known to provide inverted products (see Chapter 1, Section 1.3.1). Although the desired eom-pound was obtained in optically pure form, the yield was disappointingly low (24%). 

---

Scheme 5.28 Preparation of BisP diphosphine boranes from PCI3.

Scheme 5.32 Preparation of unsymmetric BisP diphosphine boranes (75).

Table 5.14 BisP diphosphine boranes reported to date (Scheme 5.28).

Scheme 5.33 Preparation of uns5mmetric BisP diphosphine boranes with a single...

The diboronated BisP diphosphines contain two methyl groups amenable to be deprotonated and oxidatively oligomerised to afford C2-oligophosphine boranes with an even number of phosphorus atoms. This chemistry has been extensively studied by Chujo and co-workers (Scheme 5.37). ... 

Chujo and co-workers" " have also described several copolymers containing (5 ,[Pg.267]

As mentioned in Sect. 2.2, phosphine oxides are air-stable compounds, making their use in the field of asymmetric catalysis convenient. Moreover, they present electronic properties very different from the corresponding free phosphines and thus may be employed in different types of enantioselective reactions, m-Chloroperbenzoic acid (m-CPBA) has been showed to be a powerful reagent for the stereospecific oxidation of enantiomerically pure P-chirogenic phos-phine-boranes [98], affording R,R)-97 from Ad-BisP 6 (Scheme 18) [99]. The synthesis of R,R)-98 and (S,S)-99, which possess a f-Bu substituent, differs from the precedent in that deboranation precedes oxidation with hydrogen peroxide to yield the corresponding enantiomerically pure diphosphine oxides (Scheme 18) [99]. 

The same effect has been observed and studied with the diphosphine tBu-BisP I.D. Gridnev, M. Yasutake,... 

The success of Burk s alkyl diphosphines spurred development of a number of other ligands with electron rich phosphines, such as Zhang s PennPHOS (7) [36-38], Marinetti s /Pr-CnrPHOS (8) [39], and Imamoto s BisP ligands (9) [40],... 

A number of attempts have been made to find an accurate empirical predictor of the sense of product chirality. The twist in the diphosphine chelating ring is one example 8 twists lead to S product while X twists lead to R product [7, 49]. However, ligands such as DuPHOS have no backbone twist. Another predictor is the twist in the coordinated diene of the catalyst precursor catalysts with dienes twisted counterclockwise lead to R products, with clockwise leading to S [50], This works well for most ligands, but fails for BisP, which exhibits a small clockwise twist but produces R product... 

Dihydroboronium derivatives of t-Bu-BisP with different cotmter anions were prepared, as shown in Scheme 56. The reaction of BisP with BH2Br afforded the boronium salt 175 which possessed a bromide ion. The dihydroboronium derivative of (S,S)-l,2-bis(tert-butylmethylphosphino)ethane 175 (t-Bu-BisP ) was prepared by the reaction of t-Bu-BisP 174 with catecholborane and used as chiral diphosphine ligand precursor in Rh-catalyzed asymmetric hydrogenated of methyl (Z)-acetamidocinnamate to afford the hydrogenation product in up to 94% ee. Complexes of iron(III) and P-chiral phosphine oxides 176 are catalysts for the asymmetric Diels-Alder reaction of iV-acrylamide dienophiles [106]. 

The diphosphines discussed in this section are of the same type as those seen in the beginning of Section 5.2.1.2, the only difference being that they do not bear any aromatic substituent, i.e. they are l,2- )w(alkylmethylphosphino)ethanes. They have been proved to be superb in hydrogenation reactions (Chapter 7) and other catalytic transformations (Chapter 8) and form one of the most important types of new generation R-stereogenic ligands. The name BisP was coined when their synthesis was first reported by Imamoto and co-workers. Their preparation consists of the enantioselective deprotonation protocol followed by Cu(II) oxidative coupling (Scheme 5.28 and Table 5.14). 

Deprotonation and electrophilic quenching with Mel alforded (f ,f )-t-Bu-BisP (BH3)2 in quantitative yield as an optically pure product. Other electrophiles also reacted smoothly to yield other diphosphine boranes 72. The interesting cycKc diphosphine borane 73 was obtained in 35-53% yield when the dianion of 71 was treated with CH2CI2. The methylene group bridging the two phosphorus atoms could also be alkylated to afford 74 in 35% yield. 

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). 

First generation dendrimer 82 was obtained in 64% yield after purification by HPLC to remove the monofunctionalised compound, formed in 18% yield. This dendrimer was also prepared in optically inactive form, starting from rac-t-Bu-BisP (BH3)2, in 82% yield. Second generation dendrimer 83 was then prepared similarly in 70% yield after HPLC purification. The diphosphine borane 84 was also prepared in 42% yield to be used as a model." " The optically active dendrimers were analysed by CD measurements and it was found that they exhibited the Cotton effect, induced by the stereogenic phosphorus atoms, in the 280 nm ti-ti absorption band of the aromatic rings. Unexpectedly, compound 84 did not display any Cotton effect." ... 

Entry 3 corresponds to one of the first reports about enantioselective catalytic Michael additions. For 37 the best results are obtained with MiniPHOS diphosphines (entries 7 and 8). In contrast, other diphosphines such as BisP and DrPAMP provide product 39 in low optical purity (entries 10 and 7... 

The electron-rich t-Bu-MiniPHOS ligand provided good yield but moderate enantioselectivity (entry 1). Much better results have been obtained with the related ligand t-Bu-BisP (entry 2) and with the QuinoxP ligands (entries 3-5). The diphosphine of entries 6 and 7, containing an unsubstituted ethynyl group, leads to excellent yields and almost perfect enantioselectivities. 

Formation of solvate dihydrides Experimentally formation of solvate dihydrides has been observed for several Rh-diphosphine catalysts. Thus, two diastereomeric dihydrides 28a, b were obtain via the reversible oxidahve addition of H2 to the solvate complex [Rh(f-Bu-BisP )(CD30D)2]+ (27) and have been characterized by NMR (Scheme 1.9). 

---