MiniPHOS diphosphines

The very good results of BisP ligands in several catalytic reactions prompted Yamanoi and Imamoto to simplify even further their structure but maintain 

The enantioselective deprotonation protocol has been found to be well suited for the preparation of dendrimers, macrocycles, polyphosphines and polymers containing P-stereogenic atoms. To date, most of the reported compounds are derived from t-Bu-BisP.  

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.  

Deprotonation of t-Bu-BisP (BH3)2 with 1.2 equivalents of s-BuLi/( )-sparteine formed a mixture of mono- and dilithiated t-Bu-BisP (BH3)2 whose - intermolecular oxidative coupling with Cu(II) afforded a mixture of tetraphosphine borane 86 and hexaphosphine borane 87. The use of ( )-sparteine may surprise the reader, as the reaction does not involve any enantioselective deprotonation. However, it was found that its presence was beneficial to activate the -BuLi, showing that ( )-sp is not only a chiral inductor, but also modifies the reactivity of the organolithium reagents. After separation by column chromatography, 86 and 87 were obtained in 26% and 14% isolated yields respectively. Tetraphosphine borane 86 was subjected to similar reactions, affording compounds 88 (29% yield) and 90 (8% yield), which contain 8 

90 present a characteristic Tg. Hexaphosphine 87 exhibits an interesting intermediate behaviour between a crystalline small molecule and an amorphous polymer. It presents crystalline and amorphous states and therefore constitutes an example of an amorphous small molecule, a so-called molecular glass.  

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Table 5.16 MiniPHOS diphosphine boranes reported to date (Scheme 5.34).

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... 

We further synthesized unsymmetrical MiniPHOS derivatives 13b (Scheme 13) [30]. Thus, enantioselective deprotonation of l-adamantyl(dimethyl)phos-phine-borane (74, R = 1 -Ad), followed by treatment with ferf-butyldichlorophos-phine or 1-adamantyldichlorophosphine, methylmagnesium bromide and bo-rane-THF complex afforded the optically active diphosphine-boranes 82b as a mixture with the corresponding raeso-diastereomer. Enantiomerically pure unsymmetrical MiniPHOS-boranes 82b were obtained by column chromatography on silica gel or separation by recycling preparative HPLC. 

The borane group of MiniPHOS was removed using the same protocol (Scheme 21). In contrast, however, reaction of free diphosphines 13 with [Rh(nbd)2]+X (X=Bp4, PFg) afforded in all cases, and independently of the reaction conditions, bischelate complexes 106. James and Mahajan demonstrated... 

The first example for the use of a diphosphine bearing stereogenic phosphorus atoms as a ligand in copper-catalyzed Michael additions has been reported by Inamoto and co-workers,265,265a who showed that the reaction of cyclohex-2-enone and the corresponding seven-membered enone with diethylzinc in the presence of Cu(OTf)2 and 307 (abbreviated as MiniPHOS) gave rise to the formation of the addition products with 70% and 97% ee, respectively (Scheme 84). The corresponding transformation of chalcone proceeded with 71% ee. Other simple diphosphines, however, displayed only moderate enantioselectivities in copper-catalyzed Michael additions.226... 

The trimethylsilyl derivative 109 was chosen because its optical purity can be easily increased by recrystallisation until a virtually enantiopure compound is obtained in 56% yield. Some screening showed that polyamines such as PMDETA in combination with. s-BuLi constitute the optimum conditions in order to minimise undesired functionalisation of the methylene group. Under these conditions, 109 was regioselectively lithiated and the carbanion further elaborated by known methods to afford, after a standard desilylation step, a-hydroxyphosphine sulfide 110 (55% yield, 94% ee) and p-hydroxyphosphine sulfide 111 (50% yield over two steps, 96% ee). The method was also adapted to yield diphosphine sulfides 112 (69% yield, 90% ee) and 113 (46% yield, 99% ee). The latter compound is indeed the disulfide of (5, 5)-t-Bu-MiniPHOS. During its synthesis it was observed that no meso compound was formed. 

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. 

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