Phosphines asymmetric hydrophosphination

Similar catalytic reactions allowed stereocontrol at either of the olefin carbons (Scheme 5-13, Eqs. 2 and 3). As in related catalysis with achiral diphosphine ligands (Scheme 5-7), these reactions proceeded more quickly for smaller phosphine substrates. These processes are not yet synthetically useful, since the enantiomeric excesses (ee s) were low (0-27%) and selectivity for the illustrated phosphine products ranged from 60 to 100%. However, this work demonstrated that asymmetric hydrophosphination can produce non-racemic chiral phosphines [13]. 

Asymmetric hydrophosphination has been utilized as a route for preparing chiral phosphines. The Pt° complex [(Me-DUPHOS)Pt(t/ tf/ ,s-PhCII ClIPh)] (73) brings about the catalytic P-H addition of bulky secondary phosphines to activated alkenes with modest enantioselectivity. The most promising substrate combinations for further development appear to be bulky alkenes and less bulky phosphines (Scheme 46).195... 

Kovacik, I., Wicht, D.K., Grewal, N.S., Glueck, D.S., Incarvito, C.D., Guzei, I.A., and Rheingold, A.L., Pt(Me-Duphos)-catalyzed asymmetric hydrophosphination of activated olefins enantioselective synthesis of chiral phosphines,... 

The mechanistic study on the hydrophosphination of activated olefins, in conjunction with rapid inversion of the configuration at the phosphorus center, was elaborated to develop asymmetric hydrophosphination catalyzed by a chiral phosphine platinum complex although the % ee is not excitingly high yet (Scheme 9) [15]. 

Although no mechanism was proposed, the Pd(Me-DuPhos)-catalyzed asymmetric hydrophosphination of an alkyne with a phosphine-borane under kinetic resolution conditions (Scheme 6) presumably involves similar insertion and reductive elimination steps [14]. 

In 2007, Glueck s group reported a catalytic DKR process in which secondary phosphines were converted into the corresponding enantio-enriched tertiary phosphines through palladium-catalysed asymmetric hydrophosphination of aryliodides using secondary phosphines. The key intermediates were diaster-eomeric phosphide complexes with chiral ancillary ligands (L Pd PRR ). Their relative rates of P-inversion and phosphorus-carbon bond formation controlled the enantioselectivity of the prodnct formation. As shown in Scheme 2.63, the reaction allowed moderate enantioselectivities of up to 70% ee to be achieved. 

Chiral metallacycles have been employed as auxiliaries for the promotion and control of asymmetric reactions such as Diels-Alder cycloadditions involving phospholes [19]. This synthetic methodology can be extended to the synthesis of diphosphine motifs via asymmetric hydrophosphination of vinylic and other tmsat-urated phosphine-functionalized substrates. The advantages offered by these metal complexes are listed below ... 

Scheme 7 Asymmetric hydrophosphination of phosphine functionalized alkenols...

The asymmetric hydrophosphination of the cyano-functionalized phosphine has also been undertaken in view of the potential for further manipulation of the cyano moiety to formyl and hydroxyl functionalities [58]. This will serve as an elegant method for accessing these functionalized diphosphines. The diastereoselective hydrophosphination reactions of the c -cyano-functionalized phosphine complex ( = 1) gave the chiral l,2-bis(diphosphino)ethane products in high yield (90%) and stereoselectivity S isomer formed exclusively). For the trans analogue, the absolute stereoselectivity was 10 1 with the S isomer being the major product. 

The flexibility and potential of this chiral auxiliary continues to show scope for expansion, and recently they have proven to be extremely efficient in certain catalytic versions of the asymmetric P-H addition process (Table 1) [80]. Very few catalytic asymmetric syntheses of chiral tertiary phosphines by hydrophosphination have been... 

Apart from being air sensitive, the generally stable M-P coordination renders technical difficulties in the elimination of the tertiary phosphine product in catalytic process involving transition metal ions as catalysts. However, the asymmetric hydrophosphination of aromatic enones could be catalyzed by the same organo-palladium (II) complex with high yields and stereoselectivity (Table 1). 

In summary, asymmetric P-H additions leading to the direct enantioselective/ diastereoselective formation of optically pure mono- and polydentate tertiary phosphines are thus a field that has more room for development. This is true especially in the realm of catalytic P-H additions as illustrated in the preceding sections wherein design of better catalysts is currently attracting much attention. It is thus foreseeable that in the near future even more types of enantiomericaUy pure tertiary phosphines with a large range of functionality will be soon available via the asymmetric hydrophosphination reaction. 

Simultaneous publication of the iminium ion catalysed hydrophosphination of a,p-unsaturated aldehydes by Melchiorre and Cordova showed diarylprolinol silyl ether 55 was effective in the conjugate addition of diphenylphosphine 74 [117, 118], Direct transformation of the products allowed for one-pot methods for the preparation of P-phosphine alcohols 75 (72-85% yield 90-98% ee), P-phosphine oxide acids 76 (65% yield 92% ee) and 3-amino phosphines 77 (71% yield 87% ee) (Scheme 34). These reports represent the first examples of the addition of P-centred nucleophiles and the resulting highly functionalised products may well have further use in asymmetric catalysis. 

Organolanthanide complexes are known to be highly active catalysts for a variety of organic transformations, which can be either intramolecular or intermolecular in character. Successful intramolecular transformations include hydroelementation processes, which is the addition of a H-E (E = N, O, P, Si, S, H) bond across unsaturated C-C bonds, such as hydroamination, hydroalkoxylation, and hydrophosphination. Intermolecular transformations include a series of asymmetric syntheses, the amidation of aldehydes with amines, Tishchenko reaction, addition of amines to nitriles, aUcyne dimerization, and guanylation of terminal aUcynes, amines, and phosphines with carbodiimides. 

Busacca and co-workers have prepared menthol-derived phosphinite boranes 101 and 102, by direct addition of anionic secondary phosphine borane 100 to carbodiimides, yielding the chiral phosphinite boranes under ambient temperature conditions (Scheme 25). These and other derivatives, prepared by hydrophosphination of carbodiimides, were used in the synthesis of enantiomerically enriched phosphaguanidines with potential use as ligands in asymmetric catalysis. 

In tenns of understanding the mechanistic aspects involved in such additimis on vinylic substrates via organometallic catalysts, analogies have been drawn to the hydroamination reactimis [28-30], Chiral metal complex-promoted asymmetric hydroaminations have been proposed to follow two different pathways. The first involves a sequence that commences with the oxidative addition of the N-H bond onto the metal ion followed by the insertion of the olefin and subsequent reductive elimination of the chiral substrate. An alternative pathway has also been proposed which involves the nucleophilic attack by the free amine on a coordinated olefin and a final protonolysis sequence, which leads to the release of the final product. Similar studies on metal irm-induced hydrophosphinations have been reported, and the mechanisms suspected to be in play include those proposed by Glueck and coworkers which basically involves the oxidative addition of a secondary phosphine followed by an olefin insertion [31], Togni and coworkers have also observed in certain scenarios the coordination of the olefin to the catalyst metal center followed by the addition of a secondary phosphine across the C-C double bond [32]. 

One of the first functionalized substrates subjected to the asymmetric P-H addition promoted by metal complexes were phosphine-functionalized alkenols, viz., 3-diphenylphosphinobut-3-en-l-ol and 2-diphenylphosphinoprop-2-en-l-ol (Scheme 7) [54]. The target was the diphosphine ProPhos which had previously been prepared by tedious organic manipulations extending to 14 steps from a chiral pool consisting of malic and L-ascorbic acid [55, 56]. The hydrophosphination reaction employing (/ )- was carried out as shown in scheme 7 and showed excellent selectivity in the case of 3-diphenylphosphinobut-3-en-l-ol (four isomeric products in the ratio 2 18 1 4) and moderate selectivity in the case of 2-diphenyl-phosphino prop-2-en-l-ol (1 2 5 8). Isomer 12a was the major product in the case of 3-diphenylphosphinobut-3-en-l-ol (n = 1), and for 2-diphenylphosphinoprop-2-en-l-ol (n = 2), 11a and 11b co-crystallized out. The two analogous substrates gave products that differ in the chirality at the newly formed carbon center. 

Glueck et al. have reported the addition reaction to activated alkenes (Michael acceptors) and have carried out detailed mechanistic studied [121,122]. An important mechanistic study was also carried out for the palladium catalyzed asymmetric phosphination [123, 124]. Hydrophosphination of less activated olefins was achieved for the first time by Ni-catalyzed reaction using phosphite ligands (Scheme 8.44) [125],... 

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