Phosphines DIPAMP

The hydrogenation reaction is carried out with a substituted cinnamic acid. The acetamido group is of particular importance because it functions as a secondary complexation function in addition to the alkene functionality. In the first step the alkene co-ordinates to the cationic rhodium species (containing an enantiopure phosphine DIPAMP in Figures 4.4 and 4.5 with the chirality at phosphorus carrying three different substituents, Ph, o-An, CH2) for which there are several diasteromeric structures due to ... 

Of these reactions only I and II-Z and the corresponding ee s work with high efficiency. The best phosphine available to us for these conversions was (fl,fl)-l,2-ethanediylbis-[(2-methoxyphenyl)-phenyl-phosphine](DiPAMP) (3). Since a number of variants of this molecule were readily available from a common, resolved intermediate, it seemed worthwhile to make a few of these with the hope of achieving marginal gains as well as improving our understanding of this remarkable catalysis. Table I shows a number of bisphosphines that were prepared for this study. 

An asymmetric version of the total synthesis of clavicipitic acid was reported by Yokoyama et al. [82-84]. As illustrated in Scheme 29 asymmetric hydrogenation of the known 4-bromodehydrotryptophan 163 was best achieved (94% ee) using the optically active Monsanto bidentate phosphine, DIPAMP. The Heck vinylation in the presence of Ag,CO, gave the C(4)-vinylated product 168 without racemization. Treatment of 168 with HCl-EtOAc effected the cyclization to give the tricyclic azepinoindole 170 (62%), al.- ig with diene 169 (29%). Cleavage of the sulfonamide (Mg/MeOH) afforded 171 which underwent saponification (KOH) to give optically active clavicipitic acid (167). 

Variation of the ligands in the rhodium complex eventually led to the chiral phosphine DIPAMP. 

The numerous chiral phosphine ligands which are available to date [21] can be subclassified into three major categories depending on the location of the chiral center ligands presenting axial chirality (e.g., BINAP 1 and MOP 2), those bearing a chiral carbon-backbone (e.g., DIOP 3, DuPHOS 4), and those bearing the chiral center at the phosphorus atom (e. g., DIPAMP 5, BisP 6), as depicted in Fig. 1. 

Early work in the field of asymmetric hydroboration employed norbornene as a simple unsaturated substrate. A range of chiral-chelating phosphine ligands were probed (DIOP (5), 2,2 -bis(diphenyl-phosphino)-l,l -binaphthyl (BINAP) (6), 2,3-bis(diphenylphosphino)butane (CHIRAPHOS) (7), 2,4-bis(diphenylphosphino)pentane (BDPP) (8), and l,2-(bis(o-methoxyphenyl)(phenyl)phos-phino)ethane) (DIPAMP) (9)) in combination with [Rh(COD)Cl]2 and catecholborane at room temperature (Scheme 8).45 General observations were that enantioselectivities increased as the temperature was lowered below ambient, but that variations of solvent (THF, benzene, or toluene) had little impact. 

The related chiral rhodium catalyst 4 has been used to effect kinetic resolution of these substrates.2 In this catalyst the achiral phosphine ligand of 1 is replaced by (R,R)-l,2-bis(o-anisylphenylphosphino)ethane (DIPAMP). Hydrogenation cat-... 

DIOP contains two sp3 asymmetric carbons. DIPAMP possesses two asymmetric phosphorus atoms. The fully aromatic BINAP ligand possesses only axial chirality (13, 14). Although many phosphine ligands have only P-C bonds, some promising ligands possess P-O or P-N bonds (75). 

A number of chiral bisphosphines related to DiPAMP(l) were prepared and evaluated in asymmetric catalysis. Many variants were closely equivalent but none were superior to the parent compound. In addition, some monophosphines containing sulfone substituents were quite effective. These had the particular advantage of being usable in water solution. Several new DIOP derivatives were tried in the hydroformylation of vinyl acetate but only modest enantiomeric excesses were achieved. A 72% enantiomeric excess was achieved on dehydrovaline under relatively forcing conditions using DiCAMP(3). This result was remarkable since these phosphine ligands generally work very poorly, if at all, on tetrasubstituted olefins. 

Phosphine 12 was prepared by cleaving the methyl ether on DiPAMP with lithium diphenylphosphide in tetrahydrofuran (THF) at ambient temperatures. 

Three types of experiments have proved informative in the mechanistic study of asymmetric hydrogenation. These are, respectively, rate measurements and product analysis, X-ray crystallography and NMR-derived identification of stable and transient species involved in the catalytic cycle. The first two of these have been reviewed elsewhere (2, 3, 4) our own work has been concerned with NMR and has provided a surprising wealth of structural and mechanistic detail. A variety of chiral phosphine procatalysts have been used but the current discussion will be concerned largely with two. Thus (R,R)-1,2-ethanediylbis-[(2-methoxyphenyl)phenylphosphine] (1) (DiPAMP)... 

Asymmetric hydroboration of prochiral alkenes has been achieved using transition metal catalysts and chiral phosphines as ligands to obtain enantiomerically pure alkyl boronates <1997CC173>. Catalysts such as Rh(COD)2+BF4 , Rh(COD)2+Cl, Rh+BF4 , etc., in combination with chiral phosphines like DIOP 71, BINAP 72, CHIRAPHOS 73, DIPAMP 74, BDPP 75, ferrocene-based diphosphines 76<1999TL4977>, etc., have been employed for the asymmetric hydroboration of prochiral alkenes with moderate to high ee (DIOP = 2,3-0-isopropylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane BINAP = 2,2-bis(diphenyl-phos-phanyl)-l,1-binaphthyl CHIRAPHOS = 2,3-bis(diphenylphosphino)butane DIPAMP = l,2-bis[(2-methoxyphe-nyl)phenylphosphino]ethane BDPP = 2,4-bis(diphenylphosphino)pentane). 

Hydrogenation catalysts. A number of new optically active phosphine ligands have been developed for selective enantioselective reduction of N=C bonds of amino acid precursors, including DPCB(l)1, the methylene homolog (2)2 of dipamp, and the novel ligand 3, in which the source of chirality is a Re atom.5 A ligand 4 has been used as a Rh(I) complex for hydrosilylation.4... 

The catalyst is a cationic complex of rhodium with another diphosphine, DIPAMP. DIPAMP s chirality resides in the two stereogcnic phosphorus atoms unlike amines, phosphines are configurationally stable, rather like sulfoxides (which we will discuss in the next chapter). The catalyst imposes chirality on the hydrogenation by coordinating to both the amide group and the double bond of the substrate. Two diastereoisomeric complexes result, since the chiral catalyst can coordinate to either of the enantiotopic faces of the double bond. 

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