Diop* ligand

The Heck coupling reaction appeared to be a route of choice to achieve the synthesis of the modified-DIOP ligands. We previously studied the palladium-catalyzed coupling of acrolein and acrolein acetals with several polyaromatic and heteroaromatic bromides either in the presence of homogeneous or heterogeneous catalytic systems (6, 7). After optimization of the reaction conditions, high conversions and selectivities were achieved except with anthracenyl derivatives (8). Based on these results, we developed the synthesis of the desired ligands. The... 

This approaeh allows the Ml synthesis of the modified DIOP ligands (Scheme 21.6). Three new hgands were synthesized with 15-20% global yield (6 steps) according to a similar route as described for DIOP synthesis (11). After chemical reduction of the diester to the diol, the mesylated compounds were isolated. Their treatment with diphenylphosphine previously reacted with n-BuLi to yield LiPPh2 gave the expected ligands with 49-55% isolated yield. 

Figure 3 Chiral DIOP ligands for asymmetric hydroboration.

Livinghouse and co-workers report a similar carbocyclization, using a dimethyl malonate diene-ene derivative, in which they obtained 6% ee (69%) with a highly sterically hindered DIOP-based ligand (ref 25). The unaltered DIOP ligand was also highly efficient (83%), but imparted poor enantio-control (10% ee). 

At best, the product has 26% op using zerovalent or divalent palladium complexes of (R,R)-Diop. Ligands which give rise to a more rigid chiral environment around the metal center, e.g., (l/ ,2/ )-bis(diphenylphosphano)cyclopentane, may lead to enhanced enantioselectivity. 

This chapter reports principally on studies with ruthenium chiral phosphine and chiral sulfoxide complexes and their use for catalytic hydrogenation. We have used the familiar diop ligand, [2R,3R-(—)-2,3-Oisopropylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino) butane] (7) a related chiral chelating sulfoxide ligand dios, the bis(methyl sulfinyl)butane analog (21) (S,R S,S)-(+)-2-meth-ylbutyl methyl sulfoxide(MBMSO), chiral in the alkyl group and R-(+)-methyl para-tolyl sulfoxide(MPTSO), chiral at sulfur. Preliminary data on some corresponding Rh(I) complexes are presented also. 

Apparently, the large optically active (— )-diop ligand (58) acts as a template during either the initial tr-coordination step or n—tr-rearrangement step in the mechanism proposed for hydrogenation via a homogeneous catalyst (69). 

Figure 6.13 The DIOP ligand a structure b molecular graph c adjacency matrix. The broken linesindicatetheshortestand longest P-P connectivity paths, Dpi p2 and AP1 P2, respectively. The adjacency matrix of a molecular graph is a matrix with rows and columns labeled by graph vertices v (i.e., the atoms), with a 1 or 0 in position (vp Vj) according to whether Vj or Vj are adjacent or not.

Two matrices are particularly important, both of them based on the topological distance between vertices within a graph the distance matrix D(G) and the detour matrix A(G). The first contains as values the smallest number of steps from vertex i to vertex j, and the second contains as values the longest paths. For example, Equation (6.5) shows the D and A matrices of the DIOP ligand. 

The Rh/Diop catalytic system is one of the fastest catalyzed gas-liquid asymmetric hydrogenations. A (R,S)-Cy-Cy-Josiphos ligand behaves almost as good as the Diop ligand and provides abetter enantioselectivity of 75% (Josiphos family of ferrocenyl diphosphine ligands cy cyclohexyl). The latter is the most active of the Josiphos family (88% conversion). The reproducibility of the data obtained has been checked with the Rh/Diop catalytic system. For more than five tests, the mean deviation was 2% for conversions and less than 1% for the enantiomeric excess that proved the reliability of this new microdevice. 

The first example of a chiral copper photosensitizer is [Cu(dmp)((R,R-diop))]+ [R,R-diop = (R,R)-2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis(diphe-nylphosphino)-butane dmp = 2,9-dimethyl-1,10-phenanthroline], in which two chiral centers are introduced in the (R,R)-diop ligand. This complex was applied to the stereoselective photoreduction of [Co(edta)]- [25]. After the reaction, the CD spectrum exhibits a positive peak at 590 nm and a negative one at 515 nm, which indicates the presence of excess A-fCo(edta)]. This means that A-[Co(edta)] more rapidly reacts with the photoexcited copper complex than does the A-enantiomer, where the stereoselectivity, defined as the ratio of the conversion rate, is 1.17. However, the photoreduction of Co(acac)3 and [Co(bpy)3]3+ occurs without stereoselectivity. This is probably because the electrostatic attraction between [Cu(dmp)((R,R-diop))]+ and [Co(edta)] is favorable for the stereoselection, but such interaction does not exist between [Cu(dmp)((R,R-diop))]+ and the other cobalt(III) complexes. 

The isolation of a series of iridium(I) complexes with the optically-active diop ligand (46) [diop = 4,5-bis(diphenylphosphinomethyl)-2,2-dimethyl-l,3-dioxolane] has been reported. Equivalent portions of diop and [Ir(Cl)(cod)]2 in ethanol yield [Ir(Cl)(diop)(cod)] EtOH.126 The X-ray crystal structure of this complex shows a distorted trigonal bipyramid in which diop serves as an apical-equatorial bidentate ligand. The structure is maintained in solution, as evidenced by 31P NMR data in CDC13 at 223 K.127 In acetone solution, reaction between [Ir(Cl)(cod)]2 and two or more equivalents of diop affords [Ir(diop)2](BPh4), which reacts with CO to yield [Ir2(CO)2(diop)3](BPh4)2.126... 

Application of this cyclization reaction to a large variety of 4-pentenals with the aid of the rhodium complex has been reported. The first example of an asymmetric cyclization of 4-pentenals via hydro acylation using a chiral rhodium diphosphine catalyst was published by Sakaki et al. in 1989 [ 104]. The diphosphine ligand ((lS,2S)-rraws-l,2-bis(diphenylphosphinomethyl)cyclohexane) having a cyclohexane backbone in the chiral center shows the better asymmetric induction than DIOP ligand. Various types of enals are applicable to this asymmetric intramolecular hydro acylation reaction [105,106]. The use of BINAP ligand as the chiral auxiliary improves the optical yield to >99% ee when 4-substituted 4-pentenals are used as the substrate (Eq. 49) [106]. Steric repulsion between the substituent at the 4-position and the substituent on the phosphine atom controls the enantiofacial selection. 

Considering that a metal DIOP complex is conformationally fiexible and the stereo genic centers may be too far from the substrate, Kagan synthesized a modified DIOP ligand 28 in which the stereogenic centers are closer to the phosphorus atom [31]. 

The very high enantioselectivity of the hydrogenation of the 1-benzyl intermediate, even with the conventional MOD-DIOP ligand was probably the most impressive result. Development of the process with the N-l benzyl substituent would have made the later intermediates of the biotin process identical to those in the existent commercial process, which could have expanded the market opportunities... 

Recently, the attractive direct enantioselective hydrogenation of 6 to (S)-7 has met with some success. Thus, the Lonza group showed that the dihydrogen phosphate salt of the chemically rather labile imine 6 can be hydrogenated with Ir-fer-rocenyldiphosphine catalysts in a two-phase solvent system with up to 89% ee (Table 2, entry 3) [12]. Similar results were achieved in our laboratories with the hydrogen sulfate salt of 6 and an Ir catalyst derived from a sterically bulky f-Bu-DIOP ligand in a monophasic solvent system (Table 1, entry 4) [13]. Chemose-... 

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