Ligand substrate ratio

To our knowledge, the first published report of a photocatal-ytic reaction at elevated pressure was W. Strohmeyer1s hydrogenation of 1,3-cyclohexadiene under hydrogen at 10 atm /22/. On photolysis, the iridium complex 8 formed a very active catalyst, probably by dissociation of a phosphine ligand (Equation 17). At 70 C, with hydrogen at 10 atm, and a catalyst/substrate ratio of 1/100,000, the activity was 196 per minute and the turnover number was 96,000 mol of product/mol catalyst. 

No catalyst has an infinite lifetime. The accepted view of a catalytic cycle is that it proceeds via a series of reactive species, be they transient transition state type structures or relatively more stable intermediates. Reaction of such intermediates with either excess ligand or substrate can give rise to very stable complexes that are kinetically incompetent of sustaining catalysis. The textbook example of this is triphenylphosphine modified rhodium hydroformylation, where a plot of activity versus ligand metal ratio shows the classical volcano plot whereby activity reaches a peak at a certain ratio but then falls off rapidly in the presence of excess phosphine, see Figure... 

Ligand Substrate SIC ratio Reaction conditions Percent ee of product (confign.) References... 

Ligand Substrate S/C ratio Reaction conditions % ee (config.) Ref. 

The matching and mismatching of chiral olefin 54 and catalyst was examined briefly by using stoichiometric quantities of osmium tetroxide with achiral and chiral ligands [60], The monothio acetal derived from camphor (54) was dihydroxylated with osmium tetroxide in the presence of quinuclidine, DHQD-OAc, or DHQ-OAc, With the achiral quinuclidine as ligand, the ratio of (2S,3R) to (2R,3S) diasteriomers 55 and 56 was 2.5 1. With DHQD-OAc as the chiral ligand, catalyst and substrate are matched and the ratio is enhanced to 40 1 while with DHQ-OAc catalyst and substrate are mismatched and a reversed selectivity of 1 16 is observed. 

Substrate Chiral ligand Metal- to-ligand molar ratio Reaction conditions Con- versionh Yield Hydroformylation product and isomeric composition1 Chiral reaction product Ref. 

Table 1-12. Effects of ligand (L) and substrate ratios on the coupling between phenyl triflate and ( )-l-methoxy-l-(trimethylsiloxy)propene (L = phosphine ligand) (data from [165])...

It is very important to stress that the large parameter space in homogeneous catalysis is not represented by the number of metal-ligand combinations alone. To discover a cost-effective scalable process for many transformations, many other parameters have to be considered and optimized. For example, consider the choice of the following important reaction parameters for a given transformation four different ligand/metal ratios, four different pressures, three different substrate/metal ratios, three different solvents, and two different temperatures. The inclusion of these parameters into a HT screen will result in almost 300 experiments for each metal-ligand combination ... 

The optimal Nirligand ratio appears to be ligand- and substrate-dependent. In the case of the hydrovinylation of cyclohexa-1,3-diene in the presence of 11, changing the ratio from 1 1 to 1 10 has little effect upon the activity [34], while for PBU3 it is claimed that 1 2 is optimal [25], whereas with PPh3 the best results are obtained with a 1 1 ratio. In this last example, a 1 5 ratio leads to catalyst deactivation [27]. For many of the reactions involving chiral ligands a ratio of 1 1.2 has been chosen, but in the case of the hydrovinylation of cy-cloocta-1,3-diene in the presence of P(menthyl)2Pr the catalyst is still quite active at a 1 3.8 ratio [3, 39]. 

Subsequent dihydroxylation was carried out advantageously under two-phase conditions. No significant self-induction of diastereomer formation was observed by the AD-type ligand-cum-substrate (ratio of 1,2-diols 1.2 1). Subsequent NaI04-mediated diol cleavage afforded the desired acetylated rubanone 74b in 86% isolated yield on a 20 g scale. Given this reliable synthetic route, the door is open to further elaboration such as the Mannich a-aminomethylation of the carbonyl system. Thus, seminatural cinchona alkaloids have become accessible. Selected examples of possible transformations are discussed in the following section. 

Alkyl phenyl ketones are reduced to the (R) alcohols with greater selectivity than the alkyl methyl ketones are reduced to the (5) alcohols. Optical yields vary depending on the chiral ligand (4 being superior to 5) and increase on increasing the [i-PrOH]/[substrate] ratio (the reverse reaction becoming less thermodynamically favored). Formation of catalytically active species from the complex requires displacement of the cyclooctadiene from the coordination sphere of the metal. The enantioselectivity observed is explained in terms of the equilibria between the diastereoisomeric forms of this catalytically active species. 

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