Choice of Precatalysts

Chirotech has invested much time and effort in the development of rhodium Du-PHOS precatalysts. Robust synthetic routes have been developed for these materials, such that commercial quantities of the (DuPHOS Rh-COD) precatalysts are available [11]. In addition, Chirotech has manufactured and supplied [(R,R)-Me-DuPHOS Rh-COD]BF4 1 on a multi-kilogram scale, using the route to the ligand outlined in Fig. 7 [12]. 

It was found that experimental conditions such as rate of stirring have a much more dramatic effect than the choice of precatalyst. For example, hydrogenation of the candoxatril precursor 11 was 4.5 times slower with less efficient stirring (Fig. 8), using either the COD or NBD precatalysts. For this class of reaction, hydrogen mass transfer into solution [15] is the most important single process parameter affecting the overall reaction rate. 

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The activity of catalytic systems based on imidazolylidene carbenes depends on many factors, among which the most important are likely to be the electronic effects of the ligand and the parameters of complexation. Therefore, the dependence of the performance of such systems on, e.g., the choice of precatalyst is not well understood, as in the following example (Equation (34)) in which two similar ligands behave in exactly the opposite way in the systems based on the presynthesized complex or in situ generation of the catalyst 454... 

Both 1,1- and 1,2-disubstituted allenes participate well. If both substituents bear allylic hydrogen, the issue becomes regioselectivity of (3-hydrogen elimination. An obvious solution is to activate one of the possible (3-Hs by proper choice of the substituent. A carbonyl group serves that role, as illustrated in Equations 1.65 and 1.66 [58]. In these cases, the tris-acetonitrile precatalyst was employed, which does not require the addition of an alkyne as a cocatalyst. Interestingly, competing the reaction of a propargyl alcohol with that of an allene as in the case of allenyne 58 (Equation 1.67) showed complete chemoselectivity for reaction of the allene. 

The use of the well-defined PEPPSI-IPr precatalyst led to a significant improvement with respect to the rate and the substrate scope of the Negishi alkyl-alkyl coupling reactions (Scheme 3.62). This precatalyst can also be used to promote the cross-couphng of alkyl or aryl halides and sulfonates with arylzinc chloride reagents at room temperature by judicious choice of the solvent and additive (LiCl or LiBr) [236]. 

By the choice of the enyne substrates, the obtained cyclized products might contain functionalities other than dienes. The unusual catalyst combination of a Pd precatalyst and formic acid enables sequential catalysis initiated by cycloisomerization in a very peculiar way. Kressierer and Muller [16] demonstrated in several cases that the palladium(0)-catalyzed Alder-ene reaction of a-alkynyl M-allyl alcohols 7 furnishes cyclic y,5-enals 8 as a consequence of the in situ enol-aldehyde tautomerism (Scheme 12.2). 

Hydroformylation reactions can be carried out with a variety of precatalysts and also with or without a spectator ligand such as PPhj. The choice of ligand has a significant influence on the regioselectivity of a hydroformylation reaction. Many studies have been made to correlate steric, electronic, and other structural properties of both monodentate and bidentate phosphines with their overall catalytic performances. 

A number of reaction variables or parameters have been examined. Catalyst solutions should not be prepared and stored since the resting catalyst is not stable to long term storage. However, the catalyst solution must be aged prior to the addition of allylic alcohol or TBHP. Diethyl tartrate and diisopropyl tartrate are the ligands of choice for most allylic alcohols. TBHP and cumene hydroperoxide are the most commonly used terminal oxidant and are both extremely effective. Methylene chloride is the solvent of choice and Ti(i-OPr)4 is the titanium precatalyst of choice. Titanium (IV) t-butoxide is recommended for those reactions in which the product epoxide is particularly sensitive to ring opening from alkoxide nucleophiles. ... 

Titanium tetrachloride was the logical choice as the raw material for early Ziegler-Natta catalysts. TiCl is a clear, colorless, hygroscopic liquid that fumes upon exposure to ambient air. TiCl (aka "tickle 4") was (and still is) manufactured in enormous volumes as a precursor to titanium dioxide used as a pigment for paint. Consequently, TiCl was readily available and relatively inexpensive. Also, TiCl had been shown by Ziegler and coworkers to produce some of the most active polyethylene catalysts. Though sometimes called a catalyst, it is more accurate to call TiCl a "precatalyst," since it must be reduced and combined with a cocatalyst to become active. 

Dicobalt octacarbonyl remains a simple and convienent choice for the PKR. The best source and handling of the cobalt catalyst appears to vary, depending on the substrate and the presence of additives. Verdaguer reported no difference in the reaction rate of commercial grade Co2(CO)g versus catalyst purified by sublimation. Other precatalyst, such as tetracobalt... 

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