Heavy fluorous

A somewhat different approach was used by Vincent in phase-switching reactions using pyridyl-labelled substrates and products. The pyridyl-containing tag is here thought of as a masked phase tag, which allows for phase switching with the help of a heavy fluorous copper(ll)-carboxylate complex. Comparison with a non-fluorous system indicated that a problem of release of the strongly coordinating pyridine linker was avoided in the fluorous approach. ... 

According to a loose convention, heavy fluorous (F > 60%) and light fluorous ... 

The most appealing feature of fiuorous chiral catalysts is their easy separation from the reaction products, and possible recycling. To this end, emphasis was initially placed on the FBS approach, which is only effective for heavy fluorous catalysts with high or at least moderate partition coefficients in perfluorocarbons. Besides being synthetically demanding, heavy fiuorous chiral catalysts can exhibit unpre-dictably low activities and stereoselectivities, even after careful optimization of the FBS reaction conditions. These seem to be less-compelling issues for relatively simple hght fiuorous chiral catalysts that can be quickly evaluated under the... 

It might be added that the multiphase operation offers more than the decisive separation between desired products and catalyst, although there are differences between the various multiphase hquids [9]. It cannot be emphasized enough that the use of polar multiphase Hquids also separate the byproduct heavy ends from the catalyst in the system, thus avoiding a build-up in the catalyst recycle. In other processes (and probably also if very apolar fluorous liquids are used) an additional purge is needed to remove the high boilers from the catalyst, which then requires a further (and costly) separation or purification [10],... 

Other heavy terminal olefins behave similarly to 1-decene (Table 2), giving, for example, with phosphite 8, an l/b ratio of about 3.0 and an aldehyde selectivity of 95%, but the activity drops markedly going from 1-decene to 1-dodecene, presumably again due to their partial solubility with the fluorous solvent CgFi H. 

CH2)mRfn and serve a like dissolves like function. When such phase labels are present in sufficient length or quantity, the fluorous phase affinity (fluorophilicity) of the compound can be extremely high. This characteristic is used in the design of dyes that adhere strongly to Teflon. Molecules that have large numbers of such fluorine atoms - typically from 39 to > 100 - are called heavy fluorous compounds. However, for certain applications moderate fluorous phase affinities suffice, and for the compounds used in such applications, the term light fluorous is sometimes utilized (Table 3.1). 

As reflected by the fluorous reactions described in Section 3.3, and quantified by data below, most organic compounds have very low affinities for fluorous phases compared with organic phases. Thus, products can often be separated from heavy fluorous catalysts or spent reagents using a simple liquid/liquid phase separation, as shown in Figure 3.2. If necessary, the fluorous phase can be extracted using additional organic solvent. 

This section describes applications of fluorous compounds in fluorous solvents. Most of the compounds presented contain a large number of fluorine atoms - heavy fluorous molecules - and display a high affinity for fluorous solvents. This property allows the easy separation of the fluorinated material, either by extraction or by filtration, and in many cases its recycling. 

The first wave of research into fluorous compounds focused exclusively on using fluorous solvents as separation media. The first publication on the use of fluorous silica gel in 1997 marked a dividing point,as the field began to diverge into what are now often called its heavy and fluorous branches. 

Heavy and light fluorous molecules and separation strategy... 

In a simple view, both heavy and light fluorous molecules can be divided into an organic domain that controls the reaction chemistry and a fluorous domain that controls the separation chemistry. This view coincides with the principles of strategy level separations, which dictate that reactions should be purified only by simple workup-level procedures whenever possible. In the ideal separation, the target products of a reaction partitions into a phase that is different from all of the other reaction components, thereby allowing rapid and in many cases environment friendly isolation. The fluorous ponytails (permanent domains) or tags (temporary domains) on both heavy and light fluorous molecules allow them to partition into a fluorous phase under suitable workup conditions. 

Heavy fluorous techniques use fluorous reaction components that have a large number of fluorines. Heavy fluorous molecules can have as few as 39 fluorines, but it is not uncommon for them to have >50 or even >100. Such a high fluorine content gives heavy fluorous molecules unusual properties, and they can be separated from reaction mixtures by simple separation techniques such as extraction with a fluorinated solvent or even just filtration (see Section 3.3). However, the unusual properties that facihtate separations can complicate reactions since heavy fluorous molecules sometimes do not behave well under standard reaction conditions, and a search for suitable solvents and reaction conditions is a prerequisite. 

As chemical synthesis moves from discovery to production, scales increase and the use of catalytic rather than stoichiometric quantities of reagents is increasingly advantageous from both the economic and environmental standpoints. The vast majority of fluorous catalysts prepared to date are best classified as heavy fluorous catalysts, and they are removed from the reaction mixture by liquid/liquid separation techniques. On the one hand, fluorous silica gel provides another option for these catalysts, which is to use a solid/liquid separation instead. On the other hand, fluorous silica gel enables the use of light fluorous catalysts, such as the palladium catalyst shown in Scheme 36. Mizoroki-Heck reactions are promoted by standard conductive heating (oil bath) or microwave heating. After cooling and solid-phase extraction. 

Fluorous biphasic and triphasic reactions are at once similar and different. Like fluorous biphasic reactions (see Section 3.3), fluorous triphasic reactions use a fluorous reaction solvent. However, whereas biphasic reactions use heavy fluorous molecules, triphasic reactions use light fluorous molecules or sometimes no fluorous molecules at all. The reaction and separation occur simultaneously in triphasic reactions. Indeed, the reaction drives the separation in most triphasic processes, whereas a separation follows a reaction in biphasic methods. 

Yao and coworkers [ 142] were the first to report a fluorous-functionalized olefin metathesis catalyst. A random, bifunctional, fluorous polyacrylate material, containing both a perfluoroalkyl section and a styrenic Hoveyda ligand section in a 10 1 ratio, was prepared. This was then treated with catalyst 4 to generate the heavy fluorous catalyst 156. This catalyst was then effectively used in a variety of RCM reactions at 50 C, employing a solvent mixture of PhCFj/CHjClj (1 19 v/v). This catalyst system was shown to be efficiently recycled a total of 20 times using a fluorous extraction technique. Unfortunately, no results were reported pertaining to any residual Ru contamination within the organic fractions. 

The concept of fluorous biphase hydroformylation of heavy olefins was introduced by Horvath at Exxon in 1994 [42, 43]. Fluorocarbon-based solvents, especially perfluorinated alkanes and ethers, are of modest cost, chemically inert, and nonpolar and show low intermolecular forces. Most of them are immiscible with water and can be therefore used as the nonaqueous phase. Moreover, their miscibility with organic solvents such as toluene, THF, or alcohols at room temperature is quite low. Only at elevated temperature miscibility occurs. These features allow hydroformylation at smooth reaction conditions at 60-120 °C in a homogeneous system [44]. Upon cooling, phase separation takes place. The catalyst is recovered finally by simple decantation. One of the last summaries in this area was given by Mathison and Cole-Hamilton in 2006 [45]. 

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