Chemoselectivity examples illustrating

In a bifunctional compound, if a reagent reacts with one functional group preferentially, even though the other is apparently susceptible to the reaction conditions, the reaction is said to be chemoselective. Two illustrative examples are the reduction of a carbonyl group in the presence of a cyano, nitro or alkoxycarbonyl group (Section 5.4.1, p. 519 see also Metal hydrides, Section 4.2.49, p. 445) and the acylation of an aromatic amino group in the presence of a phenolic group (Section 6.9.3, p. 984). 

Direct conversion of alcohols to phenylselenides is also possible. For example, treatment of 13 with Bu3P/PhSeCN affords the selenide 14 in 82% yield. Irradiation with a sun lamp in the presence of PhjSnH gives the monocyclic dichloride 15 [Eq. (2)] [7]. This example illustrates also the high chemoselectivity for the homolysis of the carbon-selenium bond relative to the carbon-chlorine bond of a gem-dichloride. 

In an application of (Z)-selective alkene formation to enolizable aldehydes, it was noted that the combination of LiCl and DBU was effective for deprotonation by lithium complexation of the Still phosphonate. In this example, the cyclopropyl aldehyde (176) reacted chemoselectively in the presence of the ketone (equation 43). In addition, the ( )-alkene could be synthesized by lithium coordination with a standard HWE methyl phosphonate. As this example illustrates, the trifluoroethyl phosphonate can fill an important void by providing trisubstituted alkenes with sensitive substrates in go< selectivity. From the examples of Marshall and Oppolzer it appears that the application of the reaction to higher order trisubstituted alkenes is selective for the (Z)-isomer. The magnitude of the selectivity is substrate specific and dependent on the rapid rate of eo firo-a-oxyphosphonate decomposition. 

A wide range of other reactions have been exploited in the final cyclisation ( pairing ) step in addition to the examples illustrated here, lactamisa-tions, metal-catalysed cyclisations and cycloadditions have, for example, been exploited to yield final product scaffolds. At its most powerful, the build-couple-pair strategy can allow the combinatorial variation of the scaffolds of small molecules. However, a significant challenge will be to identify reactions other than olefin metathesis that have the broad scope and chemoselectivity needed to yield scores of different ring systems. It is certainly possible that the overall approach may, in the future, be used to prepare small molecule libraries based on hundreds, or even thousands, of distinct molecular scaffolds. 

These examples illustrate the interest of the method, very short times, high yields, and excellent selectivity, since non-conjugated olefins or keto groups remain intact. Unactivated zinc can be used. Instead of temperatures of ca. 180 C, much milder conditions can be used (r.t. to 50 C). The reductions can be run in a bath for quantities less than 1 g larger amounts require the use of a pulsed probe emitter.Olefins activated by acid, ester, dienone, and quinone groups are reduced quantitatively in a few hours, and in many instances, in only minutes. Non-conjugated double bonds remain intact. Examples of this chemoselectivity applied to ene-diones are shown in Fig. 15. 

The following examples illustrate the chemoselectivity of the dimethyltitanocene-mediated methylenation (Scheme 4.26). As for the Tebbe reagent 3, the rate of... 

Many other examples ia the Hterature illustrate the possibiUties of chemoselective hydroborations (124,186—189). For example, selectivity between double and triple bonds has been shown (124). 

Glycopeptides contain many functional groups of different reactivity as well as O- and /V-glycosidic bonds. Therefore, the compatibility and chemoselectivity of the applied reactions is a fundamental prerequisite in glycopeptide synthesis. In this chapter, efficient and generally applicable methods and their combinations will be illustrated by examples [5,8,91. 

The relative reactivity of the alcohol and amine in the example just given could be overturned by conducting a reaction under thermodynamic control. In kinetically controlled reactions, the idea that you can conduct chemoselective reactions on the more reactive of a pair of functional groups— carbonyl-based ones, for example—is straightforward. But what if you want to react the less reactive of the pair There are two commonly used solutions. The first is illustrated by a compound needed by chemists at Cambridge to study an epoxidation reaction. They were able to make the following diol, but wanted to acetylate only the more hindered secondary hydroxyl group. 

An illustrative example of a change in chemoselectivity is the inversion of substrate specificity of the serine protease Subtilisin Carlsberg in the transesterification reaction of ethyl esters of A-acetyl-L-serine and A-acetyl-L-phenylalanine with 1-propanol, measured in twenty anhydrous organic solvents. The enzyme-catalysed reaction with the serine substrate is strongly favoured in dichloromethane, while the reaction with the phenylalanine substrate is preferred in t-butylamine, with a 68-fold change in substrate specificity [313]. 

The utility of reductive amination with NaBHsCN in synthesis is contained in reviews and successful applications have been compiled through 1978. Table 7 provides a variety of examples taken from more recent accounts and chosen to illustrate the versatility and compatibility of the process with diverse structural types and chemoselectivity demands. Thus, esters (entries 2-4, 8-12), amides (entries 3, 6-9, 12), nitro groups (entry 13), alkenes (entry 2), cyclopropyl groups (entry 2), organometallics (entry 5), amine oxides (entry 14) and various heterocyclic rings (entries 1, 3, 5-10) all survive intact. Entry 6 illustrates that deuterium can be conveniently inserted via the readily available NaBDjCN, and entry 15 demonstrates that double reductive amination with diones can be utilized to afford cyclic amines. 

Many other examples of chemoselective enone reduction in the presence of other reducible functionalities have been reported. For instance, the C—S bonds of many sulfides and thioketals are readily cleaved by dissolving metals. " Yet, there are examples of conjugate reduction of enones in the presence of a thioalkyl ether group." " Selective enone reduction in the presence of a reducible nitrile group was illustrated with another steroidal enone. While carboxylic acids, because of salt formation, are not reduced by dissolving metals, esters" and amides are easily reduced to saturated alcohols and aldehydes or alcohols, respectively. However, metal-ammonia reduction of enones is faster than that of either esters or amides. This allows selective enone reduction in the presence of esters"" and amides - -" using short reaction times and limited amounts of lithium in ammonia. 

By controlling reaction conditions and by proper choice of the peroxy acid, it is often possible to favor the Baeyer-Villiger reaction over epoxidation. An illustrative example of the usefulness of the Baeyer-Villiger reaction is the stereospecific, and regio- and chemoselective conversion of the unsaturated bicyclic ketone shown below to a cyclopentene containing three consecutive stereogenic centers. 

The example below illustrates that the Negishi reaction for thiophenes can also be chemoselective. In the case of 5-bromo-5 -iodobithiophene (71), thienylzinc reacted at the iodo position in the presence of Pd(dppf)Cl2 to deliver terthiophene 72 in 77% yield [62],... 

An example of this strategy is illustrated in Scheme 3, which describes the synthesis of a positional isomer of sialyl Lewis. Eor instance, armed glycosyl donor phenyl 2-thio-a-sialoside 11 was chemoselectively activated with NlS/TfOH in the... 

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