Chemoselective reactions epoxidation

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. 

The first reports of a reaction of an amine with an aldehyde by Schiff [584] led to the establishment of a large class of ligands called Schiff bases. Among the most important of the Schiff bases are the tetradentate salen ligands (N,N -bis(salicy-laldehydo)ethylenediamine), which were studied extensively by Kochi and coworkers, who observed their high potential in chemoselective catalytic epoxidation reactions [585]. The best known method to epoxidize unfunctionalized olefins enantioselectively is the Jacobsen-Katsuki epoxidation reported independently by these researchers in 1990 [220,221]. In this method [515,586-589], optically active Mn salen) compounds are used as catalysts, with usually PhlO or NaOCl as the terminal oxygen sources, and with a O=Mn (salen) species as the active [590,591] oxidant [586-594]. Despite the undisputed synthetic value of this method, the mechanism by which the reaction occurs is still the subject of considerable research [514,586,591]. The subject has been covered in a recent extensive review [595], which also discusses the less-studied Cr (salen) complexes, which can display different, and thus useful selectivity [596]. Computational and H NMR studies have related observed epoxide enantioselectivities... 

Baeyer-Villiger oxidation (p. 853) catalytic hydrogenation (p. 844) chemoselective reaction (p. 848) dissolving-metal reduction (p. 846) enantioselective reaction (p. 857) epoxidation (p. 855) functional group interconversion (p. glycol (p. 858)... 

The titanium-catalysed reaction is highly chemoselective for epoxidation of allylic alcohols. Thus, the dienol 47 gave only the epoxide 48 (5.58). The reaction is also tolerant of many different functional groups, including esters, enones, acetals, epoxides, etc. 

An acid catalysis leads to protonation of the basic O atom of epoxide and favors the 5-exo-tet approach of the OH group with formation of TM 7.12. On the contrary, a specific antibody developed as a biocatalyst directs the recyclization of 3 by the disfavored 6-endo-tet route and exclusive formation of TM 7.11. This outcome is explained by the preferred conformation of 3 in the active site of the antibody, which closely resembles those on the 6-endo-tet route. Calculations revealed the energy of the transition state for the 5-exo-tet route to TM 7.12 1.8 kcal/mol is lower than for the 6-endo-tet route to TM 7.11. Selective lowering of the TS energy on the route to TM 7.11 is the result of preorientation of bound substrate 3 in the active site of the antibody, an important aspect of the mechanism of many enzymatic reactions. Remember that a less than 3 kcal/mol difference in the transition-state energy on the routes to enantiomeric products assures nearly 100 % e.e. (Sect. 3.4). Similarly, a small energy difference in activation energies determines the direction of chemoselective reactions. 

Epoxides are regio- and stereoselectively transformed into fluorohydrins by silicon tetrafluoride m the presence of a Lewis base, such as diisopropyleth-ylamme and, m certain instances, water or tetrabutylammonium fluoride The reactions proceed under very mild conditions (0 to 20 C in 1,2-diohloroethane or diethyl ether) and are highly chemoselective alkenes, ethers, long-chain internal oxiranes, and carbon-silicon bonds remain intact The stereochemical outcome of the epoxide ring opening with silicon tetrafluoride depends on an additive used, without addition of water or a quaternary ammonium fluoride, as fluorohydrins are formed, whereas m the presence of these additives, only anti opening leading to trans isomers is observed [17, 18] (Table 2)... 

It is interesting to note the chemoselectivity of the reaction double and triple bonds, thioketals, epoxides, nitro and sulfone groups and usual functions are not affected. 

The process is assumed to take place by a chemoselective attack of the dianion 2-223 at the bromomethyl group of 2-221 and subsequent nucleophilic attack of the resultant monoanion 2-224 onto the epoxide moiety to give 2-225. Use of the sodium-lithium-salt 2-223 of the dicarbonyl compound 2-220, the reaction temperature as well as the Lewis acid LiC104, are crucial. The reaction seems to be quite general, since various 1,3-dicarbonyl compounds can be converted into the corresponding furans. 

Alkylation of organomanganese reagents with alkyl bromides can also be improved by addition of CuCI (3 mol%). The reactions proceed at room temperature and are complete within a few hours [123, 130], The opening of epoxides is also improved under these conditions. The reaction also features good chemoselectivity, tolerating the presence of sensitive functions such as ketones (Scheme 2.59) [130]. 

Our preliminary experiments have provided the first example of Lewis acid promoted C-C bond heterolysis of epoxides and productive cycloaddition (eq 7). Under the influence of TiCl4-(THF)2 (2 equiv), epoxide 26 reacts with methyl pyruvate to provide acetal 27 (52% isolated yield), along with C-O cleavage product 28 (23 °C, 3 h). The diaste-reoselectivity for formation of 27 is 2.3 1. We have performed the analogous reaction in the absence of a Lewis acid the thermal reaction requires several days at 110 °C and gives a diastereomer ratio (dr) of ca. 1.3 1... Although not optimized from the standpoint of chemoselectivity, these results are promising because of the relatively low reaction temperature and potential for enhanced diastereocontrol. 

In 2002, Ichihara and coworkers reported on the utilization of a Keggin-type phos-phomolybdate (NH4)3PMoi2O40 on apatite as catalyst for the solvent-free epoxidation of olefins (see Section III.A.3.c) and the oxidation of sulfldes and sulfoxides in the presence of urea hydrogen peroxide (Scheme 104) . Chemoselectivities of the oxidation of the sulfides were good [product ratios (sulflde/sulfoxide) 84/16 up to 91/9] depending on the substrate, temperature and reaction time. 

---