Epoxidation electronic effects

The rationalization of stereoselectivity is based on two assumptions. (1) The 1-arylthio-1-nitroalkenes adopt a reactive conformation in which the ally lie hydrogen occupies the inside position, minimizing 1,3-allylic strain. (2) The epoxidation reagent can then either coordinate to the ally lie oxygen (in the case of Li), which results in preferential syn epoxidation or in the absence of appropriate cation capable of strong coordination (in the case of K) steric and electronic effects play a large part, which results in preferential anti epoxidation (Scheme 4.7).52... 

When the epoxide is 1,2-disubstituted, steric and electronic effects are responsible for the preferential formation of one product. In this context, benzyl radicals are always produced irrespective of the substitution pattern of the epoxide. For these intermediates, the more reactive tert-butyl thiol is the hydrogen atom donor of choice. Chelation of titanium can be used to good effect for regioselective epoxide opening, as shown in Scheme 12.8 [5d]. 

The regioselectivity in palladium-catalyzed alkylations has been attributed to the dynamic behavior of trihapto pentadienyl metal complexes60. For example, competing electronic and steric effects influence product formation in dienyl epoxides, but in palladium-catalyzed reactions steric factors were often found to be more important. Thus, alkylation of dienyl epoxide 76 with bulky nucleophiles such as bis(benzenesulfonyl)me-thane in the presence of (Ph3P)4Pd occurred exclusively at the terminal carbon of the dienyl system producing allyl alcohol 77 (equation 39). However, the steric factors could be overcome by electronic effects when one of the terminal vinylic protons was replaced with an electron-withdrawing group. Thus, alkylation of dienyl epoxide 78 affords homoal-lylic alcohol 79 as the major product (equation 40). 

Figure 14.7. Electronic effects in asymmetric epoxidation of cinnamyl alcohols...

SCHEME 67. Steric and electronic effects in the diastereoselective catalytic epoxidation of cyclic olefins and aUyUc alcohols with MTO/UHP... 

Electronic effects can also play a part in determining which face is attacked. In the adamantane derivative 17 steric effects are about the same for each face of the double bond. Yet epoxidation, dibromocarbene attack (5-50), and hydroboration (5-12) all predominantly... 

The postulated hydroperoxide-molybdenum complex indicates that there should be a steric and an electronic effect by the alkyl and aryl groups of the hydroperoxide. The steric effect is important in the transition state. The electronic effect will influence the rate of complex formation and the epoxidation reaction. Some data (Table VII) were obtained for these effects, but a clear distinction or evaluation of their role cannot be made at this time. 

Mechanism. The following types of evidence ere pertinent in selecting on acceptable mechanism for olefin epoxidation by means of peroxy acids (1) the nature of the peroxy acid and the electronic effect of eubBtituents on its reactivity (2) the electronic effect of substituents on the reactivity of the olefin component (3) stereochemical factors affecting the reactivity of the olefin (4) the possibility of acid dialysis (5) solvent effects and (6) neighboring group effects. 

Kureshy et al. have reported that ruthenium-Schiff base complexes 27 serve as a catalyst for enantioselective epoxidation of styrene derivatives (Scheme 6B.26) [71], An electronic effect similar to that described in the Mn-salen-catalyzed epoxidation (vide supra) is observed in this epoxidation, that is, an electron-donating group on the catalyst and electron-withdrawing group on the substrate lead to higher enantioselectivity. For example, the epoxidation of styrene with 27c shows modest enantioselectivity (38% ee), whereas that of m-nitrostyrene with 27a exhibits much higher enantioselectivity (80% ee). 

A study carried out with various K-region arene oxides shows that the reactivity order of epoxides with sodium cresolate in DMSO is 29 > 28 > 1, 253 > 4 > 254. The poor regioselectivity observed in the reactions of 28 and 29 with the cresolate is attributed to the insensitivity of the reaction to electronic influences as well as by the inherent absence of the electronic effects on the condensed benzo ring.24... 

The alkoxycarbonyl group does not have a strong directing effect on the ring opening of epoxides by amines (Scheme 4.76), and steric or electronic effects of the other substituents can be more important to the outcome of these reactions. The... 

Dimethyloxazolidines have been utilized as chiral auxiliaries for the diastere-oselective functionalization of the optically active tiglic acid derivatives by means of epoxidation with dimethyldioxirane (DMD) or m-CPBA and ene reactions with 02 or 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). In the DMD and m-CPBA epoxidations, high diastereoselectivities but opposite senses of diastereomer selection was observed. In contrast, the stereochemistry of the 102 and PTAD ene reactions depended on the size of the attacking enophile whereas essentially perfect diastereoselectivity was obtained with PTAD, much lower stereoselection was observed with 02. The stereochemical results for the DMD and m-CPBA epoxidations and the PTAD ene reaction are explained in terms of the energy differences for the corresponding diastereomeric transition states, dictated by steric and electronic effects.200... 

Several catalysts have been found for the ring opening of epoxides. For instance, cyclohexene oxide gave an excellent yield of the trans-fi-amino alcohol when treated with either aromatic or aliphatic amines in the presence of a scandium triflate catalyst.21 Aromatic epoxides react in a regiospeciflc reaction at the benzylic carbon when treated with aromatic amines and scandium triflate but at the least substituted carbon of the epoxide ring when aliphatic amines react. Electronic effects are more important in the reactions of the aromatic epoxides whereas steric factors control the reaction with aliphatic epoxides. 

During our further studies of ketone catalysts, ketone 16 was found to be highly enantioselective for a number of acyclic and cyclic d.s-olefins (Table 10.6).73-74 It is important to note that the epoxidation is stereospecific with no isomerization observed in the epoxidation of acyclic systems. Ketone 16 also provides encouragingly high ee s for certain terminal olefins, particularly styrenes.74-75 In general, ketones 1 and 16 have complementary substrate scopes. In our subsequent study of the conformational and electronic effects of ketone catalysts on epoxidation, ketone 17, a carbocyclic analog of 16, was found to be highly enantioselective for various styrenes (Table 10.7).76... 

The Pd(0)-catalyzed allylation of 96 with acrolein dimethyl acetal gives exclusively compound 104. The 7j3-allylpalladium cationic complex (4, R = OMe) is attacked only at the center bearing the substituent MeO (80SC147), thus emphasizing the importance not only of steric effects in the electrophile but also of the electronic effects in the Tsuji-Trost reaction (92T1695). Indole 96 has been also allylated with epoxide 105 under Pd(0) catalysis by Trost and Molander (81JA5969). The intermediate cationic complex is attacked at the exocyclic position, 106 being formed, as shown in Scheme 22. 

The stereochemical outcome of this transformation deserves special comment. Based on established mechanistic grounds, the likely intermediate in this process is the transient 1,2-epoxide, 107 (Eq. 15). Reaction with nucleophiles occurs exclusively at C-l as a result of powerful electronic effects, as evidenced by the exclusive formation of 1-azidoad-ducts 104 and 105. However, the resulting stereochemistry of the 1-sub-stituted-2-hydroxy adducts depends greatly on the reaction conditions. For example, Rebek reported that a cis-1 -methoxy-2-hydroxy adduct was isolated as the major product when bromohydrin 106 was exposed to basic reaction conditions (NaOMe/MeOH).80 In this case the product cis/trcms ratio was found to be inversely proportional to the base concentration, a fact suggesting that the minor trans-adduct arose directly via Sn2 attack on the epoxide 107. To explain the formation of the cis-adduct,... 

Figure 10.2 illustrates selected examples of these epoxide products. Aromatic and heteroaromatic aldehydes proved to be excellent substrates, regardless of steric or electronic effects, with the exception of pyridine carboxaldehydes. Yields of aliphatic and a,/ -unsaturated aldehydes were more varied, though the enantio-selectivities were always excellent. The scope of tosylhydrazone salts that could be reacted with benzaldehyde was also tested (Fig. 10.3) [29]. Electron-rich aromatic tosylhydrazones gave epoxides in excellent selectivity and good yield, except for the mesitaldehyde-derived hydrazone. Heteroaromatic, electron-poor aromatic and a,/ -unsaturated-derived hydrazones gave more varied results, and some substrates were not compatible with the catalytic conditions described. The use of stoichiometric amounts of preformed sulfonium salt derived from 4 has been shown to be suitable for a wider range of substrates, including those that are incompatible with the catalytic cycle, and the sulfide can be recovered quantitatively afterwards [31]. Overall, the demonstrated scope of this in situ protocol is wider than that of the alkylation/deprotonation protocol, and the extensive substrate...

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