Epoxides conditions

While immobilised polyamino acids can be recovered from a reaction and re-used in subsequent operations, it has been found that after repeated recycling the quality of the catalyst declines, resulting in increased reaction times and reduced stereoselectivity. The quality of the catalyst declines particularly quickly when it is used in the recently developed biphasic epoxidation conditions (see Sect. 4.1.2). This gradual decay of the polyamino acid catalyst led to the development of a regeneration procedure. 

Since the polyleucine epoxidation conditions are only favourable for highly electron-deficient unsaturated systems (i. e. ketones), use of the Baeyer-Villiger oxidation subsequent to the epoxidation reaction allows access to the optically active epoxyesters. 

The improved Julia-Colonna epoxidation conditions have been successfully employed for poly-(D)-leucine. 

Optically active 2-alkylidene-l,3-dithiane 1,3-dioxides have been prepared as chiral Michael-type acceptors. It was shown that these compounds react under nucleophilic epoxidation conditions to give diastereoselectively the epoxides. Other heteroatom nucleophiles reacted as well <1998JOC7128, 1999PS(153/4)337>. It was further demonstrated that enolates were also effective nucleophiles for the stereoselective addition to 2-alkylidene-l,3-dithiane 1,3-dioxides (Scheme 48) <20050L4013>. 

Other advantages include a mechanism that allows one to rationalize and predict the stereochemical outcome for various olefin systems with a reasonable level of confidence utilising a postulated spiro transition state model. The epoxidation conditions are mild and environmentally friendly with an easy workup whereby, in some cases, the epoxide can be obtained by simple extraction of the reaction mixture with hexane, leaving the ketone catalyst in the aqueous phase. 

When dienones such as 55 are subjected to the epoxidation conditions the electron-poorer C=C double bond is selectively epoxidized. The other C=C bond can be functionalized further, for example, it can be dihydroxylated, as shown in the synthesis of the lactone 56 (Scheme 10.11) [82]. Stannyl epoxides such as 57 (Scheme 10.11, see also Table 10.8, R1 = n-Bu3Sn) can be coupled with several electrophiles [72], reduction of chalcone epoxide 58 and ring opening with alkyl aluminum compounds provides access to, e.g., the diol 59 and to phenylpropionic acids (for example 60). Tertiary epoxy alcohols such as 61 can be obtained with excellent diastereoselectivity by addition of Grignard reagents to epoxy ketones [88, 89]. 

The known allylic alcohol 9 derived from protected dimethyl tartrate is exposed to Sharpless asymmetric epoxidation conditions with (-)-diethyl D-tartrate. The reaction yields exclusively the anti epoxide 10 in 77 % yield. In contrast to the above mentioned epoxidation of the ribose derived allylic alcohol, in this case epoxidation of 9 with MCPBA at 0 °C resulted in a 65 35 mixture of syn/anti diastereomers. The Sharpless epoxidation of primary and secondary allylic alcohols discovered in 1980 is a powerful reagent-controlled reaction.12 The use of titanium(IV) tetraisopropoxide as catalyst, tert-butylhydro-peroxide as oxidant, and an enantiopure dialkyl tartrate as chiral auxiliary accomplishes the epoxidation of allylic alcohols with excellent stereoselectivity. If the reaction is kept absolutely dry, catalytic amounts of the dialkyl tartrate(titanium)(IV) complex are sufficient. 

The substrate scope of this epoxidation was subsequently investigated using a variety of olefins with a catalytic amount of ketone 1 (usually 20-30 mol%). A variety of hms-substituted and trisubstituted olefins have been shown to be effective substrates (Table 10.1),39 and the high ee obtained with hms-7-tetradecene suggests that this epoxidation is quite general for simple trans-olefins (Table 10.1, Entry 5). Various functional groups such as ethers, ketals, esters, and so on are compatible with the epoxidation conditions (Table 10.1). A variety of 2,2-disubstituted vinylsilanes... 

Other electron-poor alkenes generally require nucleophilic epoxidation conditions. These reactions usually proceed via non-concerted pathways (nucleophilic addition followed by epoxide ring closure), and so do not have the advantage of retaining the alkene geometry. Nevertheless, for the trans-epoxide, which is usually the predominant product, several methods exist that afford excellent levels of enantio-selectivity. 

From Iron(III) Tetraarylporphyrins and Alkenes. N-alkyl porphyrins are formed via side reactions of the normal catalytic cycle of cytochromes P-450 with terminal alkenes or alkynes. N-alkylpor-phyrins formed from terminal alkenes (with model iron porphyrin catalysts under epoxidation conditions) usually have a covalent bond between the terminal carbon atom of the alkene and a pyrrole nitrogen. The double bond is oxidized selectively to an alcohol at the internal carbon. Mansuy (23) showed that, in isolated examples, terminal alkenes can form N-alkylated products in which the internal carbon is bound to the nitrogen and the terminal carbon is oxidized to the alcohol. Internal alkenes may also form N-alkyl porphyrins (24, 25). 

Reaction of racemic 1,2-diazocinone 2 with (S)-(—)-iV-(methoxymethyl)proline methyl ester, followed by crystallization from MeCN, gave the diastereomer (R,S,S)-(+)366-S <2004TA537>. The diazocinone 37a was subjected to epoxidation conditions (oxone, acetone, NaHCO() and subsequent deprotection of the Ar-carbobcnzyloxy moieties with Pd/C-H2 to give 38. 

The efficiency of kinetic resolution is even greater when there is a silicon or iodo substituent in the (3 )-position of the C-1 chiral allylic alcohols. The compatibility of silyl substituents with asymmetric epoxidation conditions was first shown by the conversion of (3 )-3-trimethylsilylallyl alcohol into (2/ ,3/ )-3-trimethylsilyloxiranemethanol in 60% yield with >95% and further exploited by the conversion of ( )-3-(triphenylsilyl)-2-[2,3- H2]propenol into (2 ,3/ )-3-triphenylsilyl[2,3- H2]oxirane-methanol in 96% yield and with 94% gg.io7b,i07c. pentyl group at C-1, the k,A for asymmetric... 

Kinetic Resolution of Acyclic Secondary Allylic Silyl Ethers. (/ )- can catalyze kinetic resolution of acyclic secondary allylic silyl ethers (eq 5). When racemic silyl ethers (7a-7e) are submitted to the optimized epoxidation conditions, the recovered starting materials are found to be enriched in the (5)-enantiomers, and the resulting epoxides (8a-8e) are single diastereomers ery-... 

The synthesis of cryptophycin 52 was accomplished by E.D. Moher et al. using the Shi epoxidation as the key step to install the epoxide moiety diastereoselectively. In the previous syntheses of this moiecuie, the epoxide moiety was always introduced in the last step, using common oxidants such as mCPBA or DMD, and with poor diastereoselectivity. Interestingly, the usual alkene precursor was a very poor substrate for the Shi epoxidation, so an earlier intermediate was subjected to the epoxidation conditions in which the pH was very carefully controlled. The desired epoxide was obtained as a 6.5 1 mixture of diastereomers. 

Under more normal epoxidation conditions the equilibrium amount of adsorbed and absorbed oxygen is equivalent to about 9 monolayers, a similar thickness to that detected by electron diffraction after several cycles of oxidation and reduction with CO. An indirect measurement of the slow response of the subsurface oxygen concentration to changes in gas-phase oxygen pressure and its effect on catalyst performance has been carried out by Levchenko et al. A sudden reduction in oxygen partial pressure results in an immediate loss of activity followed by a much slower response with relaxation times in the range 10—100 min. The activation energy for this process was about 126 kJ mol . ... 

One way in which the adsorption of a chlorine atom could affect more than one adsorption site is if the chlorine is incorporated into the subsurface oxide layer. No direct evidence of chloride accumulation in the catalyst subsurface has been published. However, there is at 373 K an apparent competition between chlorine and oxygen for adsorption sites which, we have argued above, correspond to the formation of the first monolayer of the oxide film. In view of this it would be surprising if chloride accumulation in the subsurface did not occur under practical epoxidation conditions. The net result would be to modify the electronic properties of this semi-conducting layer and hence the adsorptive properties of the surface. The chloride catalysed reorganization of surface silver atoms is perhaps indirect evidence of such an affect. ... 

Epoxidation conditions Iminium salt (5 mol%), Oxone (2 equiv), Na2CO3 (4 equiv), MeCN H2O (1 1), 0 "C, 2 h. Enantiomeric excess determined by NMR with Eu(hfc)3 (0.1 mol equiv) as chiral shift reagent or by Chiral HPLC on a Chiracel OD column. 

Epoxidation conditions Iminium salt (10 mol%), TPPP (2 equiv), solvent, —40 "C, 24 h Isolated yield. 

Propylene epoxidation conditions catalyst weight 0.3 g hydroperoxide 5 mmol solvent 100 ml epoxidation time 1 h epoxidation temperature 100 °C propylene pressure 8 bar. 1-Octene epoxidation conditions catalyst weight 0.3 g hydroperoxide 5 mmol 1-octene 100 ml epoxidation time 1 h epoxidation temperature 110 °C. 

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