Pyrrolidine derivatives epoxidation

Chiral pyrrolidine derivatives, proline, and amino acid-derived imidazolidinones mediate the asymmetric epoxidation of ,/i-unsalurated aldehydes. Protected a,a-diphenyl-2-prolinol catalyses the asymmetric formation of 2-epoxyaldehydes, with hydrogen peroxide or sodium percarbonate as the oxygen sources, with 81-95% conversion with up to 96 4 dr and 98% ee.204... 

The palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a [42] and aziridine 20b [39] with the activated olefin 4a for the formation of five membered cyclic ether 21a and pyrrolidine derivative 21b has also been reported in our laboratories. The mechanistic issue is very much similar to that discussed in Scheme 9. Pd(0) catalyst added oxidatively to 20 to produce the 7r-allylpalladium complex 22. The Michael addition of a hetero nucleophile in 22 to the activated olefin 4a gives 23 which undergoes intramolecular nucleophilic attack on the inner 7r-allylic carbon atom to give the cy-clized products 21 and Pd(0) species is generated (Scheme 10). Similarly, the palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a with the N-losylimincs 24 is also known (Scheme 11) [43]. Intermolecular cycloaddition of vinyl epoxides and aziridines with the heterocumulenes such as isocyanates, carbodiimides and isothiocyanates is also known [44,45]. Alper et al. reported the regio- and enatioselective formation of the thiaolidine, oxathiolane, and dithiolane derivatives by the palladium-catalyzed cyclization reaction of 2-vinylthiirane with heterocumulenes [46]. 

Simple amines in the presence of Oxone oxidize alkenes to oxiranes. For example, Oxone, pyridine, and a 2-pyrrolidine derivative in a medium of aqueous acetonitrile selectively converts the triene in Equation (72) to a single epoxide. This process also proceeds using noncyclic alkenes. The mechanism is believed to proceed via a single-electron transfer (SET) process involving radical cation intermediates <2000JA8317>. 

Armstrong a al. found that stoichiometric use of chiral pyrrolidine-derived iminium salt 63 (Figure 13 could only be isolated in impure form) in the asymmetric epoxidation of phenylcyclohexene gave the oxirane with 22% ee < 1999T2341 >. 

A. Armstrong, G. Ahmed, 1. Garnett, K. Goacolou, Pyrrolidine-Derived iminium salts as catalysts for alkene epoxidation by Oxone , Synlett (1997) 1075. 

Radicaloid insertions of olefins into the Rh H bond of [Rh (TPP)(H)] has been used to obtain Rh —CH2—(alkyl)—Nu// species (NuH = OH, NH) using olefins functionalized with end-on —OH and —NH functionalities. Under basic conditions, intramolecular SN2-type attack of the Nu at the a-carbon atom of Rh —CH2—(alkyl)—Nu yields [Rh (TPP)] and cyclic organic products (—CH2—(alkyl)—Nu—) (see Fig. 47). Protonation of [Rh TPP)] then allows regeneration of [Rh° (TPP)(H)]. The combination of these reactions constitutes a new method for selective intramolecular anti-Markovnikov hydrofunctionalization of olefins with O—H and N—H functionalities (150). In this way, three-and five-membered ring compounds (epoxides, furan derivatives, pyrrolidine derivatives) were readily obtained. Formation of four- or six-membered rings... 

Compound 79 was also converted to the epoxide 83 in two steps, which upon hydrogenation followed by treatment with di-ferr-butyl dicarbonate afforded the pyrrolidine derivative... 

A computational study of the two possible mechanisms for the asymmetric epoxidation of conjugated aldehydes with H2O2, catalysed by chiral pyrrolidine derivatives lacking proton donor groups, indicates that the more probable route is via formation of an iminium intermediate rather than the general base-catalysed mechanism. The oxidant H2O2 acts as a co-catalyst in the initial formation of the iminium species. The epoxide... 

There is continued interest in chiral syntheses of pyrrolidines, piperidines, and related bicyclic systems. A review has appeared, in Russian, on the stereoselective synthesis of proline and pipecolic acid derivatives from sugars. The antifungal pyrrolidine (+)-preussin (74) has been made from the glucose-derived epoxide (73) as indicated in Scheme 16,58 whilst... 

Astonishingly enough, enantioenriched lithiated cyclooctene oxides 142, originating from (—)-sparteine-mediated lithiation of 124 by i-BuLi/(—)-sparteine (11), could be trapped by external electrophiles, resulting in substituted epoxides 143 (equation 31) ° . Again, the use of i-PrLi furnished better enantioselectivities (approx. 90 10). Lithiated epoxides, derived from tetrahydrofurans and A-Boc-pyrrolidines, undergo an interesting elimination reaction . ... 

The lithium derivative of the chiral chelating diamine (3 )-2-(l-pyrrolidinylmethyl)-pyrrolidine (6) has been used extensively in stereoselective synthesis, i.e. in the deprotonation of ketones and rearrangement of epoxides to homoallylic alcohols. The lithium amide has been crystallized from toluene solution, and X-ray analysis revealed that it forms a ladder-type tetramer with the two pyrrolidine nitrogens solvating the two lithiums at the end of the ladder38, (Li-6)4. 

The heterocyclic hemi-aminal 44 was formed as a model for the synthesis of the marine alkaloids zoanthamine and zoanthenol and is derived from the cyclic imine formed by the reduction of an appropriated substituted azide <07H(72)213>. A pyrrolidine-fused azepine has been isolated from the venom of the ant Myrmicaria melanogaster and assigned as 45 based upon GC and FT-IR comparison with synthetic material <07JNP160>. The axially chiral doubly bridged biphenyl azepine 46 has been synthesised and used with oxone as an epoxidation catalyst in a biphasic system <070BC501>. 

Yang and co-workers have suggested that the inherent difficulties in the preparation/isolation of unstable exocyclic iminium salts can be overcome by in situ formation of the catalytic species from chiral pyrrolidines and aldehydes. The catalytic asymmetric epoxidation of phenylcyclohexene and dihydronaphthalene mediated by the iminium salt derived from pyrrolidine 67 and aldehyde 68 has been examined (Scheme 27) <20010L2587>. 

Depazay and co-workers have described the synthesis of a series of polyhydroxylated pyrrolidine, piperidine and azepanes derived from D-mannitol as novel mimetics of somatostatin [8]. The synthesis of one piperidine 116 is shown in O Scheme 9. The authors used reaction of tr) tamine with the D-mannitol derived bis-epoxide 112 followed by protection of the indole nitrogen with a Boc group to prepare the L-gulo-piperidine 113, the azepane 114 also being formed. Selective protection of the primary alcohol followed by reaction with hydrazoic acid... 

Epoxidations. A mixture of Oxone and an iminium salt derived from pyrrolidine is an effective epoxidizing agent. An imino group can also be exploited for directing epoxidation of a proximal double bond.- The oxodiazepinium salt I- and 4-oxothiane-S,S-dioxide are also general and efficient catalysts. A popular approach to asymmetric epoxidation of alkenes is based on generating dioxiranes in situ from chiral ketones and Oxone . ... 

The 1,3-dipole species arising from electronically activated cyclopropanes and a Lewis acid can be trapped by allylsilanes [505, 506]. Epoxides [507] and aziridines [508] also serve as 1,3-dipole precursors to react with allylsilanes inter- or intramolecularly, affording 2-silylmefhyl-THF derivatives and pyrrolidines, respectively (Scheme 10.189). 

Epoxidations. Combination of Oxone and the iminium salt derived from pyrrolidine and o-trlfluoromethylbenzaldehyde is effective for epoxidation of alkenes. In the case of an active alkene (e.g., trisubstituted alkene), pyrrolidine is an adequate catalyst. Other types of mediators include a-functionalized ketones (e.g., ot-acetaminoacetone) and the A, A -dialkylalloxans 1. ... 

Functionalized organolithiums that an a-oxidoalkyllithium derived from epoxides, ether, and a masked hydroxymethyl pyrrolidine. Acetals of tricarbonylchromiu... 

Functionalized organolithiums that are prepared by the cleavage protocol include a-oxidoalkyllithium derived from epoxides, ethoxymethyllithium from chloromethyl ethyl ether, and a masked hydroxymethyllithium from A -(chloromethyloxycarbonyl)-pyrrolidine. Acetals of tricarbonylchromium-complexed benzaldehydes undergo reductive cleavage. ... 

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