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Heterocyclic Chemistry Volume 5
A Review of the Literature Abstracted Between July 1982 and June 1983
By H. Suschitzky The Royal Society of Chemistry
Copyright © 1986 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-843-1
CHAPTER 1
Three-Membered Ring Systems
BY T.J. MASON
1 Reviews
1.1 General. - The reactivities and conformations of systems in which three-membered heterocycles are conjugated with unsaturated groups have been reviewed.
1.2 Rings Containing Oxygen. - The catalytic epoxidation of alkenes together with the mechanisms of such epoxidations, using organic hydroperoxides and molecular oxygen have been surveyed as have the preparations of acyloxiranes by nucleophilic epoxidation of conjugated enones and the reactions of oxirans with carbonyl compounds.
One of the major recent advances in the synthesis of chiral oxirans has been the introduction of Katsuki Sharpless reagents for which some recent developments have been reported. The importance of chiral oxirans is their function as starting materials for the synthesis of optically pure natural products and drugs.
1.3 Rings Containing Nitrogen. - The synthesis of chiral aziridines and research in the field of aziridine chemistry have been surveyed.
A major review of the generation of nitrile ylides and nitrenes from 2H-azirines has been published as has a review on the thermolysis and photolysis of diazirines.
2 Oxirans
2.1 Preparation
2.1.1 Oxidation of Alkenes Using Oxygen or Oxygen Containing Gases. The patent literature provides formulations for oxidation catalysts consisting of silver doped with Na and K salts supported on α-Al2O3. Silver-gold alloy has also been found to be effective as a catalyst. A study of the mechanism of epoxidations using this type of catalyst has revealed that selectivity for both propene and ethene oxide is low when the gold content is high. The comparatively low selectivity for propane oxide formation by direct oxidation of propene over silver catalysts has been found to be due mainly to the slow formation of the epoxide and not to consecutive oxidation of water and carbon dioxide. The propene reacts initially with O-2 at the catalyst surface to form a stable 'hydrocarbon 'type layer which poisons the catalyst. No such layer could be detected during ethene epoxidation where the mechanism involves the formation of an ethene-atanic oxygen absorption complex, the surface residence time for which depends upon the rate of electron transfer. The surface of such silver catalysts, during the epoxidation reaction, have been analysed using Auger electron emission spectroscopy and by XPS. The selectivity of silver catalysts can be improved by using spherical pellets which are only partially (rather than uniformly) impregnated with catalyst. Catalyst activity can also be significantly raised for the epoxidation of ethene by operating under pulsed rather than stationary conditions.
A mild, regiospecific, epoxidation procedure for dienol acetates catalysed by [Fe3O(OCOCMe3)6(MeOH)3]Cl has been reported. In a typical experiment (1) (300mg) and the catalyst (30mg) were stirred for 20h at 60°C to give (2) (82%) and minor amounts of degradation products.
Photoepoxidation of propene is achieved with high selectivity (90-95%) using a high pressure mercury or a tungsten filament lamp, and biacetyl sensitizer in dischlorobenzene solvent. Pressurisation of the reaction resulted in a significantly increased rate and pennitted the use of greater concentrations of propene and oxygen . An interesting rearrangement occurs in the tetraphenylporphine-sensitized photo-epoxidation of chromenol acetate (3;R=CH3,OCH3). After formation of the initial peroxide (4) migration of the acetate group occurs to give an almost quantitative yield of the unstable epoxides (5) (Scheme 1).
The presence of polyglycols has been found to increase the reaction rate and yield of styrene oxide in the liquid phase oxidation of styrene by oxygen. This result suggests the possible participation of an intermediate polymeric species in the reaction.
The liquid phase oxidation of cyclohexene with oxygen in the presence of soluble vanadium compounds eg. VO(acac)2 and AZBN gives 2,3-epoxycyclohexan-l-ol.
2.1.2 Oxidation of Alkenes Using Peroxy-acids. High yields of n-alkyloxiranes (6;R=(CH2)nCH3, n=4-17) are obtained from the oxidation of the corresponding terminal alkenes using peroxyprop- or peroxybutanoic acids. Thus dec-l-ene was epoxidised by a solution containing EtCO3H, H2O, H2O2 and 10ppm H2SO4 in benzene with 99.6% conversion. The same peroxyacids have also been used in aqueous acetic acid solution to oxidise alkenes dissolved in chlorofonn eg. α-pinene yields epoxide (95%). A study of the kinetics of epoxidation of a number of cyclopent-2-enyl and cyclohex-3-enyl peroxides eg. (7; R=CMe3, CMe2Pr) and (8; R=CMe3), has revealed that the former were the least reactive and that an isokinetic temperature exists at 285±2 K.
An interesting difference in stereoselectivity between epoxidations using peroxyacid and peroxide is revealed in the reaction of (9) with 3-ClC6H4CO3H (MCPBA) and Me3COOH (TBHP). Only the β-epoxide was formed using the former whereas a mixture of both stereoisomers resulted fran epoxid:ation with TBHP. High selectivity is also shown in the reaction of MCPBA with [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] at -20°C leading to almost exclusive formation of β-epoxide (11). The same substrate treated with TBHP in the presence of Ti(OCHMe2)4 at -'20°C generates the α-epoxide. A possible explanation for these results involves the coordination of MCPBA with the hydroxyl and etherial moieties of (10)thus allowing a pseudo-intramolecular epoxidation to occur from one face only. In the case of TBHP the Ti(OCHMe2)4 is thought to coordinate in a similar manner to MCPBA thus blocking one face and permitting TBHP to approach only from the other side.
Direct epoxidation of α-methylstyrene with MCPBA leads to poor yields (<30%) of the epoxide due to side reactions; for this reason this system was chosen to evaluate the epoxidising efficiency of the solid 1:2 complex between MCPBA and KF. The comlex loses activity quickly in the solid form but, when suspended in solvents such as CH2Cl2, it is stable enough to give up to 90% yields of α-methylstyrene oxide.
A preparation of 18O-labelled MCPBA has been described. The method involves oxidation of sodium with 50% enriched 18O2 to give sodium oxide which was treated with 3-ClC6H4COCL in THF to give MCPBA with 39% total active 18O. This could be used to generate epoxides eg. cyclohexene oxide enriched with 18O.
The reaction of MCPBA with medium ring alkenes possessing hydroxymethyl or carboxyl functional groups gives bicyclic ethers or lactones. Thus (12) gives (13) (32%) via participation by the neighbouring hydroxyl group.
2.1.3 Oxidation of Alkenes Using Peroxides. The efficiency of hydrogen peroxide as an epoxidising agent is markedly improved. by the presence of a catalyst. Cyclohexene has been epoxidised in good yield in the presence of molybdic acid-charcoal or WO5.HMPT.H2O catalysts. The influence of the solvent in such reactions is also important;thus in the epoxidation of allyl chloride catalysed by arsenic (4-Methoxyphenylarsonic acid) the conversion was increased from 57.4% in dioxane to 93.2% in propanoic acid. A new class of reactive spirooxirane heterocycles [eg. (14)(76%)] have been prepared by the oxidation of the parent pyrazolinone with H2O2 in methanol containing NaOH.
Hydrogen peroxide may also be used to generate an oxidised intermediate which itself is capable of epoxidising alkenes. One such intermediate is formed from nitriles, thus addition of H2O2 to trichloroacetonitrile gives Cl3CC(:NH)OOH which is a very reactive oxygen-transfer agent. The reagent is generated in the presence of the alkene under neutral conditions in a two-phase (CH2Cl2/H2O solvent system, The reagent exhibits the same reactivity trends as MCPBA thus providing a mild, practical substitute for the peroxyacid. A similar intermediate (peroxybenzimidic acid) is formed when PhCN is treated with H2O2. The experimental conditions require a suspension of alkene, PhCN, and K2CO3 in methanol to which is added the H2O2; using this technique cis and trans-epoxides (3:2 ratio) were formed in 94% yield from (15).
The addition of H2O2 to a CH2Cl2 solution of alkene and [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] followed by stirring at room temperature for up to 24h gave epoxides in 66-100% yields. The intermediate responsible for the epoxidation is an O-alkylperoxycarbonic acid [ROC(O)OOH] formed in situ.
At -80°C the addition of H2O2 to Vilsmeier reagent (Me2N:CHCl)+ PO2Cl2- in the presence of an alkene results in rapid epoxidation (<15 min) via the intermediate (Me2:CHOOH)+PO2Cl2- species. This procedure generated 55-9% epoxides (17; =3->5,9) from the parent alkenes.
Some of the most widely used catalysts for TBHP epoxidation are Mo (VI) compounds which inc1ude naphthenate, abietate and carbide. It has been reported that an oxychloride catalyst (MoO2Cl2) on Amberlite resin is more effective when prepared under aqueous conditions rather than in an organic solvent because of the greater swelling and Mo absorption in aqueous solution. The mechanism for Mo(VI)-catalysed TBHP oxidation of allyl chloride has been investigated. Initial oxidation of the catalyst by TBHP to an active monoperoxo complex is accornpanied by further oxidation to an inactive diperoxo species. Deactivation also results from reaction of the catalyst with Me3COH formed in the epoxidation process. The kinetics of epoxidation of cyclohexene under simultaneous catalysis by Co and Mo compounds have also been studied. The remarkable facility of the Me3Si group for controlling the stereochemistry of epoxidation of allylic alcohols has been demonstrated. Thus when (18; R1=R2=H, R3=nBu) is epoxidised with TBHP using VO(acac)2 catalyst an 85% yield of 22:78 threo:erythro epoxide mixture is obtained. This ratio changed by Me3Si substitution, such that (18; R1=Me3Si, R2=H, R3=nBu) gives a 92:8 mixture favouring threo isomer (19) whereas (18, R1=H, R2=Me3Si, R3=nBu) gives a 1:99 mixture with erythro (20) predominating. Similar results have been reported by other workers.
Molybdenum cornpounds have been found to be efficient catalysts for epoxidations using cumene peroxide; thus Na3PMo12O40 and AlPMo12O40 give 100% selectivity in the epoxidation of hex-l-ene50 The mechanism for this reaction is thought to involve the formation of Mo glycol complexes as the true catalytic species. In the epoxidation of styrene, soluble Mo salts were found to be the most effective catalysts yielding the highest conversions (89-94%) with highest selectivity (71-83%) compared with salts of Co,Mn,Ni,Cr,V,W,Ti,Zr,Rh and T1.
A new reagent for the facile and regioselective epoxidation of alkenes can be generated from superoxide anion and nitrobenzene-sulphonyl chlorides. The reagent (21), generated in situ, is effective in forming the monoepoxides (22) (87%) and (23) (78%) from their respective parent dienes.
2.1.4 Via Halohydrin Cyclisations and Related Reactions. A simple synthesis of vinyl oxiran (26) (70-76%) involves the acidic cleavage of (24; X=Cl,Br) to (25) followed by dehydrohalogenation.
Denitroamination of the α-hydroxynitroamines ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]) with Ac2O and pyridine at room temperature overnight gave the oxirans (28; R=AcO,H) and (29) in 82, 71 and 71% yield respectively. The mechanism involves intramolecular nucleophilic displacement by the hydroxyl group of the intermediate nitrous oxide separated ion pair.
An interesting synthesis of phenyloxiran (31) (85%) is provided by the reaction of (30) with SO2Cl2 in CCl4. This synthesis is remarkable in that the same reaction carried out in benzene follows a different course to yield (32) (88%).
Hindered oxirans may be synthesised from hindered ketones via β-hydroxyselenides. Treating 2,2,6-trimethylcyclohexanone with MeSeCMe2Li in THF at -45°c for 3h gave (33) (77%) which with FSO3Me followed by aq KOH and Et2O at O°C for 1h gave (34) (95%).
The β-dicarbonyl compounds (35; R=CO2Me,CO2CMe3,COMe) formed ketals (36) (50-95%) with HOCH2CH(OH)CH2Cl (Scheme 2). Cleavage of (35) using (CH3)3COK in (CH3)3COH gave the glycidyl enol ethers (36) by displacement of Cl-.
The epoxidation of allylic alcohols can be achieved with a high degree of stereocontrol through cyclic iodo-carbonates. After conversion of an allylic alcohol (37) to iodocarbonate (38) (85%) (cis:trans ratio 7:93) the carbonate is dissolved in methanol and treated with Amberlyst resin (-OH form) at room temperature over 2h to yield epoxy alcohol (39) (91%) with a 7:93 erythro:threo ratio. The reaction is also effective for hornoallylic alcohol conversions via six membered cyclic iodocarbonates, eg. (40)yields (41).
2.1.5 From Aldehydes and Ketones. A number of modifications of the Darzens condensation have been reported. The reaction of [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] with [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] in DMF was catalysed by [Et3N+CH2Ph]Cl- and K2CO3 in a two-phase solid-liquid system to give glycidic esters (42). The reaction of 1-bromoacetone with benzaldehyde in THF containing Sn(OSO2CF3)2 and N-ethylpiperidine at -78°C leads to a 61% yield of the aldol products (43) and (44) as an 81:19 mixture. When treated with KF and a crown ether a 70:30 mixture of cis and trans- (45) is formed.
Condensation of alkyl α-chlorcmethyl sulphones with aldehydes in the presence of Me3COK gave good yields ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]). The reaction between the sulphones and ketones also gave rise to epoxides.
An interesting variation in the stereochemistry of addition of dimethyloxosulphonium methylide to 5-acetylpyrrolidin-2-one is produced by the addition of anhydrous ZnCl2. In the absence of the salt a 78:22 mixture of epoxides (47; α-Me) and (47; β-Me) results, whereas, with added ZnCl2, this ratio changes to 23:77.
High yields of monosubstituted oxirans (≥ 90%) have been obtained by the reaction of RCHO (R=aryl, heterocyclic or alkyl groups) with Me2S+I- in MeCN using solid KOH in a solid-liquid transfer process. Sulphonium salts have also been used for annulation reactions; thus (48; n=1->4) on successive treatment with Et3O+BF4- and KOCMe3 gave (49)(62-67%). Very similar results have been obtained by Garst and coworkers, who have extended their studies of epoxy-annulation to the synthesis of unsaturated systems. Thus treating cyclohexanone lithium enolate with sulphonium salt (50) (Scheme 3) results in conjugate addition to (51) followed by ring closure and the generation of (52) (58%).
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Excerpted from Heterocyclic Chemistry Volume 5 by H. Suschitzky. Copyright © 1986 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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