Saturated oxygen heterocycles CHRISTOPHER J. BURNS Pfirer Central Research, Sandwich, Kent CT13 9NJ, UK Reviewing the literature published between 1 April 1993 and 30 September 1994 1 2 3 4 4. I 4.2 5 5.1 5.2 6 Introduction Expoxides Oxetanes Five-membered rings Tetrahydrofurans Di hy d rof ur ans Six-membered rings Tetrahydropyrans Dihydropyrans References 1 Introduction This review covers the literature on small ring, i.e. 3+6 membered, ethers only. The literature on medium-ring ethers has recently been covered elsewhere in the journal (M. Elliott, Contemporary Organic Synthesis, 1994, 457j, and a separate review of oxygen heterocycles accommodating additional heteroatoms will be published in a future issue of COS. 2 Epoxides Studies of enantioselective epoxidations of unfunctionalized olefins continues to be an extremely active area of research. Jacobsen and his research group have shown that trisubstituted olefins such as 1 can be epoxidized in high yield and with excellent enantioselectivity using commercial bleach, the manganese complex 2, and catalytic 4-phenylpyridine N-oxide.' Under essentially identical conditions, the cis double bond of conjugated cis,truns-dienes (such as 3) is epoxidized with high regioselectivity, giving the trans-epoxide 4 in good yield and enantioselectivity.' Interestingly, simple trans-epoxides can be obtained in high optical purity from cis-olefins by addition of the quinine-derived salt 6 to the epoxidation reaction. For example, epoxidation of cis-[,'-methyl styrene ( 5 j under these conditions furnished predominantly the trans-epoxide 7.3 Katsuki and co-workers have also examined the use of manganese salen complexes in the epoxidations of alkene~.~ For example, the manganese complex 9 catalyses the epoxidation of But 6 : ' f : b B u l Ph Bu' Bu' 2 NaOCI, PhCsHaNO, CH2CI2 * Ph Ph Ph 1 97% 92% 8.8.3 81%- 4 (87%e.e.) Ph Me * P h y ? M e 0 NaOCI, PhCl Ld 5 7 (81%e.e.) L N + 4 6 the chromene derivative 8 with iodosylbenzene, giving the epoxide 10 in good yield and in high optical purity.s By analysis of the results obtained for the epoxidation of a range of cis-olefins using numerous manganese complexes, Katsuki et al. suggest that cis-olefins approach the manganese 0x0 intermediate 11 along the axis depicted in Figure 1." The use of N-methyl imidazole in conjunction with a manganese complex such as 2 or 9, allows for the use of hydrogen peroxide' or molecular oxygen" as oxidants.Dhal and co-workers have reported the use of a related polymer bound manganese salen complex 13 for the epoxidations of alkenes." Use of this catalyst and iodosylbenzene as oxidant generates the epoxide 14 from indene 12 in 5 1 % yield. There have been a number of publications over the review period concerning the asymmetric synthesis of epoxides by biotransformation; a review containing 64 references has also been published. lo Hager, Jacobsen, and co-workers have shown that Burns: Saturated oxygen heterocycles 189AcHN 02Nm a PhIO, MeCN 78% 9 1 AcHN 02Nyy)J 10 (96% e.e.) R' 11 Figure 1 12 0 13 PhIO, MeCN. r.t. 51% 14 chloroperoxidase (CPO) effectively catalyses the epoxidation of aliphatic cis-olefins, as in the formation of the cis-epoxide 16 from 2-cis-heptene 15.' Veschambre and his research group have examined a range of microbial techniques for the stereospecific reduction of halo ketones, which on treatment with base give optically pure epoxides;12 *- CPO, H202 acetone 78% \.pH5 citrate buffer 0 16 (96%e.e.) 15 -w (i) Montierella isabellina (ii) NaH, benzene 60% 0 17 18 (e.e. > 98%) this procedure is illustrated for the synthesis of cis- 2,3-epoxyoctane 18 from the bromohydrin 17." The differentially protected epoxy diester 21 has been prepared by Crout and his colleagues also employing an enzymatic appr0a~h.I~ Thus, selective hydrolysis of the tartrate derived diester 19 with a-chymotrypsin, followed by some functional group manipulation first afforded the silyl protected chiral diester 20 which on treatment with fluoride anion then generated the enantiomerically pure epoxide 21.Koch, Reymond, and Lerner have raised catalytic antibodies to the hapten 22, and have shown that one of these efficiently catalyses the epoxidation of alkenes such as 23 with hydrogen peroxide/acetonitrile as oxidant. I s The epoxide formed has greater than 98% e.e. OH OTBDMS 19 20 1 BU~NF Et02C A C0,Bu' 21 (e.e. 2 98%) link CONH 0 22 0 23 Other new methods for the synthesis of chiral epoxides include the conversion of chiral trichloromethyl carbinols into terminal epoxides. l 6 Thus, reduction of the trichloromethyl ketone 24 with catecholborane in the presence of oxazaborolidine 25 first leads to the chiral carbinol 26 which, after bis-dechlorination with in situ generated tributyltin hydride, is subjected to base- induced ring closure producing the chiral epoxide 27 in high enantioselectivity.Chan et al. have demonstrated that alkenylsilanols 28 can be epoxidized enantioselectively using the Sharpless procedure, and after protodesilylation terminal epoxides 29 of high optical purity are obtained." 0 OH 24 catecholborane $:h Bun 25 26 (i) Bu,SnCI, NaCNBH3 AIBN, EtOH, A l(ii) Na%&.O 27 (96% e.e.) 190 Contempora y OGanic Synthesis29 (8595% e.e.) Agganval and his co-workers have shown that predominantly trans-epoxides can be obtained from the reaction of aldehydes and sulfur ylides generated by decomposition of a diazo compound in the presence of a sulfide;'" the starting sulfide is regenerated and the process operates as a catalytic cycle.The mechanism shown in Scheme 1 presumably operates, and use of a chiral sulfide such as 32 leads to moderate asymmetric induction. Aggarwal and his group have also shown that the reaction between aldehydes and chiral sulfur ylides (obtained from the treatment of diastereomeric sulfonium salts such as 33 with strong base) also lead to chiral epoxides, though again the e.e.'s are moderate.'" Yamamoto and his group have shown that decomposition of diazoalkanes in the presence of an aldehyde by the bulky aluminium catalyst ATPH (35) is an efficient route to epoxides, as exemplified by the transformation of 34 into 36." 0 R' g s + p' R3 31 Scheme 1 32 33 U C H O \ 34 36 Considerable work continues to be published on novel uses of dioxiranes as epoxidizing reagents.Thus, reaction of the chromanones 37 with dimethyl dioxirane affords the interesting spiro-epoxides 38 in moderate yield,*' while epoxidation of chalcones proceeds in excellent yield.22 Very interesting results have been obtained with the epoxidations of benzofuran derivatives 39, which lead to an equilibrium mixture of the epoxide 40 and quinone methide 41,23 which in turn can be transformed into other products, such as the benzopyran 42 by Diels- Alder reaction with ethyl vinyl ether.'4 The unstable benzoxetes 43 can also be obtained from the mixture of 40 and 41 though on warming, or over time, this reverts to the starting mixture of epoxide and quinone methide." o&pR 0 O H 37 WR 0 o o H 38 39 41 43 42 The diastereoselectivity of dioxirane epoxidations has been examined in a number of different substrates.Adam and his research group have demonstrated that epoxidations of certain allylic alcohols with dimethyl dioxirane lead preferentially to the anti-product, as in the epoxidation of 44 to give the epoxides 45 and 46.*" Substantial quantities of enone, resulting from oxidation of the alcohol moiety, can also be formed particularly if the reaction is performed at higher temperatures. Kurihara et al. have improved the diastereoselectivity in the epoxidation of the cyclohexenol 47 by using a more bulky dioxirane than dimethyl dioxirane (such as 50), or alternatively by protecting the hydroxyl with a silyl ether.27 Armstrong and co-workers have shown that the dimethyl dioxirane epoxidation of the cyclohexene ketone 51 leads to a 1 : l mixture of the syn-epoxide 52 and the diol 53 (presumably arising from facile ring-opening of the anti-epoxide), while in contrast mCPBA gives only the syn-epoxide 52.2" An oxygen labelling experiment indicates that in the latter case the diastereoselectivity arises through ketone-assisted delivery of the peracid, rather than in situ dioxirane formation from the ketone moiety.Bums: Saturated oxygen heterocycles 19144 ><%, acetone 0:: b + 45 46 >95 : 5 47 48 49 51 52 53 Albeck and Persky have devised an efficient route to peptide allylamines 54, and have shown that epoxidation with mCPBA leads to predominantly the threo-diastereoisomer Similar results have been obtained by Romeo and Rich who have also shown that the minor eiythro-diastereomer undergoes preferential decomposition under the acidic epoxidation conditions, thereby enhancing the diastereomeric excess.3o 55 The erythro-epoxides can be synthesized via an alternative route starting from halo ketones 56.3' Thus, reduction with sodium borohydride first affords the erythro halohydrin 57, which on treatment with base gives the desired epoxide 58.Similar compounds have been prepared by Barluenga and his colleagues, again using a ring- closure of preformed hal~hydrins.~~ A related procedure has also been used for the diastereoselective synthesis of disubstituted epichlorohydrins involving the conversion of the ketone 59, via the lithium alkoxide 60, into the epoxide 61.33 NaOMe, MeOH 6888% overall J R CbzN "lul, 58 L 59 60 120°C Me.0 ,Ph H %I 61 An intermediate lithium alkoxide also features in the synthesis of oxiranyl pyridines reported by Florio and T r ~ i s i . ~ ~ In this procedure the 2-chloromethylpyridine 62 is lithiated and reacted with a ketone, such as cyclohexanone, and the intermediate alkoxide formed them undergoes cyclization to give the desired epoxide, as illustrated for the synthesis of the spiro-epoxide 64. A related route to vinyl epoxides 66, involving the addition of the allyl zinc reagent derived from allyl chloride 65 to ketones, has also been reported.35 62 (ii) 64 OH (i) LDA,ZnClz THF, -78°C @VCl CI 65 0 fii) K, R R KOEt I EtOH, 61-73% 5240% t 66 Iodovinyl epoxides have been prepared from treatment of a-allenic alcohols with iodine, followed I92 Contemporaiy Urganic Synthesisby base-induced epoxide formation.36 For example, iodination of 67 gave the intermediate diiodide 68, which on treatment with sodium hexamethyldisilazide then generates the epoxide 69 predominantly as the trans-isomer shown.NaN(TMS)2 THF, 0°C 93% overall 1 A p”--~ H I 69 Of numerous reports detailing the use of molecular oxygen as oxidant, the work of Mukaiyama and his group is particularly noteworthy. In recent work they have demonstrated that acid-sensitive epoxides can be prepared via oxygenations of olefins in the presence of a cobalt cataly~t.”~ Propionaldehyde diethyl acetal, which is also added to the reaction mixture, acting as a reductant, is converted into ethyl propionate and ethanol, the reaction therefore occurs under neutral conditions; the synthesis of the epoxide 71 from the olefin 70 is typical.I 71 OEt 76% 70 Singlet molecular oxygen has been used in the epoxy-hydroxylation of allylic alcohols catalysed by titanium tetraisopr~poxide.’~ Thus, conversion of the allylic alcohol 72 into the hydroxy epoxides 75 and 76 is achieved in one-pot via the hydroperoxides 73 and 74, and with very high diastereo~electivity.”~ A similar procedure beginning with vinyl stannanes 77 leads to the stannyl epoxides 79 through the intermediacy of the corresponding hydroperoxide 78.40 OH ‘02, TPP, hv CCb, O”C, 4 h 72 77 R=H,alkyl 78 T~(oP~’), 2445% overall 1 79 3 Oxetanes The photocycloaddition of olefins and carbonyl compounds (Paterno-Buchi reaction) continues to be the main method of choice for the synthesis of oxetanes.Bach has demonstrated that /)-alkylsubstituted silyl enol ethers undergo remarkably regio- and stereo-selective additions to aryl aldehydes, e.g. formation of the oxetane 82 from benzaldehyde (80) and the enol ether 81.4’ Ciufolini and co-workers have examined the Paterno-Buchi reaction of henzoquinones and olefins, and have shown that alkylidenecyclohexanes 84 react with para-benzoquinone (83) in good yield to give the regioisomeric oxetanes 85 and 86 in the ratio shown.4’ Interestingly, with smaller ring alkylidenes the regioisomeric preference is reversed, whereas acyclic olefins react with little regioselectivi ty.43 0 OTMS PhH 82 (91% d.s.) 80 81 4 0 83 + X R 84 = CH2, NTs = alkyl hv PhH 60-90% ___c X f$ R 0 +R5j 85 86 >7 1 The reactions between chloranil (87) and a,/)-unsaturated carbonyl compounds have also been investigated and proceed in good yield, generating tra~s-oxetanes.~~ For example, irradiation of a benzene solution of chloranil with ethyl cinnamate isomers 88 leads to the oxetane 89 in excellent yield.Bums: Saturated oxygen heterocycles 1930 0 87 88 I C0,Et 89 The research groups of both R a ~ a l ~ ~ and Gleiter46 have examined the use of oxetane 91, derived from the Paterno-Buchi reaction of the norbornene 90, in synthesis. Thus, Rawal and Dufour have transformed the simple norbornene 90 (X = H2) into the diquinane 92 in only four while Gleiter and Sigwart have prepared 'stellatriene' 93 in three steps from the oxetane 91 (x = C H ~ ) .~ ~ 91 92 93 Craig and Munasinghe have synthesized keto- oxetanes via intramolecular trapping of an oxonium ion.47 The reaction proceeds with high stereoselectivity, as shown for the synthesis of 95 from the sugar-derived silyl enol ether 94. This work has also been extended to the synthesis of the analogous tetrahydrof~rans.~~ W O V 94 95 4 Five-membered rings 4.1 Tetra hydro fur an s The synthesis of substituted tetrahydrofurans via free radical chemistry continues to be an active area of research. Rai and Collum have demonstrated that the radical cyclization of the ether 96 to the tetrahydrofuran 98 proceeds under aqueous conditions via in situ reduction of the tin species 97 with sodium borohydride in the presence of the initiator 4,4'-azobis(4-cyanovaleric acid) (ACVA).49 Udding et al.have introduced the copper(1) catalyst 100 for chlorine-transfer radical cyclizations, as shown for the synthesis of the diastereomers 101 from 99.50 A chromium species, generated from chromium(r1) acetate and various reducing agents such as LiAlH4, has also been used for the generation of carbon-centred free-radicals in tetrahydrofuran synthesis.51 c NaBH,, HS, KOH ACVA 90°C 6% I Me' 98 Br 96 101 Burke and Jung have demonstrated that treatment of the alkyne 102 with thiophenol under radical conditions leads to the tetrahydrofuran diastereomers 104 presumably through the intermediacy of the alkoxymethyl radical 103." Rawal and co-workers have reported on the generation and use of simple alkoxymethyl radicals in tetrahydrofuran synthesis, e.g.in the synthesis of the spirocycles 106 and 107 from the selenide 105.53 102 103 178% CgPh CO,Bu' 104 (2 : 1 trans : cis) G 105 Bu",SnH, AIBN PhH, A 95Y0 1 a--- 4.3 + =a- 1 106 1 07 A review containing 90 references on synthetic routes to 2,5-disubstituted tetrahydrofurans has been p~blished.'~ Walkup and Kim have prepared I94 Contemporary Organic Synthesisthe 2,5-disubstituted tetrahydrofuran lower portion of the panamycin group of macrolides via the cyclization of y-silyl~xyallenes.~' Thus, treatment of the chiral allene 108 with mercury(I1) triflate, and subsequent carbonylation of the intermediate organomercurial gave the tetrahydrofuran 109, predominantly as the cis-diastereomer shown.In a related process y-oxoallenes have been shown to cyclize solely under the palladium-catalysis conditions of the carbonylation; for example, the formation of the furanoside 111 from the allene 1 1 0 . ~ ~ OTMS M * ~ O + - . = j 1 08 (i) Hg(OCOCF&, CH2C12 I (ii) CO, MeOH. PdCI2, CuC12 I A0 57% Me0 I 109 (90% d.e.) MeoYo MeOH, PdCIz, CO(1 CUCI~, atm.) c %OMe 110 111 OEt 442 Furanosides can also be prepared by a catalytic oxidation procedure of homoallylic alcohols.57 In this process substituted homoallylic alcohols 112 are oxidized by molecular oxygen, catalysed by the in situ prepared palladium complex 113, to the products 114. hR1 R2 112 R' = a!@[, ptwnyl R2 = alkyl Pd(N02)CI(MeCN)2 113 cUcl2, R~OH 02,55"C, 2 h 56-10090 R2 114 R3 = Pi, Bu' A number of research groups have reported on the synthesis of 2-hydroxymethyl substituted tetrahydrofurans via an intramolecular epoxide-ring opening process.For example, Ley and co-workers have prepared the tetrahydrofuran portion of the antibiotic tetronasin via epoxide ring-opening of the chiral epoxide 115 following desilylation of the protected secondary hydroxyl, giving the tetrahydrofuran 116 as one diastereomer in excellent yield. In a synthesis of (+)-tuberine, Taber et al. have used the intramolecular ring-opening of an epoxide to form the tetrahydrofuran portion of this natural product." Thus, Sharpless asymmetric dihydroxylation of the olefin 117 afforded, in one step, the chiral tetrahydrofuran 118 in good yield. Similarly, Panek, Garbaccio, and Jain have demonstrated that epoxidations of the bis- homoallylic alcohols 119 generate the tetrahydrofurans 121 with excellent diastereoselectivity, via the intermediacy of the epoxide 120.60 H N Br ADmb Q acetone 65% - BU'OH-HpO 117 118 R 9 OH Or* dPBA [+] VO(acac12 Me26iPh 20-81 TBHP Yo Me2!%Ph 119 120 I PhMe2Si ,R n 121 Interestingly, cyclopropanation of the isomeric alkenes 122, followed by treatment of the derived cyclopropanes 123 with catalytic acid generates the related tetrahydrofurans 124 with excellent diastereoseIectivity.'* Corey has also used an intramolecular cyclopropane ring-opening in a biomimetic synthesis of 12-desoxy-glycinoeclepin (127), wherein exposure of the cyclopropane 125 to excess boron trifluoride etherate gives the bridged tetrahydrofuran 126.6' R R Me2SiPh 67-8196 Me2SiPh 122 123 CH$& 1 r.t.pTSA 7446% PhMe&i TR 124 OH j A biomimetic approach to the polyether antibiotic etheromycin has been reported by Paterson and his group, whereby an acid induced cascade reaction of the diepoxide 128 led to the bis-tetrahydrofuran 129 in moderate yield.62 Mukai et al. have reported a B q p y O H OTBS Bun;imF- B m i . ; ; 115 116 Burns: Saturated oxygen heterocycles 195*'OH 126 ;ir9y' CO2H 127 synthesis of 3-hydroxytetrahydrofurans using an epoxide ring-opening pro~ess.~' In this reaction exposure of the epoxides 130 to catalytic boron trifluoride etherate generates the tetrahydrofurans 131 in good yield and with excellent diastereoselectivity; cis-epoxides are transformed into cis-tetrahydrofurans, while the trans-isomers give the trans products. Interestingly, complexation of the acetylene in 130 with COz(CO), prior to tetrahydrofuran formation reverses the stereoselect ivi ty.1 28 aq. HCI THF, 28"C, 30% 1 OBZ 0 OPMB OH 129 R FaB.OEt2 CH2C12 44-9846 R R = SiMe3, Br, Ph 1 30 131 Iodocyclizations also continue to be an attractive route to functionalized tetrahydrofurans. Knight and his research group have prepared annulated tetrahydrofurans via this route, and have shown that the reaction is highly stereoselective, as shown for the synthesis of the cis-tetrahydrofuran 133 from the cis-olefin 132.- Alteration of the electron- withdrawing effect of the nitrogen protecting group in the aminoalkenes 134 has a profound effect on the stereoselectivity of the iodocyclized products; the electron-withdrawing substituents force the reaction to run under electronic control giving predominantly cis-products 135, as opposed to trans- products 136 which arise through steric control.65 U + 1 35 136 NaHC03, Hfl ,34 Etfl or EtOAc 0°C R=SO&Fa 93 7 R = COPh 30 70 Stereoselective iodocyclizations have been used in a number of natural product syntheses over the review period, such as in the synthesis of the C1,-CZz subunit of ionomycinp6 the synthesis of m ~ s c a r i n e , ~ ~ and in the synthesis of the tetrahydrofuran portion of the marine natural product halichondrin B.68 In this latter work, the secondary triethylsilyl ether of 137 is cleaved in the cyclization reaction to give after acid treatment predominantly the tetrahydrofuran isomer 138 shown.TBDPSO 137 (i) 12, NaHCO3 (ii) IN HCI I PMB OH H d 138 A number of publications concerning syntheses of annulated tetrahydrofurans have appeared recently. Thus, Koreeda and co-workers have reported a highly efficient synthesis of the tetrahydrofuran 140 from the aldehyde 139 in a formal synthesis of aflatoxin B2."" Similar compounds have been prepared by a photolytic route, as shown in the preparation of the acetals 142 from the cyclobutanone 141." 196 Contemporary Organic SynthesisSEMO CHO SEMO OTBDMS a q . ~ ~ THF, r.t. MeO MeO 139 140 Me 56% Me 141 142 Overman and his group have prepared the annulated tetrahydrofuran 144 with high diastereoselectivity via methanolysis of the unsaturated lactone 143 in a synthesis of the marine natural product kumausallene 145.'' 0 & .,/OBz H 143 H H 144 145 Mikami and co-workers have prepared the furofuran-containing natural product neopaulownin 148 via a stereoselective ene reaction of the ether 146 to give the trans-tetrahydrofuran 147, which was then converted into the natural product 148 through regioselective olefin epoxidation, reductive double bond cleavage, and acid-catalysed epoxide ring- opening." The related natural product asarinin has been prepared by Takano and co-worker~.'~ In this work they found that treatment of the dioxepin 149 with a Lewis acid, followed by a reductant, gave the diastereomers 150 and 151, the ratio being dramatically affected by the choice of reagents.been reported by Hojo et al. wherein an in situ generated carbonyl ylide reacts with activated double bonds.74 Thus, treatment of the trimethylsilylmethyl ether 152 with fluoride ion, in the presence of dimethyl fumarate generated the tetrahydrofurans 154 as essentially a 1 : 1 mixture of diastereomers at the two position, presumably through the intermediacy of the ylide 153.A cycloaddition approach to tetrahydrofurans has 146 147 (i) mCPBA (ii) 0% then NaBH, (iii) pTSA, 30% overall 148 &pc5H11 149 (i) Lewisacid (ii) reductant, 2745% 0 150 151 (PSO),TiCI,-NaBH, 30 : 1 lBSOTf-NaBH4 1 : 25 152 153 (81%) ~M-.cri""e Ar 154 Bums: Saturated oxygen heterocycles 197An alternative [3 + 21 cycloaddition approach to tetrahydrofurans has also been p ~ b l i s h e d . ~ ~ In this process, tin tetrachloride promoted addition of an ally1 silane such as 156 to the a-keto ester 155 gives the intermediate 157 which, after a 1,241icon shift, affords the tetrahydrofuran 158 in excellent yield and high diastereoselectivity.Functionalized allylsilanes have been used in an alternative synthesis of tetra hydro fur an^.^^ In this work, the oxocarbenium ions 161, formed by the reaction between the allylsilanes 159 and the acetals 160, undergo an intramolecular Sakurai reaction to generate the all-cis tetrahydrofurans 162 in moderate to excellent yield. YsiMe2Ph 156 SnCI, P h G o E t 0 CH&12. 82% r.t 155 157 Em&-- Ph - 0 ’SiMe2Ph 158 R2 ‘o+ I R’-R2 = alkyl 14143% R2P 162 Bridged tetrahydrofurans have been prepared via the intermediacy of oxonium ylides as shown for the synthesis of the compounds 165 and 166.77 In this reaction, the ether oxygen adds to the rhodium carbenoid generated from the diazo compound 163 and rhodium acetate, giving the oxonium ylide 164, which then undergoes a Stevens [ 1,2]-shift leading to the product tetrahydrofurans in the ratio shown.tetrahydrofurans such as 168 can be obtained from sugar-derived 1’- and ii-lactones bearing ring triflates by treatment with acidic lactone 167 was converted into the tetrahydrofuran 168 in 93% yield, with clean inversion occurring at the carbon bearing the triflate moiety. A similar base-induced rearrangement has also been reported for the synthesis of analogues of m~scarine.’~ Finally, highly functionalized chiral Thus, the L 163 1 165 166 15-19 : 1 OH 167 168 4.2 Dihydrofurans The dihydrobenzofuran 170, which is an intermediate in a formal synthesis of (+)-morphine, has been formed in one step from the bicycle 169 via a tandem intramolecular Heck insertion/ heterocyclization reaction disclosed by Overman and Hong.80 MeO P OH / 169 170 This report follows an earlier total synthesis of both antipodes of morphine by Overman’s group where the dihydrofuran 173 was constructed in a separate step after Heck-cyclization of 171, via ring-opening of an in situ prepared epoxide derived from 172, as depicted in Scheme 2.8’ In work also directed towards the synthesis of morphine, Parker and Fokas have reported that the aryl bromide 174 undergoes free-radical cascade cyclization to produce the tetracycle 175 exclusively as the diastereomer shown.82 Grubbs and his research group have continued their work on the use of transition metal complexes 198 Contemporary Oiganic Synthesis2,3-Dihydrofurans have been prepared via a different route, also through the intermediacy of carbene complexes, in a novel cyclization of homopropargylic alcohols.85 Thus, treatment of the homopropargyllic alcohol derivative 182 with molybdenum hexacarbonyl and trimethylamine N- oxide (TMNO) in ether and triethylamine as solvents generates the dihydrofuran 183 in 52% yield.An in situ generated free-carbene has also been used in the synthesis of 2,3-dihydrof~rans.~~ In this work, lithium trimethylsilyldiazomethane 185 reacts with P-trimethylsilyoxyketones 184 to generate 2,3-dihydrofurans 187, presumably through the intermediacy of the carbene 186.Me0 6Bn 171 1 e, PhMe, 120°C. 60% 10% Pd(OCOCF&oh3P)2 goMe OBn DBS-N f d d 3 172 - Mo(CO)s, TMNO EtsN, Et20 20 "C (0 FsB.OEt2. EtSH, 79% , CSA, CH2Cl2, 0°C (ii) OZN -Q"OsH 60% NO2 182 52% 183 DBS= $ overall 1 84 R' ,R* = altcyl R3 = alkyl, aryl 186 I DBS-N OH 1 73 TMS R3 187 Scheme 2 There have been numerous reports over the review period concerning the use of furan as the diene in Diels-Alder reactions, generating bridged dihydrofuran products for use in natural product synthesis. Corey and Loh report that the H H oxazaborolidene 189 is an effective catalyst for the enantioselective reaction of furan with 2-bromo- or ____t Bu3SnH Me0 0 AIBN, 140°C *'C02Me C02Me 6% 174 1 75 2-chloro-acrolein 188.87 The products 190 are in ring-closing metathesis reactions.Thus, they report that the ruthenium carbene 177 smoothly converts the acyclic diene 176 into the dihydrofuran 178 at room temperature,x3 and that the molybdenum carbene 180 catalyses the metathesis of enol ethers such as 179, leading to dihydrofurans such as 181.84 formed in greater than 98% yield, with excellent stereoselectivity (exolendo = 99/1), and high enantioselectivity. 0 =(" CHO + / \ JOTPh (yPh CHS12, -78°C > 98% 84% 190 X = Br 92% 8.8. X = CI 90% 8.8. 188 X = CI, Br 1 76 178 The Diels-Alder reaction between furan and the chiral cephalosporin triflate 191 generated the RO Ro:Mo+ ! Ph bridged dihydrofuran 193, presumably through in situ formation of the cyclic allene 192.88 179 pentane, r.t., 81% 181 the Diels-Alder reaction across the 3,4 position.Pha P h J o L R 5 CMe(CF& 180 c o Ph Interestingly, the corresponding sulfide undergoes Burns: Saturated oxygen heterocycles 1990- PtCHZCONH 0 COPPMB 191 192 I 0- C02PMB 193 De Meijere and his group have studied the Diels- Alder reaction between substituted furans and the cyclopropylidene 194 as part of a programme directed toward the synthesis of the sesquiterpene illudin M.'" For example, reaction of 194 with the furan 195 occurs with complete regioselectivity, to generate the ex0 and endo adducts 196 and 197 respectively in the ratio shown. 194 195 neat 20°C. 76% 1 e 2 M e + l o . Q"'" 196 197 1-5 1 An approach to the dihydrobenzofuran natural product r-viniferin which proceeds via a [5 + 21 cycloaddition has been reported by Engler et al."" In this work polarized, nucleophilic stilbenes such as 198 react with benzoquinones 199 in the presence of stannic chloride to give, via the carbocation intermediate 200, the trans product 201.Marshall and Pinney have disclosed a stereoselective synthesis of 2,5-dihydrofurans involving cyclization of a stereoselectively formed allenyl carbinol.'" The allenyl carbinols, such as 203, were formed with high stereoselectivity by SN2' addition of lithium dimethyl cuprate to chiral propargylic epoxides such as 202, and after selective silylation underwent smooth cyclization to 0 199 R=H,Me SnCI,, CH&12, -78°C Cl, 1 200 R = H 73% R=Me 82% I 201 dihydrofurans, as shown for the preparation of 204. Hydride, as opposed to cuprate addition has been used in the synthesis of the furan-containing macrocycles found in natural products of the pseudopterane family."* HO ;c" Me2CuU Hk > ___t THF 75% MOMOF" OMOM OH 202 203 d.e.> 95% (i) TBDMSCI, NEtS CH2Cb, 90% (ii) AgNO,, H@/acetone, 86% OTBDMS I \ 204 The manganic acetate promoted addition of P-diketones to enynes usually produces a mixture of furan and dihydrofuran products depending on substitution on the enyne. Melikyan et al. have now shown that the triple bond of enynes can be protected with the dicobalt hexacarbonyl group, thus forcing the reaction to occur exclusively at the alkene, as depicted for the synthesis of the dihydrofuran 207 from the complexed enyne 205 and the P-ketoester 206."-? Mellor and Mohammed have used manganic acetate promoted additions of P-diketones to enol ethers to generate spirocyclic corn pound^"^ and annulated dihydr~furans.'~ In this latter work, annulated dihydrofurans related to the aflatoxins have been prepared: for example, reaction of the dihydrofuran 208 with dimedone (209) produces the dihydrofuran 210.200 Contemporary Organic Synthesis0 205 206 (i) 4 eq. Mn(OAc)3, AcOH, 30°C 1 (ii) (NH4L$l(N0,)6 0 Mn(OAc)3 AcOH, 60°C 0 40% 208 209 21 0 An entirely different approach to the dihydrofuran ring of annulated dihydrofurans, employing an oxaza-Cope rearrangement has been reported by Civitello and Rapoport.'" In this work (Scheme 3) the chiral oxime 211 undergoes the acid-catalysed oxaza-Cope rearrangement to give the lactam 212, which can be converted into the dihydrofuran 213 by treatment with methanolic HCI.The annulated systems 214 and 215 are obtained in the ratio shown by debenzoylation and intramolecular acetal formation. OTs J: TsO 21 1 C02Me OBz &: MeOH HCI so TsO 0 TsO 21 3 (i) K&05MeOH (ii) HCI J 67% overall 212 + TsO TsO ' 0 'H 214 21 5 (1.6 1) Scheme 3 Trost and Shi have reported a synthesis of the natural product solamin 218 using a Ramberg- Backlund reaction of the in situ generated a-chlorosulfone derived from 216 to produce the dihydrofuran 217.'7 216 (i) Bu'OK, Bu'OH, CCI,, r.t., 65% (ii) TsOH, H@. EtOH, r.t.. 95% HO-. C12H23 A. HO 1 21 8 Finally, a base-induced rearrangement of 3-methylenetetrahydrofurans has been shown to be an efficient method for the preparation of fused 2,5-dihydrof~rans.'~ For example, treatment of the methylene tetrahydrofuran 219 with potassium t- butoxide in DMSO affords the product dihydrofuran 220 in good yield.&-& I 60-80 "C I 219 220 5 Six-membered rings 5.1 Tetrahydropyrans Of the numerous methods available for the synthesis of tetrahydropyrans, electrophile induced ring closure processes continue to be one of the favourite routes to this ring system. For example, while cyclization of the spirocyclic oxindole derivative 221 could not be effected under iodo- or bromo-etherification conditions, recourse was made to an intramolecular oxymercuration reaction which, after organomercurial reduction, gave the complex tetrahydropyran 222, an advanced intermediate in the synthesis of gelsemine."" In other work directed towards the synthesis of gelsemine Johnson and co-workers have formed the tetrahydropyran derivative 224 by treatment of the tricycle 223 with silver acetate and iodine.'"" Construction of the c-ring in forskolin has been examined by Welzel and his group, who have shown that while treatment of 225 with N-phenylseleno- Bums: Saturated oxygen heterocycles 201221 NMe2 I (ii) NaBH,, NaOH.CH2C12, EtOH 48% overall J 222 phthalimide gives the anti-product 226, treatment with mercury triflate leads to 227, the product of syn-addi t ion. 0- OH AgOAc, I2 .____L AcOH 0 AcO 223 224 (p '*, H 0 225 The dioxadecalin 231 has been prepared from the sugar-derived epoxide 230 via an acid-induced epoxide-ring opening, as part of the total synthesis of hemibrevetoxin B. been employed in the synthesis of related dioxadecalin ring systems.t043tos 6-endo Ring-closure has also been shown to operate in the epoxide ring- opening of cobalt-complexed propargylic epoxides. ' O 6For example, complexation of the trans- propargylic epoxide 232, followed by treatment with boron trifluoride etherate, gave almost exclusively the cis-tetrahydropyran 233. Similar approaches have 230 M e 0 2 C d OBn H H H 231 (i) CO~(CO)~, CH&I,, r.t. tii) F3B.0Et2, CH2CI2, -78°C 96% ph' 232 233 Intramolecular hetero-Michael addition has also been used for the preparation of tetrahydropyrans as shown for the preparation of the dioxadecalin 235 from the a,/?-unsaturated ester 234.1°7 A fluoride ion induced Michael addition has been used as the ring-forming step in an asymmetric synthesis of the cholesterol biosynthesis inhibitor decarestrictine L, as shown in the transformation of the acyclic ketone 236 into the tetrahydropyran 237.1°8 NaH THF, -36°C ZQWe HgOTf _____c 226 227 A number of research groups have used intramolecular epoxide-ring opening reactions to form complex tetrahydropyrans in the synthesis of natural products. Thus, Roush and Marron have prepared the tetrahydropyran 229 from the epoxide 228 via fluoride ion induced desilylation, as part of a programme directed toward the synthesis of the mycalamide family of antibiotics.lo' OTBDPS L_ I MeCN 9WO OH C>Me 228 229 234 235 p O M 60°C 11% 236 O A 237 An alternative route to this ring substitution has been reported by Clark and Whitlock who have demonstrated that copper-catalysed decomposition of the diazoketone 238 affords the tetrahydropyrans 239 and 240 in the ratio shown."'" The use of 202 Contemporary Organic SynthesisY l copper hexafluoroacetylacetonate in this process had been shown in previous work to promote insertion of the in situ formed copper carbenoid into the allyl ether oxygen in preference to CH- MeAICI,, 246 -78OC - n=m CH2C12 insertion.' lo 245 63% 247 238 CU(CF&OCHCOCF& CHS12, A, 6890 I --- + -*-ate H H 239 240 77 23 PhMe/pentane.-100"C, 70-8596 OH R , XI\\ NaHiDMSO- : - THF V ' C I 7 H 5 % 249 (-98% e.e.) R = alkyl 250 (8598% e.e.) As part of an investigation into tetraene cyclizations, Takacs and Chandramouli have shown 5.2 Dihydropyrans that treatment of the tetraene 241 with catalytic palladium( 1 1 ) leads to the olefinic tetrahydropyran 242 in good yield.' ' ' Palladium catalysis has also been used in a highly stereoselective preparation of spirocyclic tetrahydropyrans from dienes, eg.in the transformation of the diene 243 into the tetrahydropyran 244. ' " E : F 3 \ \ 24 1 Pd(OAc)z, PPh3 THF, 65"C, 82% 1 Et02C E t 0 2 G \/.*-A 242 0 Li&03 HOAclacetone 243 81 % 244 Lactols have been shown to undergo an intermolecular ene reaction generating trans- 2,6-disubstituted tetrahydropyrans with high stereoseleetivity.' I Thus, exposure of the lactol ether 245 to methyl aluminium dichloride followed by addition of the olefin 246 gave the truns product 247 in good yield. cis-2,3-Disubstituted tetrahydropyrans 250 have been prepared in high optical purity from the chlorohydrins 249, themselves prepared in high optical purity by the reaction between chiral allyl boronates 248 and aldehydes.' l 4 There have been numerous reports over the review period concerning the synthesis of dihydropyrans via hetero Diels-Alder reactions, and a review containing 1 1 1 references concerned with the asymmetric variant of this reaction has been published.' I s Yamamoto and his research group have shown that in situ prepared borane complexes derived from tartaric acid (such as 252) catalyse the reaction of oxygenated butadienes such as 251 with benzaldehyde to give pyrones, e.g. 253, in high optical purity after treatment with acid.' I 6 Motoyama and Mikami have demonstrated that the boron complex 256 also catalyses the Diels-Alder reaction of siloxydiene 254 and methyl glyoxylate (255), giving the pyrone 257, again after acid treatment of the adduct, in good yield and in high optical purity.'" OMe 251 + 252 c MeCH2CN, -78°C PhCHo (ii) CF3CO&l, 950/.0 QPh 253 (97% e.e.) A stereoselective synthesis of precursors to the natural products robustadial A and B has been published, which employs a regioselective hetero Diels-Alder reaction. ' '' Thus, Knoevenagel condensation of the 1,3-dione 258 and the aldehyde 259, in the presence of (S)-P-pinene (261) affords the spirocyclic product 262, presumably through the intermediate 260. Tietze and his co-workers have used a similar approach in the synthesis of the tricycles 265 from the reaction of aldehydes 263 and the dione 264, the trans products always being formed as the major isomer.'" Burns: Saturated oxygen heterocycles 203p” acrolein, 269) and ao-methylene compounds such as 270.12’ TMSO 258 PhMe, -78°C .‘C02Me 254 + 0 (ii) CF3CO$i,69% 0 II HKC02Me 255 To Me0& 0 258 KOAc + ____e 3A sieves HOAc 259 257 (94% e.e.) Ma2cY 260 IB 1 261 (80% overall) 262 263 264 R = alkyl 265 The highly stereoselective hetero Diels-Alder reactions of sulfonyl-a, P-unsaturated alkenes have been published by Wada et aZ.120 They have shown that various Lewis acids catalyse the reaction of a,B-unsaturated alkenes 266 with ethyl vinyl ether 267, as shown for the synthesis of 268.0 R \ 4 S O 2 P h R = alkyl 268 Spirocyclic dihydropyrans, such as 271, have been formed with high stereoselectivity by the Lewis acid catalysed reaction of a, P-unsaturated aldehydes (e.g.271 Samarium diiodide has also been shown to catalyse hetero Diels-Alder reactions,’22 and recent work by Grieco and Moher has demonstrated that lithium perchlorate in diethyl ether promotes the reaction between amino aldehydes and oxygenated dienes. 123 For example, reaction of the aldehyde 272 and the diene 273 leads to the pyrone after acid treatment, predominantly as the threo isomer 274 shown. Synthesis of the dihydropyrans 277 and 278 has been achieved in excellent yield by hetero Diels- Alder reaction in water between the diene 275 and glyoxylic acid 276.124 4 C H O HNBoc ( i ) 0.5MLc104, Etg, r.t. 74% 272 + OMe (ii) HCI (aq.) 0 HNBoc AOTBDMS 273 274 + 100°C -100% C02H 277 278 64 36 A number of significant publications concerning alternative routes to dihydropyrans and related systems have also been published recently.Paterson and Smith have prepared the chiral pyrone 280 from the alcohol 279 by a Lewis acid promoted Michael addition-elimination procedure125 as part of a total synthesis of the marine macrolide (-)-preswinholide An efficient synthesis of trans-3-hydroxyflavanones 282 from a base- promoted ring closure of the epoxides 281 has been reported, the epoxides themselves coming from dimethyl dioxirane epoxidation of the corresponding olefins. 127 Mark6 and Bayston have reported on the use of the intramolecular silyl-modified Sakurai reaction in the synthesis of 3,4-dihydro~yrans.’~” Thus, a trimethylsilyl triflate induced reaction between the 204 Contemporary Organic SynthesisBzoTc' 0 279 TMSOTf P&NEI CH2C12 -78"C+20"C 61 % BzoT 0 0 281 R = alkyl, alkoxy, chloro Bu4NOH CH&I+i20.r.t. I 0 282 280 olefin 283 and the aldehyde 284 generates the dihydropyran 285 solely as the cis isomer, in excellent yield. T M S T A TMSO 283 + dH TMSOTf -78°C +20°C 87% c CH$b CP 285 284 Hoveyda and co-workers have reported a very useful kinetic resolution of 3,4-dihydropyrans using a zirconium-mediated carbomagnesation process. '29 For example, when the racemic pyran 286 is treated with ethylmagnesium bromide and the chiral zirconium complex ( EBTHI)ZrCI2, recovered starting material of exceptionally high optical purity (287) is obtained when the reaction is stopped after 60% conversion. om 286 (R)-(EBTHI)ZrCI, EtMgCI, THF I om 287 (> 99% e.e.) 2,3-Dihydropyrans have been prepared from sugar derived lactones via Grignard additions to the lactone carbonyl groups and subsequent dehydration of the hemiketals so formed, e.g.the preparation of 289 from the lactone 288.130 A two-step route to 6-chiral-2,3-dihydropyrans has been reported by Jacobs and Gopalan, also involving dehydration of an intermediate hemiketal.l3I For example, deprotonation of the chiral sulfone 290 generated the lacto1291 (as a mixture of diastereomers), which was then dehydrated to give the dihydropyran 292 in good yield. (i) PhMgBr, THF OBn CH2C12, r.t. OB" 86% 288 289 0 LHMDS h S O 2 T o l THF, -78°C 56% 6 290 References 291 rcl S02T0l 292 1 B.D. Brandes and E.N. Jacobsen, J. 01%. Chem., 1994, 59, 4378.2 S. Chang, N.H. Lee, and E.N. Jacobsen, J. Org. Chem., 1993, 58, 6939. 3 S . Chang, J.M. Calvin, and E.N. Jacobsen, J. Am. Chem. SOC., 1994, 116, 6937. 4 H. Sasaki, R. hie, and T. Katsuki, Synlett, 1993, 300; H. Sasaki, R. Irie, and T. Katsuki, Synlett, 1994, 356. 5 N. Hosoya, R. Irie, and T. Kdtsuki, Synlett, 1993, 261. 6 N. Hosoya, A. Hatayama, K. Yanai, H. Fujii, R. Irie, and T. Kdtsuki, Synlett, 1993, 641; T. Hamada, R. hie, and T. Kdtsuki, Synlett, 1994, 479. 7 R. Irie, N. Hosoya, and T. Katsuki, Synktt, 1994, 255. 8 K. Imagawa, T. Nagata, T. Yamada, and T. Mukaiyama, Chem. Lett., 1994, 527. 9 B.B. De, B.B. Lohray, and P.K. Dhal, Tetrahedron Lett., 1993, 34, 2371. 10 J.A.M. De Bont. 7ktruhedron: Asymmetry, 1993, 4, 1331. 11 E. J. Allain, L.P.Hager, L. Deng, and E.N. Jacobsen, J. Am. Chem. Soc., 1993, 115,4415. 12 P. Besse, M.F. Renard, and H. Veschambre, Tetrahedron: Asymmetry, 1994, 5, 1249. 13 P. Besse and H. Veschambre, Tetrahedron: Asymmetry, 1993, 4, 1271. 14 D.H.G. Crout, V.S.B. Gaudet, and K.O. Hallinan,J. Chem. SOC. Perkin Trans I , 1993, 805. 15 A. Koch, J.-L. Reymond, and R.A. Lerner, J. Am. Chem. Soc., 1994, 116, 803. Bums: Saturated oggen heterocycles 20516 E.J. Corey and C.J. Helal, Tetrahedron Lett., 1993, 34, 17 T. Chan, L.M. Chen, D. Wang, and L.H. Li, Can. J. 18 V.K. Aggarwal, H. Abdel-Rahman, R.V.H. Jones, 5227. Chem., 1993, 71, 60. H.Y. Lee, and B.D. Reid, J. Am. Chem. SOC., 1994, 116,5973. 19 V.K. Aggarwal, M. Kalomiri, and A.P. Thomas, Tetrahedron: Asymmetry, 1994, 5, 723.20 K. Maruoka, A.B. Concepcion, and H. Yamamoto, Synlett. 1994, 521. 21 W. Adam, J. HalBsz, A. Lkvai, C. Nemes, T. Patonay, and G. Toth, Liebigs Ann. Chem., 1994, 795. 22 A.L. Baumstark and D.B. Harden, J. Org. Chem., 1993,58, 7615. 23 W. Adam, G. Kib, and M. Sauter, Chem. Ber., 1994, 127, 433; W. Adam and M. Sauter, Liebigs Anti. Chem., 1994, 689. 24 W. Adam, L. Hadjiarapoglou, K. Peters, and M. Sauter, J. Am. Chem. SOC., 1993, 115, 8603. 25 W. Adam, M. Sauter, and C. Ziinkler, Chem. Ber., 1994, 127, 1 1 15. 26 W. Adam, F. Prechtl, M.J. Richter, and A.K. Smerz, Tetrahedron Lett., 1993, 34, 8427. 27 M. Kurihara, S. Ito, N. Tsutsumi, and N. Miyata, Tetrahedron Lett., 1994, 35, 1577. 28 A. Armstrong, P.A. Barsanti, P.A. Clarke, and A. Wood, Tetrahedron Lett., 1994, 35, 6155.29 A. Albeck and R. Persky, J. Org. Chem., 1994, 59, 653. 30 S. Romeo and D.H. Rich, Tetrahedron Lett., 1994, 35, 31 A. Albeck and R. Persky, Tetrahedron, 1994,50,6333. 32 J. Barluenga, B. Baragafia, A. Alonso, and J.M. Concellbn, J. Chem. SOC., Chem. Commun., 1994, 969. 33 J. Barluenga, L. Llavona, P.L. Bernad, and J.M. Concellon, Tetrahedron Lett., 1993, 34, 3 173. 34 S. Florio and L. Troisi, TEtrahedron Lett., 1994, 35, 3175. 35 K. Mallaiah, J. Satyanarayana, H. Ila, and H. Junjappa, Tetrahedron Lett., 1993, 34, 3145. 36 R.W. Friesen and M. Blouin, J. Org. Chern., 1993, 58, 1653. 37 K. Yorozu, T. Takai, T. Yamada, and T. Mukaiyama, Chem. Lett., 1993, 1579. 38 W. Adam and B. Nestler, Angew. Chem., hit. Ed. Engl., 1993, 32, 733. 39 W. Adam and B. Nestler, J.Am. Chem. SOC., 1993, 115, 7226. 40 W. Adam and P. Klug, Chem. Ber., 1994, 127, 1441. 41 T. Bach, Tetrahedron Lett., 1994, 35, 5845. 42 M.A. Ciufolini, M.A. Rivera-Fortin, and N.E. Byrne, Tetrahedron Lett., 1993, 34, 3505. 43 M.A. Ciufolini, M.A. Rivera-Fortin, V. Zuzukin, and K.H. Whitmire,]. Am. Chem. Soc., 1994, 116, 1272. 44 J.-H. Xu, L.-C. Wang, J.-W. Xu, B.-Z. Yan, H.-C. Yuan, J. Chem. Soc., Perkin Trans I , 1994, 571. 45 V.H. Rawal and C. Dufour, J. Am. Chem. Soc., 1994, 116. 2613. 46 R. Gleiter and C. Sigwart, J. 0%. Chem., 1994, 59, 1027. 47 D. Craig and V.R.N. Munasinghe, J. Chem. Soc., Chem. Commun., 1993,901. 48 D. Craig, M.W. Pennington, and P. Warner, Tetrahedron Lett., 1993, 34, 8539. 49 R. Rai and D.B. Collum, Tetrahedron Lett., 1994, 34, 6221.50 J.H. Udding, C.J.M. Tuijp, M.N.A. van Zanden, H. Hiemstra, and W.N. Speckamp, J. Org. Chem., 1994, 59, 1993. 51 C. Hackmann and H.J. Schiifer, Tetrahedron, 1993, 49, 4559. 4939. 52 S.D. Burke and K.W. Jung, Tetrahedron Lett., 1994, 53 V.H. Rawal, S.P. Singh, C. Dufour, and C. Michoud, 54 J.-C. Harmange and B. FigadCre, Tetrahedron: 55 R.D. Walkup and S.W. Kim, J. Org. Chem., 1994, 59, 56 R.D. Walkup and M.D. Mosher, Tetrahedron, 1993, 57 T.M. Meulemans, N.H. Kiers, B.L. Feringa, and 35, 5837. J. Org. Chem., 1993, 58, 7718. Asymmetry, 1993,4, 171 1. 3433. 49, 9285. P.W.N.M. van Leeuwen, Tetrahedron Lett., 1994, 35, 455. 58 G.-J. Boons, D.S. Brown, J.A. Clase, I.C. Lennon, and S.V. Ley, Tetrahedron Lett., 1994, 35, 319. 59 D.F. Taber, R.S. Bhamidipati, and M.L.Thomas, J. Org. Chem., 1994, 59, 3442. 60 J.S. Panek, R.M. Garbaccio, and N.F. Jain, Tetrahedron Lett., 1994,35, 6453. 61 E. J. Corey and B. Hong, J. Am. Chem. SOC., 1994, 116, 3149. 62 I. Paterson, R.D. Tillyer, and J.B. Smaill, Tetrahedron Lett., 1993, 34, 7137. 63 C. Mukai, Y. Sugimoto, Y. Ikeda, and M. Hanaoka,]. Chem. Soc., Chem. Commun ., 1994, 1 1 6 1 , 64 J.M. Barks, D.W. Knight, and G.G. Weingarten, J. Chem. SOC., Chem. Commun., 1994, 719. 65 Y. Tamaru, H. Harayama, and T. Bando, J. Chenr. Soc., Chem. Commun., 1993, 1601. 66 Y. Guindon, C. Yoakim, V. Gorys, W.W. Ogilvie, D. Delorme, J. Renaud, G. Robinson, J.-F. LavallCe, A. Slassi, G. Jung, J. Rancourt, K. Durkin, and D. Liotta,J. Org. Chem., 1994, 59, 1166. 67 D.W. Knight, D. Shaw, and G. Fenton, Synlett, 1994, 295.68 K. Horita, M. Nagasawa, S. Hachiya, and 0. Yonemitsu, Synlett, 1994, 40. 69 M. Koreeda, L.A. Dixon, and J.D. Hsi, Synlett, 1993, 555. 70 A. Mittra, S. Biswas, and R.V. Venkateswaran, J. Org. Chem., 1993, 58, 7913. 71 T.A. Grese, K.D. Hutchinson, and L.E. Overman, J. Org. Chem., 1993, 58. 2468. 72 K. Mikami, H. Matsueda, and T. Nakai, Synlett, 1993, 235. 73 S. Takano, K. Samizu, and K. Ogasawara, Synlett, 1993, 785. 74 M. Hojo, M. Ohkuma, N. Ishibashi, and A. Hosomi, Tetrahedron Lett., 1993, 34, 5943. 75 T. Akiyama, K. Ishikawa, and S. Ozaki, Chem. Lett., 1994,627. 76 P. Mohr, Tetrahedron Lett., 1993, 34, 6251. 77 F.G. West, T.H. Eberlein, and R.W. Tester, J. Chem. 78 J.R. Wheatley, C.J.F. Bichard, S.J. Mantel!, J.C. Son, Soc., Chem. Commun., 1993, 2857.D.J. Hughes, G.W.J. Fleet, and D. Brown, J. Chem. SOC., Chem. Commun., 1993, 1065. 79 S.J. Mantell, P.S. Ford, D.J. Watkin, G.W.J. Fleet, and D. Brown, Tetrahedron, 1993, 49, 3343. 80 C.Y. Hong and L.E. Overman, Tetrahedron Lett., 1994,35, 3453. 81 C.Y. Hong, N. Kado, and L.E. Overman, J. Am. Chem. Soc., 1993, 115, 11 028. 82 K.A. Parker and D. Fokas, J. 0%. Chem., 1994,59, 3927. 83 G.C. Fu, S.T. Nguyen, and R.H. Grubbs, J. Am. Chem. Soc., 1993, 115, 9856. 84 0. Fujimura, G.C. Fu, and R.H. Grubbs, J. Org. Chem., 1994, 59,4029. 85 F.E. McDonald, C.B. Connolly, M.M. Gleason, T.B. Towne, and K.D. Treiber, J. 0%. Chern., 1993,58,6952. 206 Contemporary Organic Synthesis86 K. Miwa, T. Aoyama, and T. Shiori, Synlett, 1994, 461. 87 E.J. Corey and T.-P.Loh, Tetrahedron Lett., 1993,34, 88 R.L. Elliott, N.H. Nicholson, F.E. Peaker, A.K. Tdkie, 3979. J.W. Tyler, and J. White, J. OR. Chem., 1994, 59, 1606. 89 H. Primke, G.S. Sarin, S. Kohlstruk, G. Adiwidjaja, and A. de Meijere, Chem. Ber., 1994, 127, 1051. 90 T.A. Engler, B.W. Draney, and G.A. Gfesser, Tetrahedron Lett., 1994, 35, 1661. 91 J.A. Marshall and K.G. Pinney, J. Org. Chem., 1993, 58, 7180. 92 J.A. Marshall and B. Yu, J. Org. Chem., 1994, 59, 324. 93 G.G. Melikyan, 0. Vostrowsky, W. Bauer, H.J. Bestmann, M. Khan, K.M. Nicholas, J. Org. Chem., 1994, 59, 222. 94 J.M. Mellor and S. Mohammed, Tetrahedron, 1993, 49, 7547; hid., 7567. 95 J.M. Mellor and S. Mohammed, Tetrahedron, 1993, 49, 7557. 96 E.R. Civitello and H. Rapoport, J. Org Chem., 1994, 59, 3775.97 B.M. Trost and Z. Shi, J. Am. Chem. Soc., 1994, 116, 7459. 98 J.-P. Dulcere, N. Baret, and J. Rodriguez, J. Chem. Soc., Chem. Commun., 1994, 303. 99 N.J. Newcombe, F. Ya, R.J. Vijn, H. Hiemstra, and W.N. Speckamp, J. Chem. Soc., Chem. CommLin., 1994,767. 100 Z. Sheikh, R. Steel, A.S. Tasker, and A.P. Johnson, J. Chem. Soc., Chem. Commun., 1994, 763. 101 G. Jordine, S. Bick, U. Mdller, P. Welzel, B. Daucher, and G. Maas, Tetrahedron, 1994, 50, 139. 102 W.R. Roush and T.G. Marron, Tetrahedron Lett., 1993,34,542 1. 103 K.C. Nicolau, K.R. Reddy, G. Skokotas, F. Sato, X.- Y. Xiao, and C.K. Hwang, J. Am. Chem. Soc., 1993, 115,3558. 104 I. Kadota, Y. Matsukawa, and Y. Yamamoto, J. Chem. Soc. Chem. Cornmun., 1993, 1638. 105 M. Sasaki, T. Nonomura, M. Murata, and K. Tachibana, Tetrahedron Lett., 1994, 35, 5023. 106 C. Mukai, Y. Ikeda, Y. Sugimoto, and M. Hanaoka, Tetrahedron Lett., 1994, 35, 2 1 79. 107 J.M. Palazbn, M.A. Soler, M.A. Mamirez, and V.S. Martin, Tetrahedron Lett., 1993, 34, 5467. 108 N. Machinaga and C. Kibayashi, Tetrahedron Lett., 199534,5739. 109 J.S. Clark and G.A. Whitlock, Tetrahedron Lett., 1994, 35, 6381 * 110 J.S. Clark, S.A. Krowiak, and L. J. Street, Tetrahedron Lett., 1993, 34, 4385. 11 1 J.M. Takacs and S.V. Chandramouli, J. Org. Chem., 1993, 58, 73 15. 112 P.G. Andersson, Y.I.M. Nilsson, and J.-E. Bickvall, Tetrahedron, 1994, 50, 559. 113 K. Mikami and H. Kishino, J. Chem. Soc., Chem. Cornmun., 1993, 1843. 114 H.C. Brown and A.S. Phadke, Synktt, 1993, 927. 1 15 H. Waldmann, Synthesis, 1994, 535. 116 Q. Gao, K. Ishihara, T. Maruyama, M. Mouri, and H. Yamamoto, Tetrahedron, 1994, 50, 979. 117 Y. Motoyama and K. Mikami, J. Chem. Soc., Chem. Commun., 1994, 1563. 118 S. Koser, H.M.R. Hoffmann, and D.J. Williams, J. Org. Chem., 1993. 58, 6163. 119 L.F. Tietze, H. Geissler, J. Fennen, T. Brumby, S. Brand, and G. Schulz, J. Org. Chem., 1994, 59, 182. 120 E. Wada, H. Yasuoka, and S. Kanemasa, Chem. Lett., 1994, 145. 121 P. Pale, J. Bouquant, J. Chuche, P.A. Carrupt, and P. Vogel, Tetrahedron, 1994, 50, 8035. 122 P. Van de Weghe and J. Collin, Tetrahedron Lett., 1994,35, 2545. 123 P.A. Grieco and E.D. Moher, Tetrahedron Lett., 1993, 34, 5567. 124 A. Lubineau, J. Augi, E. Grand, and N. Lubin, Tetrahedron, 1994, 50, 10 265. 125 I. Paterson and J.D. Smith, Tetrahedron Lert., 1993, 34, 5351. 126 I. Paterson, J.D. Smith, R.A. Ward, and J.G. Cumming, J. Am. Chem. Soc., 1994, 116, 2615. 127 T. Patonay, G. Tbth, and W. Adam, Tetruhedron Lett., 1993, 34, 5055. 128 I.E. Mark6 and D.J. Bayston, Tetrahedron, 1994, 50, 7141. 129 J.P. Morken, M.T. Didiuk, M.S. Visser, and A.H. Hoveyda, J. Am. Chem. Soc., 1994, 116, 3123. 130 V.A. Boyd, B.E. Drake, and G.A. Sulikowski, J. Org. Chem., 1993, 58, 3191. 131 H.K. Jacobs and A.S. Gopalan, J. Org. Chem., 1994, 59, 2014. Burns: Saturated oxygen heterocycles 207