Applications of the intramolecular Diels-Alder reaction to the formation of strained molecules. Synthesis of bridgehead alkenes

Shea, Kenneth J.; Wise, Sean; Burke, L. D.; Davis, Peter D.; Gilman, Jeffrey W.; GREELEY, A. C.

doi:10.1021/ja00385a027

Cited by 74 publications

(19 citation statements)

References 2 publications

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“…in the presence of Et,N revealed the presence of a small amount (< 10%) of the same two products observed above and indicated that TIPSOTf alone could promote the IMDA r e a~t i o n .~ Reaction of the mixture of 22d23a with TIPSOTf (2 equiv.) for 2 h followed by HF work-up gave 45 (44%) and 46 (42%) in good yield (based on 23a) in addition to recovered 22a (8 (27). However, Diels-Alder adducts could, in principle, be derived from 26a by initial rearrangement to 27a by a [1,5] ( 5 3 , 46 (43) 45 (44), 46 (42) 45 (38), 46 (34) Nonec None 49 (40), 50 (15) 49 (37).…”

Section: H-thiopyrans Had Established the 4-(triisopropylsilyl)oxymentioning

confidence: 98%

“…50 (14) 49 (48), 50 (19) 47 (70). 48 (10) 45 (44), 46 (43) 45 (34), 46 (27) Disappointingly, the expected IMDA adducts were not detected after heating C6D6 solutions of 1.3: 1 mixtures of 26bl 27b or 28b129b at 140-1 80°C over several days. Only the oxidation products 30b and 31b were isolated after the usual HF work-up.…”

Section: H-thiopyrans Had Established the 4-(triisopropylsilyl)oxymentioning

confidence: 99%

“…The failure of 4 0 and 4 2 to produce adducts (cf. 27,29) is presumably the result of the unfavorable regiochemistry enforced by the short tether, thereby increasing the activation energy for IMDA reaction and precluding cycloaddition in favor of other pathways. T o examine the possibility of effecting IMDA reaction of a C-6 tethered substrate that would allow favorable regiochemistry, compounds 6 2 and 6 3 were prepared according to Scheme 6.…”

Section: H-thiopyrans Had Established the 4-(triisopropylsilyl)oxymentioning

confidence: 99%

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Intramolecular Diels–Alder reactions of 2H-thiopyran dienes

Ward¹,

Nixey²,

Gai³

et al. 1996

Can. J. Chem.

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Abstract:A systematic survey of IMDA reactions of 4-[tris(2-methylethyl)silyl]oxy-2H-thiopyran derivatives with potential dienophiles tethered at the C-2, C-3, C-5, and C-6 positions is presented. Cycloaddition was not observed with a C3 or C4 tether and an unactivated terminal olefin as dienophile. IMDA adducts could be obtained when dienophiles activated by a carbomethoxy group were employed. Compounds having the activated dienophile attached via a C3 tether to C-2 of the 2H-thiopyran gave adducts with high stereoselectivity. Substrates having the dienophile attached to C-3 with a C j or C, tether cyclized readily. With an (E)-enoate as the dienophile, the stereoselectivity was poor (endo:exo = 1.1-2.5: 1) and essentially independent of reaction conditions (i.e., thermal vs. Lewis acid mediated). With the (a-enoate, a 7: 1 mixture of enclo:e.ro IMDA adducts was obtained under thermal conditions; with Lewis acid catalysis, isomerization of the dienophile was competitive with cycloaddition. Type I1 IMDA adducts were not observed with C-5 tethered substrates. Compounds having the dienophile attached to C-6 via a C j or a five-atom tether also failed to give IMDA adducts. No evidence for isomerization of the 2H-thiopyran dienes by [1,5] sigmatropic rearrangement was observed. The etzclo adducts from IMDA reactions of the C-3 tethered substrates can be desulfurized to obtain synthetically useful trarzs-fused hydrindans and decalins with angular methyl groups.Key words: intramolecular Diels-Alder, 2H-thiopyran, cis-substituted 1,3-diene surrogate, trntls-octahydro-3a-methyl-IHindene derivatives, trcirls-decahydro-4a-methylnapthalene derivatives.RCsumC : On prCsente une Ctude des rCactions DAIM des dCrivCs du 4-[tris(2-mCthylCthyl)silyl]oxy-2H-thiopyrane avec des diknophiles potentiels attach& en positions C-2, C-3, C-5 et C-6. On n'observe pas de cycloaddition avec des laisses de 3 ou 4 atomes de carbone et une olCfine terminale dCsactivCe comme dienophile. Les adduits DAIM peuvent Ctre obtenus lorsque l'on utilise des dienophiles activCs par un groupe carbomCthoxy. Les composCs ayant le diCnophile attach6 par une laisse de 3 carbones attachCe au carbone en position 2 du 2H-thiopyrane donne des adduits avec une trks grande stCrCosClectivitC. Les substrats ayant un diCnophile attach6 en C-3 avec une laisse de 3 ou 4 atomes de carbone se cyclisent rapidement. Si on utilise un (E)-Cnoate conime diCnophile on obtient une faible stCrCosClectivit6 (et~clo : exo = 1,l-2,5 : I ) qui est independante des conditions de rCaction (c.-i-d., thermique versus une catalyse par acide de Lewis). Avec un (a-Cnoate on obtient un mklange d'adduits DAIM etlclo : eso dans la proportion de 7 : 1 par voie thermique tandis que la catalyse par un acide de Lewis conduit une compCtition entre I'isomCrisation du diCnophile et la cycloaddition. On n'a pas observe d'adduits DAIM de type I1 avec les substrats liCs en C-5. Les composCs ayant un diCnophile attach6 en C-6 via une liesse de 3 ou de 5 atomes de carbone ne donnent pas non plus d'adduits ...

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Section: H-thiopyrans Had Established the 4-(triisopropylsilyl)oxymentioning

confidence: 98%

Section: H-thiopyrans Had Established the 4-(triisopropylsilyl)oxymentioning

confidence: 99%

Section: H-thiopyrans Had Established the 4-(triisopropylsilyl)oxymentioning

confidence: 99%

See 1 more Smart Citation

Intramolecular Diels–Alder reactions of 2H-thiopyran dienes

Ward¹,

Nixey²,

Gai³

et al. 1996

Can. J. Chem.

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“…Previous work on related systems (Shea et al, 1982;Shea, Lease & Ziller, 1990;Shea, Staab & Zandi, 1991) indicated that the length of the 'tether' between the 2-position of the diene and the dienophile influences the regioselectivity, with a fiveatom tether preferentially giving the 'meta" adduct (Shea et al, 1991). Compound (1)has a four-atom methine and methylene resonances.…”

Section: (1)mentioning

confidence: 99%

Structure of the epoxide of a tricyclic lactone

Mague¹,

Ensley²

1993

Acta Crystallogr C

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“…The cycloadditions of diesters 6 and 13 were also performed in toluene and resulted in 89% and 92% yields, respectively. The ramp time for the toluene reactions is approximately 25 minutes, however, the yields are excellent as compared to the cycloaddition of trienes 16 5 and 17 3 in o -xylene. This discrepancy may be attributed to trienes 6 - 14 possessing a less polarized dienonphile reducing any nucleophilic attack or polymerization.…”

mentioning

confidence: 99%

Microwave Assisted Synthesis of Bridgehead Alkenes

2011

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A new, concise method to synthesize triene precursors for the type 2 intramolecular Diels-Alder reaction has been developed. Microwave irradiation of the trienes provides a convenient method for the synthesis of bridgehead alkenes. Higher yields, shorter reaction times and lower reaction temperatures provide a general and efficient route to this interesting class of molecules.The type 2 intramolecular Diels-Alder (IMDA) reaction is a powerful tool for the construction of polycyclic compounds containing bridgehead alkenes. i Highly strained bicyclo[n.3.1],ii-11 five-seven fused, 12 azobicyclo[n.3.1], 1iii and caprolactam ring systems 1iv can all be synthesized with high regio-and stereo-selectivity utilizing this reaction. Application as a key carbon-carbon bond forming step in the syntheses of complex molecules aptly displays the synthetic significance of the reaction. 1v,16 The type 2 IMDA reaction has an elevated activation free energy as compared to the type 1 IMDA variant due in part to the formation of a strained bridgehead alkene and the cumulative non-bonding interactions that develop in the transition state leading to the bridged bicyclic product. Experimental values of the activation free energy (ΔG ‡ ) for the reaction range from approximately 37-41 kcal/mol (210 °C). 8 This energy barrier is overcome with either elevated reaction temperatures for extended periods of time3 , 4 or by the use of Lewis acid catalysis.6 In a complex molecule setting, Lewis acid activation is often prohibited due to the presence of more sensitive functional groups. 16 Solution phase thermolysis is then necessary to induce cycloaddition of highly functionalized trienes, however, this often requires temperatures in excess of 200 °C with reaction times of several hours. The yields of these reactions are often compromised by competing decomposition of the diene under these harsh and prolonged conditions. Alternately, use of microwave radiation has been known to decrease reaction times and lower temperatures for reactions carried out under thermal conditions. 17,18 A microwave reactor also provides a more convenient, safer method for heating reactions to the temperatures necessary for the type 2 IMDA reaction to occur. We thus set out to develop a straightforward method using kjshea@uci.edu . Supporting Information Available Experimental procedures, spectroscopic data ( 1 H NMR, 13 C NMR, IR, HR-MS) for all new compounds. This material is available free of charge via the Internet at http://pubs.acs.org. A succinct method to synthesize these triene substrates was designed (Scheme 1). Utilizing enyne metathesis, alkynes can be viewed as protected dienes. Under 300 psi of ethylene, iodoalkyne 1 19 was converted to diene 2. Iododiene 2 was then coupled with acid chloride 3 or 4 to furnish trienes 5 or 6, respectively. Similarly diester 13 can be synthesized from pentynol 7 (Scheme 2). Silyl protection of the alcohol followed by alkyne metathesis gave diene 9. After deprotection of the silyl group and condensation of the r...

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Applications of the intramolecular Diels-Alder reaction to the formation of strained molecules. Synthesis of bridgehead alkenes

Cited by 74 publications

References 2 publications

Intramolecular Diels–Alder reactions of 2H-thiopyran dienes

Intramolecular Diels–Alder reactions of 2H-thiopyran dienes

Structure of the epoxide of a tricyclic lactone

Microwave Assisted Synthesis of Bridgehead Alkenes

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