Alder intramolecular allenic

A thermal intramolecular allene 1,2-diazine Diels-Alder reaction proceeded at 160 °C to afford indole derivatives [158],... 

An enantioselective synthesis of the Ziegler intermediate 107 of forskolin (108) has been achieved using an intramolecular allenic Diels-Alder reaction (Scheme 19.20) [24], Treatment of propargyl ether 104 with potassium tert-butoxide in tert-butanol affords 106, presumably through the intermediate allene 105. Compound 106 was obtained as a single stereoisomer. 

Lignans have been accessed using an intramolecular allenic Diels-Alder reaction (Scheme 19.21). Alkyne 109 was treated with potassium tert-butoxide at 60°C to afford a mixture of 112 and 113 via intermediates 110 and 111 [25]. Cydoadduct 112 could eventually be transferred to isomer 113 at room temperature by way of a second sigmatropic hydrogen shift. 

Substrates possessing an allene that participate in the Alder-ene reaction are less common, but a few examples are known. Malacria [11] and Livinghouse [12] have independently used cobalt to effect intramolecular allenic Alder-ene reactions but the scope of these reactions was not investigated. Sato has performed an allenic Alder-ene reaction to form five-membered rings, using stoichiometric amounts of titanium [13], and Trost has shown that 1,3-dienes can be prepared via an intermolecular Alder-ene reaction between allenes and enones using a ruthenium(II) catalyst [14]. 

The ether-tethered allenyne 248 undergoes a rhodium(l)-catalyzed intramolecular allenic Alder ene reaction to afford the ( )-3,6-dihydropyran 249 as the major product (Equation 111) <2002JA15186>. Likewise, ether tethered enynes can undergo rhodium(i)-catalyzed cycloisomerizations to afford 3,6-dihydropyrans <2005JA10180>. 

Kanematsu and coworkers developed the intramolecular allene+diene Diels-Alder cycloaddition into a new indole synthesis (Scheme 24, equations 1, 2) [118-121], The allene functionality in 67 was prepared by homologation (HCHO, CuBr, i-Pr NH). This cycloaddition strategy was successfully applied to syntheses of hippadine (equation 2) [119], and ( )- and (+)-d5 -trikentrin B [120, 121],... 

Alcaide, Aknendros and coworkers developed a combination of a 3,3-sigmatropic rearrangement of the methanesulfonate of an a-allenic alcohol to give a 1,3-bu-tadiene which is intercepted by a dienophile present in the molecule to undergo an intramolecular Diels-Alder reaction [83]. Thus, on treatment of 4-236 with CH3S02C1, the methanesulfonate was first formed as intermediate, and at higher temperature this underwent a transposition to give 4-237 (Scheme 4.51). This then led directly to the cycloadduct 4-238 via an exo transition state. 

Allenes as versatile synthons including Diels-Alder reactions and especially intramolecular cycloadditions of this type were reviewed by Aso and Kanematsu [338], In some cases of intramolecular Diels-Alder reactions of open-chain starting materials such as 340 [339], 342 [339] and similar acceptor-substituted allenes [156], the formation of two new six-membered rings seems to be favorable if possible (Scheme 7.48). The non-activated cumulated C=C bond of 340 takes part in the [4+ 2]-cycloaddition and hence the necessary reaction temperature is high. On the other hand, the progressive truncation of the tether and the electron deficiency of the allenic C=C bond involved give rise to a remarkable Diels-Alder reactivity of the sulfone 346 generated in situ from sulfoxide 345 [339]. 

Himbert and co-workers discovered the interesting intramolecular [4 + 2]-cycload-dition of allenecarboxanilides 353, which is possible even with monosubstituted benzenes (R H, Scheme 7.49) [25, 340]. During heating, partially an equilibrium between the allene 353 and the cycloadduct 354 is established. This Diels-Alder reaction can be applied to the corresponding N-(3-pyridyl) [335] or N-(l-naphthyl)... 

An intramolecular Diels-Alder reaction of allenic dienamide 181 provided the tet-rahydroindole ring system 182, which was oxidized with DDQ or Mn02 to give indole derivatives [147]. 

When propargylamine 183 was subjected to a homologative allenylation (Crabbe reaction) at 100 °C, the resulting allene underwent a spontaneous Diels-Alder reaction to give the adduct 184. This intramolecular cycloaddition-oxidation sequence provided a simple route to indole alkaloids such as hippadine and ds-trikentrin B [148]. 

Boger and Zhang s assembly of the intramolecular Diels-Alder adduct 97 is carried out by reacting 1,2-diazine 95 and allene 96 at high pressure for an extended time (Scheme 19.18) [22]. On heating to 120 °C, an intramolecular Diels-Alder reac-... 

In another approach to periplanone B by Cauwberghs and De Clercq, an intramolecular Diels-Alder reaction of furan-allene 122 afforded a mixture of two exo adducts 123 and 124 and an endo adduct (not pictured) in 90% yield and a 5 4 1 ratio (Scheme 19.23) [28], Refluxing the mixture in mesitylene (N2, 164 °C) afforded a 2 1 equilibrium mixture of 123-124 through a cydoreversion process. The Diels-Alder adduct 123 was converted to 125 via a series of synthetic manipulations, which constituted a formal total synthesis of periplanone B (126). 

Brummond [28] was the first to illustrate that cross-conjugated trienes could be obtained via an allenic Alder-ene reaction catalyzed by [Rh(CO)2Cl]2 (Eq. 14). Selective formation of the cross-conjugated triene was enabled by a selective cycloisomerization reaction occurring with the distal double bond of the aUene. Typically directing groups on the allene, differential substitution of the aUene termini, or intramolecularization are required for constitutional group selectivity. However, rhodium(f), unlike other transition metals examined, facihtated selective cyclization with the distal double bond of the allene in nearly aU the cases examined. 

The development of intramolecular Diels-Alder (IMDA) reactions for the synthesis of natural products (80CR63) and the facility with which substituted furans can be assembled have been reviewed 840R(32)1, 86CRV795, 87CSR187, 90SL186). Thus, IMDA product from the propargyl sulfone shown in Scheme 43 proceeds via the allene and was converted subsequently into the benzenoid sulfone under base catalysis (92CC735). 

Thiophenes can function either as a diene or as a dienophile in an intramolecular Diels-Alder reaction (90CC405). The 7V-(2-thienyl)allene carboxamide (182) on heating at 130°C leads to (183) by a [4 + 2] cycloaddition in which the thiophene functions as a 4ir component, followed by the usual extrusion of sulfur. 

As a first approach to the synthesis of nagilactone 296, a norditer-penoid isolated from Podocarpaceae, which inhibit the expansion and mitosis of plant cells, an intramolecular Diels-Alder reaction of allene 1,3-dicarboxylic acid esters was used. The cyclization of 297 afforded the 8-lactone 298, rather than the y-lactone 299 [85JCS(P1)747]. 

A tandem one-pot elimination-intramolecular Diels-Alder reaction occurs when the mesylate of 4-homoallylic azetidinone having a orc-alkene or alkyne substituent is heated in a sealed tube in the presence of an equimolecular quantity of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The method has been used to produce derivatives of oxace-pham. In a similar way, the 3,4-disubstituted azetidinone mesylate 473 afforded an 88% yield of 474. The method can be further elaborated through the introduction of a novel [3,3]-sigmatropic rearrangement of a-allenic mesylates thus, 475 yielded 476 on thermolysis C1999TL1015, 2000JOC3310, 2005EJ098>. 

The diyne 66 undergoes an intramolecular dehydro Diels-Alder reaction in toluene under reflux to afford naphtho[2,3-c]chromene derivatives in reasonable yield (Scheme 20). The reaction is presumed to proceed via a [4+2]-cycloaddition of the alkyne to the aryl alkyne group to form the cyclic allene intermediate 67, which then isomerizes to the aromatic product <2003SL1524>. 

S CONTENTS Introduction to the Series An Editor s Foreword, Albert Padwa. Preface, Dennis P. Curran. Intramolecular 1,3-Dipolar Cycloaddition Chemistry, Albert Padwa and Allen M. Schoffstall. Stereochemical and Synthetic Studies of the Intramolecular Diels-Alder Reaction, William R. Roush. Thermal Reaction of Cyclopropenone Ketals, Key Mechanistic Features, Scope and Application of the Cycloaddition Reactions of Cyclopropenone Ketals and p - Delocalized Singlet Vinyl Carbenes Three Carbon 1,1-/1,3-Dipoles, Dale L. Boger and Christine E. Brotherton-Pleiss. Index. 

Based upon the studies on the mechanism of the Cl sequence we rationalized that the elusive allenol intermediate 19 (Chap. 2.2) could participate in intramolecular trapping reactions as an allenyl ether. Furthermore, vinyl allenes are perfectly suited as dienes in Diels-Alder reactions. Considering both reactive functionalities, allenyl ethers and vinyl allenes, which are perfectly suited for domino processes, we designed an insertion sequence based upon cyclizing carbopalladation [76], where the vinyl aUene results from an isomerization of an alkynylation of a vinyl... 

Mechanistically, this new insertion-CI-Diels-Alder hetero domino sequence can be rationalized as follows (Scheme 64) After the oxidative addition of the aryl halide 115 or 118 to the in situ generated Pd(0) species the arylpalladium halide 120 intramolecularly coordinates and inserts into the tethered triple bond via a syn-carbopaUadation to furnish cyclized vinylpalladium species 121 with a p-acceptor substitution in a stereospecific fashion. Transmetallation of the in situ generated copper acetylide 122 gives rise to the diorganylpalladium complex 123 that readily undergoes a reductive elimination and liberates the electron poor vinylpropargylallyl ether 124. The triethylamine catalyzed propargyl-allene isomerization furnishes the... 

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