1,3-Cyclopentadiene, cycloaddition with 4+2 cycloadducts

Furanones are a class of chiral dienophiles very reactive in thermal cycloadditions. For example, (5R)-5-(/-menthyloxy)-2-(5H)-furanone (28) underwent Diels Alder reaction with cyclopentadiene (21) with complete re-face-selectivity (Equation 2.10), affording a cycloadduct which was used as a key intermediate in the synthesis of dehydro aspidospermidine [27]. 

C(sp2)=C(sp2) bond imparts properties which more closely resemble those of the central double bond in butatriene than of the one in a simple tetrasub-stituted ethylene [12]. For this reason, bicyclopropylidene (3) undergoes cycloadditions with 1,3-dienes, and these showed an interesting dependence on the structure of the diene. Whereas cyclopentadiene (6) gave the [4 + 2] cycloadduct 28 exclusively, 1,3-cyclohexadiene (26) and 1,3-butadiene (12) led to mixtures of the [4 + 2] and [2 + 2] cycloadducts, with the proportion of the [2 + 2] adduct increasing respectively [13] (Table 3). 

Various substituted unsaturated acylphosphonates participate in highly dias-tereoselective and enantioselective cycloadditions with vinyl ethers, Eqs. 177 and 178. It is intriguing to note that catalysts [(.V,.Y)-f-Bu-box]Cu (OTf)2 (269c) and [(.V,.S )-Ph-box]Cu (OTf>2 (269d) possessing the same sense of chirality afford opposite antipodes of the cycloadduct in comparable selectivities. Cyclopentadiene was found to react with acylphosphonates to give a mixture of the normal Diels-Alder adduct and the inverse electron demand hetero-Diels-Alder adduct (35 65), Eq. 179. This result may be contrasted with crotonylimide, which furnishes the normal demand Diels-Alder adduct exclusively. 

An extensive review of 4 - - 3-cycloaddition reactions has been presented. The 1,3-difluorooxyallyl intermediate obtained from l-bromo-l,3-difluoropropan-2-one undergoes 4 + 3-cycloaddition with cyclopentadiene and ftiran to give difluorobicyclo[3.2.1]octenones. The use of 4 + 3-cycloaddition reactions of cyclic oxyallyls in the synthesis of natural products has been extensively studied. The intramolecular 4 + 3-cycloaddition of allylic sulfones (111) possessing a diene in the side-chain in the presence of Lewis acids yield cycloadducts (112) in good to excellent yields (Scheme 43). ... 

A series of a,a-dimethoxysilyl enol ethers has been prepared and shown to undergo diastereoselective [4+3]-cycloaddition with furan and cyclopentadiene in the presence of catalytic amounts of trimethylsilyl triflate <99SL213>. Furo[3,4-d]oxazoles and furo[3,4-d]thiazo-les react with 13-dimethyloxyallyl to give [4+3]-cycloadducts. The ring opening reaction of these compounds with H2S04Mt20 yields armulated hydroxytropones <99H(51)1225>. 

The 4,5-double bond of 2(3//)-oxazolones participates in thermal [4 + 2] cycloaddition reactions. With dialkyl azodicarboxylates the addition occurs at 80 C to give the cycloadducts 430 (Scheme 97). With a chiral substituent attached to N(3), diastereoselectivities as high as 72% can be obtained. Cycloadditions with cyclopentadiene or benzofuran require higher temperatures and longer reaction times, but can yield highly efficient chiral oxazolidin-2-one auxiliaries. 

Alkenyl complexes can undergo cycloaddition with dienes. Thus the complex 6, prepared from vinyllithium, can be used as an alternative to the less reactive methyl acrylate. The cycloadducts can undergo various useful transformations (Scheme I). The reaction of 6 with cyclopentadiene gives a mixture of the endo- and exo-adducts in the ratio 94 6 in 78% yield. 

The pyridyl azirine 97 was prepared from mesitylsulfonyloxy oxime 96. This is one of the first examples of heteroaromatic substituted azirines reported. This azirine undergoes a Diels-Alder reaction with isobenzofuran to provide the rwn-cycloadduct 98 in 54% yield <2005S555>. In addition to isobenzofuran, this azirine undergoes cycloaddition with a number of different dienes, including cyclopentadiene (82%), 1-methoxy-butadiene (58%), and Danishefsky s diene (67%). 

R)- and (S)-f-Butyl-5-methylene-l,3-dioxolan-4-one, a Chiral a-Alkoxy Acrylate. It is also possible to introduce an ex-ocyclic double bond onto the dioxolanone ring, as in compounds (9)-(ll), derived from lactic and malic - acids. These a,3-unsaturated carbonyl derivatives are acceptors for radical additions and undergo cycloadditions with dienes and heterodienes. The Diels-Alder adduct (12) of ent-(9) with cyclopentadiene is formed with exo selectivity (96 4) and serves as aprecursor to norbomenone (13). Cycloadduct (14), obtained from methylenedioxolanone (9) and an open-chain triene, is also the result of an exo addition and is used in tetronolide synthesis. ... 

The [4+2] cycloadditions with anthracene [3] and 1,3-cyclopentadiene [3] proceed as expected surprisingly, dienes of lower activity, such as naphthalene [4] or fiirans [5], form Diels-Alder products likewise. The reactions of 1 with pentaflilvenes [6] and 1,3-cyclohexadiene [7] give stereoisomeric Z [2+2] cycloadducts and [4+2] products, whereas with butadienes [8] only [2+2] compounds are obtained. 

The method described here is the direct adaptation of the original procedure developed by the late Professor Hans Schmid- As summarized in Scheme 1, the Schmid reaction has been successfully applied to [4 + 3] cycloadditions with cyclopentadiene, spiro[2.4]hepta-4,6-diene, and N-Boc-pyrrole. Additional examples can be found in references 8 and 9. Use of functionalized six-membered oxyallyls and synthetic applications of the [4 + 3] cycloadducts have also been described.8... 

Like ketenes, allenes generally undergo [2 + 2] cycloadditions with alkenes affording methylene cyclobutanes . In reactions with 1,3-butadienes, both Diels-Alda- adducts and [2 -F 2] cycloadducts are formed. Cyclopentadiene, however, has been reported to react with several allenes to give exclusively Diels-Alder adducts. From the sevraal possible mechanisms by which [2 -F 2] cycloaddition reactions of allenes could occur,... 

The fumarate of ethyl f.S j-lactatc 38a exhibits very high diastereoselectivity in thermal cycloadditions with various dienes8. The cycloadduct 39, formed by the reaction of fumarate 38a with cyclopentadiene (2), is the starting material for the synthesis of ( + )-methyl epijasmonate9. 

Hexafluoroacetone alkoxycarbonylimines 29, exhibiting biphilic properties, act as 1,3-heterodienes or as dienophiles in [2 + 4] cycloadditions. With cyclopentadiene they react as dienophiles forming [2 + 4] cycloadducts, for example, 2-alkoxy-carbonyl-3,3-bis(trifluormethyl)-2-azabicyclo[2.2.1]hept-5-ene 30 (95IZV1809)... 

In the presence of a 1,3-diene this species produces [4 + 2] cycloadducts. The exact nature of this reactive intermediate has not yet been determined. It was found that a boron imide undergoes a Diels-Alder cycloaddition with cyclopentadiene under mild conditions [Eq. (25)].75... 

Reactions of methyl diselenobenzoate have been reported (Scheme 12) [17]. Cycloaddition of the diselenoate with cyclopentadiene gave the cycloadduct 95 as a stereoisomeric mixture in 67% yield. The reductive coupling of the same diselenoate mediated with copper yielded the alkene 96 with 39% yield. 

Koizumi and coworkers have developed a new enantiomerically pure a,p-unsaturated sulfoxide dienophile bearing the isoborneol group as a chiral auxiliary, dimethyl (f )-2-(10-isoborneolsulfinyl)maleate (214), which has been successfully employed as a chiral synthetic equivalent of dimethyl acetylenedicarboxylate [174], The dienophile (214) underwent cycloaddition with cyclopentadiene, in the presence of zinc chloride, with high stereo- and diastereoselectivity (92% single endo diastereoisomer, 6% single exo diastereoisomer) to yield the major cycloadduct (215), which was subsequently transformed into the half-ester (216), an intermediate in the syntheses of (-)-aristeromycin (199) and (-)-neplanocin A (200). Cycloadduct (215) has also recently been used for the synthesis of bicyclo[2.2.1]heptane lactone (217) [175,177], which itself is an intermediate in the synthesis of the iridoid (-)-boschnialactone [176] (218) (Scheme 5.69), and also in the formal synthesis of (-)-aristeromycin (199) and (-)-neplanocin (200) [177]. 

Carreno and colleagues [133,183] have synthesized enantiomerically pure (5)-2-p-tolylsulfinyl-l,4-benzoquinone (231), which, on cycloaddition with cyclopentadiene in the presence of a Lewis acid, gave cycloadducts (232a) and (232b) with good diastereofacial control (up to 82% de). The diastereoselectivity could be inverted by changing the Lewis acid used (e.g. chelation control in the case of Eu(fod)3 but not in the case of BFj-OEtj). In all cases, exclusive endo selectivity was observed (Scheme 5.74). 

Hetero-Diels-Alder Cycloaddition with Dienes. Under mild conditions, l,l -thiocarbonyldibenzotriazole readily reacts with cyclopentadiene to afford the hetero-Diels-Alder cycloadduct (4) (eq 2) in 98% yield. Analogous reaction with 2,3-dimethylbuta-diene, carried out under harsher conditions, was accompanied with elimination of a benzotriazole molecule to give benzotriazolyl-substituted thiopyran (5) (eq 3). ... 

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