Hetero-1 3-dienes cycloadditions

Yet another hetero-dien for cycloaddition reactions of glycals that had been used for the preparation of 2-deoxyglycosides is 2,4-dioxo-3-thioxo-pentane, generated in situ from 3-thiophthalimido-pentane-2,4-dion. The cycloaddition occurs with high... 

Af-Acyliminium ions are known to serve as electron-deficient 4n components and undergo [4+2] cycloaddition with alkenes and alkynes.15 The reaction has been utilized as a useftil method for the construction of heterocycles and acyclic amino alcohols. The reaction can be explained in terms of an inverse electron demand Diels-Alder type process that involves an electron-deficient hetero-diene with an electron-rich dienophile. Af-Acyliminium ions generated by the cation pool method were also found to undergo [4+2] cycloaddition reaction to give adduct 7 as shown in Scheme 7.16 The reaction with an aliphatic olefin seems to proceed by a concerted mechanism, whereas the reaction with styrene derivatives seems to proceed by a stepwise mechanism. In the latter case, significant amounts of polymeric products were obtained as byproducts. The formation of polymeric byproducts can be suppressed by micromixing. 

Related reactions Danishefsky s diene cycloaddition, Hetero Diels-Alder reaction ... 

Weinreb, S. M., Scola, P. M. N-acyl imines and related hetero dienes in [4+2]-cycloaddition reactions. Chem. Rev. 1989, 89,1525-1534. Marcelis, A. T. M., van der Plas, H. C. Diels-Alder reactions of diazines and pyridines. Trends Heterocycl. Chem. 1990, 1,111-123. 

The [4+2] cycloaddition is certainly one of the most important reactions in organic chemistry, and many books and reviews are dedicated to this topic [54]. In particular, Diels-Alder reaction of (hetero)dienes with (hetero)dienophiles is extensively used at the early stages of numerous syntheses to establish a structural scaffold which is then usually further elaborated toward more complex target structures. The [4+2] cycloaddition is usually an efficient method with predictably high regio and stereoselectivity as such it can enable the synthesis of highly functionalized polycyclic systems. 

Synthesis by Cycloaddition. Earlier reports have shown that acylnitroso-com-pounds add efficiently to dienes. Now a full paper describes the oxidation of hydroxamic acids to give acylnitroso-compounds which can act both as dienophiles or as hetero-dienes with respect to cyclopentadiene. Heating the bridged oxazine adducts causes partial rearrangement to dioxazines (Scheme 1). 

Suga S, Nagaki A, Tsutsui Y et al (2003) A-Acyliminium ion pool as hetero diene in [4-t-2] cycloaddition reaction. Org Lett 5 945-949... 

In the mid-1980s, Hoffman and co-workers described a simple synthesis of racemic mikanecic acid via in situ Diels-Alder dimerization of the diene generated from t-butyl 2-bromomethylbut-2-enoate. " The first example of a Diels-Alder reaction of a MBH adduct was the dimerization of 2-hydroxy-alkyle-nones" and the previously mentioned addition to anthracene. The appKcation of the MBH adducts as hetero dienes or precursors of dienes, and dienophiles for the Diels-Alder cycloaddition reactions was then initiated and expanded by the group of Hoffman. In a series of reports, Hofftnan and co-workers have described the in situ Diels-Alder dimerization of various dienes (157), generated via stereoselective dehydration with MsCl-DABCO-DMAP of the corresponding MBH adducts The elimination of water from MBH adducts always resulted... 

Malpass, 1977). Diels-Alder type [2 + 4]-cycloadditions are possible with certain hetero-"ene components (J.R. Malpass, 1977 S.F. Martin, 1980) or with highly reactive o-quinodimethanes as diene components (W. Oppoizer, I978A). 

Perfluoroalkyl groups adjacent to multiple bond systems lower the frontier molecular orbitals (FMOs) Therefore, cycloaddition reactions preferentially occur with electron-rich multiple-bond systems The preference of bis(trifluoromethyl)-substituted hetero-l,3-dienes for polar reacuons makes them excellent model compounds for developing new types of diene reactions deviating from the well documented Diels-Alder scheme (pathway 1) A systematic study of the reactions of diene (1 =2-3=4)-dienophile (5=6) combinations reveals new synthetic possibilities that have not yet been fully exploited as tools for preparative organic cherrustry (equation 25)... 

The chalcogene heterocycles have been used as stable precursors for sulfur-said selenium-cantaining hetero-l,3-dienes in cycloaddition reactions 3//-l,2,4-Thiaselenazoles are a convenient source of 4,4-bis(trifluoromethyl)-l-thia-3-aza-buta-1,3-dienes, and 3//-diselenazoles are a convenient source of 4,4-bis(trifluoromethyl)-l-selena-3-azabuta-l,3-dienes as well as bis(tnfluoro-methyl)-substrtuted nitrile ylides [137]... 

The above cycloaddition process consists of two separate [3-1-2] cycloaddition steps and represents a 1,3-2,4 addition of a multiple bond system to a hetero-1,3-diene [7S7]. The structure ot the azomethine imine intermediate has been proved unequivocally by X-ray analysis [195] Ethylene [194], acetylene [/iS2] . many alkyl- and aryl- as well sgemmal dialkyl- and diaryl-substituted alkenes [196,197, 198, 199], dienes [200], and alkynes [182, 201], certain cyclic alkenes [198, 199,... 

Cycloaddition reactions where bis(trifluoromethyl)-substituted hetero-1,3-dienes act as dienophiles have been descnbed for open-chain and cyclic dienes [115, 126, 127] The balance of the diene -dienophile activity of bis(tnfluoro-methyl)-substituted hetero-l,3-dienes can be influenced strongly by the substituents bonded to the inuno nitrogen atom For instance, A/-(arylsulfonyl) denvatives of tnfluoroacetaldimine and hexafluoroacetone imine do not act as dienes but exhibit only the dienophile reactivity of electron deficient imines [5 229, 234,235, 236 237] (equation 52)... 

Cycloaddition Reactions with Trifluoromethyl-Substituted Hetero-1,3-dienes... 

The reactions of bis(trifluoromethyl)-subsatuted hetero 1,3 dienes are predomi nantly LLJMO controlled processes [238] With polar or highly polarizable dieno philes, the tendency to undergo stepwise cycloaddition reactions is considerable Notably these hetero-1,3-dienes react with a,(l unsaturated hetero multiple bond systems across the hetero multiple bond exclusively [243, 246 248] (equation 53)... 

The classical Diels-Alder reaction is a cycloaddition between a conjugated diene and a second component, called dienophile, which has at least a n bond (Equation 1.1). When one or more heteroatoms are present in the diene and/or dienophile framework, the cycloaddition is called a hetero-Diels-Alder reaction. 

Lewis-acid-catalyzed asymmetric hetero-Diels-Alder cycloaddition of a 1-thiabuta-1,3-diene with chiral A/-acryloyl and A/-crotonyl oxazolidinone dienophile [105]... 

The first microwave-assisted hetero-Diels-Alder cycloaddition reaction was described by Diaz-Ortiz and co-workers in 1998 between 2-azadiene 198 and the same electron-poor dienophiles as for the preparation of pyrazolo[3,4-b]pyridines 200 (Scheme 72) [127]. These dienes reacted with... 

The hetero-Diels-Alder reaction can also employ dienes containing heteroatoms. Cycloaddition of substituted styrenes with di-(2-pyridyl)-1,2,4,5-tetrazine was investigated by Engberts (Eq. 12.56).127 Again, the rate of the reaction increased dramatically in water-rich media. Through kinetic studies, they showed that the solvent effects on the... 

Trapping reactions of benzoylmethyleneoxophosphorane 39 a with carbonyl compounds dispel any remaining doubts as to the existence of acylated phosphenes. Unlike the diphenylmethyleneoxophosphorane 9, whose P/C double bond participates in cycloadditions, compound 39 a acts as a hetero-1,3-diene and undergoes [4 + 2]-cycloaddition with aldehydes and ketones 10 I7,35> it may again be assumed that the reaction is a two-step process involving 55 as intermediate. 

While disilene 5 does not undergo Diels-Alder reactions with 1,3-dienes, the [4+2]-cycloaddition products are formed with heterodienes, e.g. 1,4-diazabutadienes [17] or a-ketoimines [19]. It can be deduced that the electron deficient properties of such dienes cause them to readily take part in hetero-Diels-Alder reactions, which have inverse electron demands. This is corroborated by theoretical calculations which predict an inverse electron demand of the Si-Si double bond it is strongly electron donating rather than electron accepting towards butadienes and other compounds [24,25]. 

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