Dipolarophiles, defined

Inter [4 +2]/intra [3+2] This type of tandem reaction using nitroalkenes has been explored most extensively. Four subfamilies of tandem cycloaddition exist, which arise from the four different points of attachment of the dipolarophilic tether. They are defined as fused, spiro, and bridged modes, as depicted in Scheme 8.37.149... 

A systematic exploration of the intramolecular [4+2]/[3+2] cycloaddition cascade of 1,3,4-oxadiazoles was described. The studies permit the use of unsymmetrical dienophiles, dipolarophiles, and oxadiazoles as well as to control the cycloaddition regioselectivity and diastereoselectivity. The scope and utility of the reaction were defined <2006JA10589>. The tandem intramolecular [4+2]/[3+2] cycloaddition cascade reaction of 1,3,4-oxadiazole was applied to the syntheses of a series of natural products including a total synthesis of (-)- and ent-(+)-vindoline <2006JA10596>. 

Similarly, nitrile oxides react with methyl acrylate 2.42 to give the adduct 2.43 with the substituent on C-5 and terminal alkenes also react in this way to place the alkyl group on C-5. Many dipoles react well with electron-rich dipolarophiles, but not with electron-poor dipolarophiles. Other dipoles are the other way round. To make matters even more complex, the presence of substituents on the dipole can change these patterns and impart their own regioselectivity. Thus the carbonyl ylid reaction 2.45 has a well defined regiochemistry determined only by the substituents, since the core dipole is symmetrical. This reaction also illustrates the point that dipolarophiles do not have to be alkenes or alkynes—they can also have heteroatoms. 

Huisgen defined a 1,3-dipoleas a species that may be described (as in Equation 1) by zwitterionic octet structures 6a <- 6b, and which may undergo cycloaddition reactions of the type 3 + 2 -> 5 with suitable multiple bonds (dipolarophile d=e) to give a neutral five-membered ring 7. 

Alkenoylation of a camphor-based cyclic acylhydrazide leads to substrate-defined dipolarophiles (for nitrile oxides)." On temporary (in situ) derivatization with 75, enals are activated to undergo enantioselective cycloaddition with nitrones. ... 

Cycloadditions are stereospecific cis additions, as has been shown in several cases using geometric isomers as dipolarophiles . In addition to the rigid structure of norbornene, as well-defined approach is preferred, namely the one that gives an exo adduct, as is shown in (a) above for azides, but also occurs with C-phenyl-N-methyl-nitrone and for diphenylnitrilimine -. The alternative approach of the reactants is sterically hindered in the case of norbornene the steric course of reactions of norbornadiene can be different, as was found using phenyl azide as the 1,3-dipole . 

A large class of organic reactions that lead to the formation of five-membered heterocyclic molecules, have been designated as 1,3 dipolar cycloaddition reactions °. Huisgen has defined the 1,3 dipole to be a species which is represented by zwitterionic resonance structures (i.e. the standmd Lewis octet structures) and which undergoes 1,3 cycloadditions to a multiple bond system, the dipolarophile , as in structures (18) and (19). 

Nitronate Facial Selectivity in Intermolecular [3+2] Cycloadditions of Nitronates The majority of asymmetric dipolar cycloadditions of nitronates have been investigated in the context of the tandem [4 + 2]/[3 + 2] cycloadditions of nitroalkenes. With chiral, cyclic nitronates, the facial selectivity is primarily controlled by the steric environment that defines the diastereotopic faces of the nitronate. Nitronates obtained from [4 + 2] cycloadditions with vinyl ethers contain an acetal stereocenter that controls the approach of the dipolarophile. Nitronate 103 (Scheme 16.26) reacts with dimethyl maleate to produce predominantly nitroso acetal distal- QA through a distal approach of the dipolarophile [23]. The proximal approach provided the minor isomer with dr 7/l. Calculations suggest that the distal approach of the dipolarophile that leads directly to a chair-Uke conformation of the six-membered ring is slightly favored over the proximal approach [121]. 

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