Iminium hetero Diels-Alder reactions

One very fascinating domino reaction is the fivefold anionic/pericydic sequence developed by Heathcockand coworkers for the total synthesis of alkaloids of the Daphniphyllum family [351], of which one example was presented in the Introduction. Another example is the synthesis of secodaphniphylline (2-692) [352]. As depicted in Scheme 2.154, a twofold condensation of methylamine with the dialdehyde 2-686 led to the formation of the dihydropyridinium ion 2-687 which underwent an intramolecular hetero- Diels-Alder reaction to give the unsaturated iminium ion 2-688. This cydized, providing carbocation 2-689. Subsequent 1,5-hydride shift afforded the iminium ion 2-690 which, upon aqueous work-up, is hydrolyzed to give the final product 2-691 in a remarkable yield of about 75 %. In a similar way, dihydrosqualene dialdehyde was transformed into the corresponding polycyclic compound [353]. 

The starting material was prepared with the modification on the epibatidine bicychc ring system by repositioning the nitrogen atom to a methylene group. We carried out the Hetero-Diels Alder reaction of cyclopentadiene and iminium ion generated from ammonium chloride and formaldehyde in the aqueous medium and protected resulted unstable secondary amine with benzoyl chloride to provide (3) in good yields [5] (Scheme 38.1). 

Aqueous hetero Diels-Alder reaction was first described by Grieco, who reported the use of water as solvent for cyclocondensations of iminium salts (Larsen and Grieco, 1985). Known as being a very energy demanding reaction, the retro Diels-Alder process is usually not considered as a competitive pathway in most Diels-Alder... 

Dilatometry has been applied, for example, in the study of polymerisation or depolymerisation reactions that can lead, respectively, to a decrease or increase in volume [59]. Recently, Mayr and colleagues used this technique to study the kinetics of hetero Diels-Alder reactions, namely [2+ + 4] cycloadditions of iminium ions with 1,3-dienes [60]. 

Catalysts (25) are the Lewis acid-Lewis base bifunctional catalysts in which Lewis acid-Al(III) moiety activates acyl iminium ion and the Lewis base (oxygen of phosphine oxide) does TMSCN, simultaneously (Scheme 5.7). Halogen atoms at the 6-position enhanced both yields and enantioselectivity in Reissert-type cyanation of the imino part of 26. However, the order for the activation is not parallel to the electronegativity of the halogen atoms and, moreover, the strong electron-withdrawing trifluoromethyl group provided unexpectedly the worst result for the activation [13]. It is not simple to explain this phenomenon only in terms of the increased Lewis acidity of the metal center. Trifluoromethylated BINOL-zirconium catalysts (28) for asymmetric hetero Diels-Alder reaction (Scheme 5.8) [14], trifluoromethylated arylphosphine-palladium catalyst (32) for asymmetric hydrosilylation (Scheme 5.9) [15], and fluorinated BINOL-zinc catalyst (35) for asymmetric phenylation (Scheme 5.10) [16] are known. 

A number of examples have been reported of the asymmetric hetero Diels-Alder reaction of heterodienes or heterodienophiles such as imines, nitroso or carbonyl compounds.The chiral auxiliary is commonly attached to the nitrogen atom of the imine or nitroso compound, or a chiral ester or amide substituent may provide the necessary asymmetric induction. As an example, the a-cWoronitroso dienophile 132, bearing a sugar-derived auxiliary, has been found to be effective for the formation of cyclic hydroxylamines with high optical purity (3.95). The initial cycloadduct breaks down readily (see Scheme 3.32), via an iminium ion with subsequent methanolysis to release the chiral auxiliary and the product 133. 

From the numerous ir-systems investigated, nitrogen-containing dienophiles are the most typical carbonyl derivatives for hetero Diels-Alder reactions. Simple imines, however, are quite unreactive and require highly reactive dienes as counterparts. - In contrast, electron-deficient species, such as iminium salts (134 Scheme 63) or N-acylimines (137 Scheme 64), do undergo [4 -t- 2] cycloadditions with normal nonactivated dienes. Thus, the intramolecular Diels-Alder reaction of the iminium species (134), created in situ from the aldehyde (133) and ammonia, gives the octahydroquinoline (135), which can be hydrogenated to afford the 8a-epimer of pumiliotoxin C (Scheme 63). ... 

Recently, Jacobsen described a novel strategy for inducing enantioselectivity in reactions of protio-iminium ions, wherein a chiral catalyst interacts with the highly active intermediate through a network of non-covalent interactions (as shown in transition state Q) [69]. Accordingly, a highly efficient and enantioselective aza-hetero-Diels-Alder reaction between N-aryl imines 152 and enamide 153 or ene-carbamate 154 has been achieved with the use of the combination of the bifunctional sulfinamido urea derivative 155 and ortho-nitrobenzensulfonic acid (156) (Scheme 38.46). The 2 1 ratio of 155 and 156 was essential to ensure the complete suppression of the racemic pathway catalyzed by 156 [69]. 

Diels-Alder Reactions The organocatalytic Diels-Alder reaction of a,P-unsaturated carbonyl compounds can be performed either via iminium (see Section 11.3) or enamine catalysis. The first highly selective enamine-promoted cycloaddition reaction was reported by Jprgensen and coworkers, who developed an amine-catalyzed inverse-electron-demand hetero-Diels-Alder (HDA) reaction (Scheme ll.lOa). ... 

In this transformation two new C-C-rr-bonds are formed from three different components. The enantioselectivity of this reaction is generally low (< 5%). With cyclic ketones the corresponding products were obtained as single diastereomers. It is proposed that this reaction involves a Knoevenagel-hetero-Diels-Alder sequence where proline utilizes both iminium and enamine catalysis (Scheme 9.20). 

Heterocyclic iminium salts, oxidative transformation, 41, 275 Heterocyclic mesomeric betaines and analogs in natural product chemistry, 85, 67 Heterocyclic oligomers, 15, 1 Heterocyclic products, natural, synthesis of by hetero Diels-Alder cycloaddition reactions, 42, 245... 

Iminium ions as dienophiles in aza-Diels—Alder reactions 12CEJ12554. Industrial applications of the Diels—Alder reaction including hetero-Diels—Alder reacrtion 13AG(E)3822. 

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