Hetero-ene

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). 

Two examples of [4 + 2] cycloadditions of allylidene cyclopropanes with hetero-enes have been previously reported in Krief s review [31]. Only a few other examples have been studied more recently. 

The ene reaction, an electronic relative of the Diels-Alder cycloaddition, is a six-electron process involving the reaction of the n and allylic reactions these reactions are reviewed in detail (for reviews of the Alder-ene reaction and related chemistry, see Refs 1,1a, and lb). Recent developments in the area of hetero-ene chemistry (X1 = H, X2 = N,0) are also surveyed. 

Like so many other reactions, the ene reaction has been given new life by metal catalysis. The use of metals ranges from common Lewis acids, which simply lower the barrier of activation of the hetero-ene reactions to transition metal catalysts which are directly involved in the bond-breaking and -forming events, rendering reactions formal ene processes. This review is meant to serve as a guide to the vast amount of data that have accumulated in this area over the past decade (1994-2004). If a particular subject has been reviewed recently, the citation is provided and only work done since the time of that review is included here. Finally, the examples included within are meant to capture the essence of the field, the scope, limitations, and synthetic utility therefore, this review is not exhaustive. 

The robustness and versatility of the Alder-ene and hetero-ene reactions are evidenced by their wide-ranging application to the synthesis of biologically relevant substrates over the past decade. In the section below, we have highlighted a few of these examples. 

Deprotonation of one of the Me groups adjacent to S gives an ylide which can undergo a retro-hetero-ene reaction to give the observed products. 

If (CD3)2SO (deuterated DMSO) is used for the Swem reaction, the E2 mechanism predicts that the sulfide product should be (CD3)2S the retro-hetero-ene mechanism predicts that it should be (CD3)S(CHD2). Guess which product is actually found ... 

The second product must incorporate two equivalents of the enol ether. We form C3-C5, C5-C4, and C5-S1 bonds, and we transfer a H from SI to C4. A hetero-ene reaction forms the C3-C5 bond and transfers the H. As for the other two bonds, since SI and C5 are at the ends of a four-atom unit, we might expect a Diels-Alder reaction. We can get to the requisite diene by eliminating the elements of BuOH by an Elcb mechanism. The hetero-Diels-Alder reaction gives the product with ertdo stereoselectivity and the expected regioselectivity. 

The conversion of 5 to 6 is a Swern oxidation. The O of DMSO is nucleophilic, and it reacts with oxalyl chloride. Cl- then comes back and displaces O from S to give a S electrophile. The OH of 5 is then deprotonated, whereupon it attacks S, displacing CL. Then deprotonation of a Me group and a retro-hetero-ene reaction occur to give the ketone. 

A new approach to spirolactams involving the thermal reaction of A-unsaturated alkyl /1-carboxamidoenamines in which the enamine is the hetero-ene component has been reported.326 A-Alkylnitrilium salts have been shown to undergo ene reactions with electron-rich alkenes to afford either 2-azoniaallene salts (where the nitrilium salt acts... 

Depending on the type of iron catalyst, the reaction seems to take different mechanistic pathways. According to Johannsen and Jorgensen s results, the catalytic cycle starts with the formation of nitrosobenzene 32 either by disproportionation of hydroxylamine 29a to 32 and aniline in the presence of oxo iron(IV) phthalocyanine (PcFe4+=0) or by oxidation of 29a [131]. The second step, a hetero-ene reaction between the alkene 1 and nitrosobenzene 32, yields the allylic hydroxylamine 33, which is subsequently reduced by iron(II) phthalocyanine to afford the desired allylic amine 30 with regeneration of oxo iron(IV) phthalocyanine (Scheme 3.36). That means the nitrogen transfer proceeds as an off-metal reaction. The other byproduct, azoxybenzene, is probably formed by reaction of 29a with nitrosobenzene 32. 

Aminoindanol-derived Schiff bases were developed as tridentate ligands for the chromium-catalyzed hetero Diels-Alder reaction between weakly nucleophilic dienes and unactivated aldehydes.24 The generality of the utility of these Schiff bases, readily obtained by condensation of 1 with the corresponding aldehyde, was later demonstrated in the hetero Diels-Alder reaction between Danishefsky s diene and chiral aldehydes,25 in the inverse electron-demand hetero Diels-Alder reaction of a,P-unsaturated aldehydes with alkyl vinyl ethers,26 and in hetero-ene reactions.27... 

Reaction of hexacarbonyldicobalt complexes of ene-ynes or hetero-ene-ynes with (biscyclooctene)(tricarbonyl)iron results in formation of [FeCo2 (p.-alkyne)(CO)9] (Scheme 15).142 In both cases the free double bond in the vicinity of the Co2C2 unit facilitates the incorporation of the incoming Fe(CO)3 fragment. 

The Lewis acid salen complex 4 (Scheme 10.7) readily catalyzes the conversion of (-i-)-citronellal to 1-isopulegol via an intramolecular hetero-ene reaction. It is noteworthy to mention that this reaction is of importance in the industrial production of... 

J-menthol. In addition, this complex also catalyzes the intermolectdar hetero-ene reaction between activated enophdes and olefins to give homoallylic alcohols via a stepwise process (Scheme 10.27) [53],... 

Although this last step is reasonable, it is not the way that the elimination actually takes place. In the currently accepted mechanism, the CH3 group is deprotonated to give a sulfur ylide, and a retro-hetero-ene reaction ensues. Retro-hetero-ene reactions are discussed in Chapter 4. 

The ene reaction also occurs when heteroatoms replace C in either the ene or the enophile. The following hetero-ene reaction requires a much lower activation energy than normal because of the driving force of formation of the aromatic indole ring and because of the instability of ethyl glyoxylate, which has adjacent carbonyl groups. 

Problem 4.20. The final step of the Swem oxidation involves elimination of MctS and H+ from a sulfonio ether. An E2 mechanism for this elimination is reasonable, but a retro-hetero-ene mechanism is actually operative. Draw the... 

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