Aza-l,3-butadienes

Trifluoromethyl-l-oxa-2-aza-l,3-butadienes can be prepared in situ by 1,4-HBr elimination from the corresponding a-bromo oxime on treatment with base, and provide an interesting and versatile four-skeleton-atom building block [262] (equation 57). 

Lloveras et al. (2005) compared intervalence electron transfer in l,4-diferrocenyl-l,3-butadiene, [Fc—CH=CH—CH=CH—Fc] andin l,4-diferrocenyl-2-aza-l,3-butadiene, [Fc—CH=N— CH=CH—Fc]. Although intervalence electron transfer in [Fc—CH=CH—CH=CH—Fc] and [Fc—CH=CH—Fc] resemble each other, this process in [Fc—CH=N—CH=CH—Fc] is restricted to some degree. As the authors noted, the population of the state with the positive charge located on the iron attached to the 4-position of the 2-aza-l,3-butadiene bridge is dominant, with just a very small population (<0.1%) of the state with the charge on the other iron site (Lloveras et al. 2005). 

The crystal structures of 1-(4-methyl-l-pyrazolin-3-yl)-5,5-bis(trifluo-romethyl)-AM,2,3-triazoline, the 2 1 cycloadduct of diazomethane and 4-methyl-l,l-bis(trifluoromethyl)-2-aza-l,3-butadiene,359 387 1,4-... 

In a similar way to 1-oxa-l,3-butadienes, 2-aza-l,3-butadienes can also be prepared by condensation of an aldehyde such as 224 with anilines 225 to give, for example, novel azasteroids in a following cycloaddition reaction [60]. Thus, by condensa-... 

Lewis acid catalysis for aza Diels-Alder reactions of 2-aza-l,3-butadienes [254], In analogy to the hitherto discussed aza Diels-Alder reactions, evidence for a non-concerted mechanism of these transformations has emerged. Thus, Mellor et al. have found that under suitable conditions azaanthraquinone 3-34 does not only form the expected cycloadduct 3-37 upon treatment with a-methylstyrene and formaldehyde, but the tertiary alcohol 3-36 is also generated presumably via cation 3-35. Alcohol 3-36 is easily converted into the cycloadduct 3-37 and 3-35 is therefore supposed to act as intermediate in a non-concerted multistep sequence (Fig. 3-12) [255,256]. More recent studies on N-arylimines performed by Laschat et al. have corrobated the assumption that non-concerted processes represent a noteworthy mechanistic pathway in reactions of 2-aza-l,3-buta-dienes with suitable dienophiles [257]. 

An intramolecular aza Diels-Alder reaction of as well electronically neutral N-aryl imines useful for the synthesis of novel tetrahydropyridine derivatives has been introduced by our group [268]. The reactive intermediate 3-43 exhibiting the 2-aza-l,3-butadiene subunit was generated in situ from the aldehyde 3-41 and the amino isoxazole 3-42 and led directly to the diastereomerically pure cycloadduct 3-44 (Fig. 3-14). In contrast to the reactions studied by Barlu-enga, the 2-aza-1,3-butadiene acts as electron-deficient component in this case. 

Activation of 2-aza-l,3-butadienes for inverse electron demand aza Diels-Alder reactions can also be achieved by introducing electron-withdrawing substituents. Thus, Barluenga s group has developed 3,4-bismethoxycarbonyl-2-aza-1,3-butadienes which undergo smooth intramolecular cycloadditions upon heating [278]. 

Ghosez et al. could also achieve high asymmetric inductions by reacting electron-rich 2-aza-l,3-butadienes with a,/J-unsaturated chiral oxazolines [283]. Other applications of electron-rich 2-aza-l,3-butadienes in normal electron demand aza Diels-Alder reactions have been aimed at the preparation of natural cibrostatines [284] and azaanthraquinones [285]. 

A less usual type of 2-aza-l,3-butadienes is the class of C=C-conjugated carbodiimides like 3-59. They are readily available from iminophosphoranes and react smoothly with carbo- and hetero dienophiles to yield the desired heterocycles, e.g. 1,3-oxazine 3-60 (Fig. 3-18) [286-288]. 

The preparation of amphimedine 7-46 published by Echavarren and Stille [512] is a noteworthy application of 2-aza-1,3-butadienes in natural product synthesis since it is an interesting combination of hetero Diels-Alder methodology with a palladium catalysed cross coupling. Thus, dienophile 7-44 was formed by Stille coupling of the triflate 7-42 with the stannyl aniline 7-43. This qui-none then underwent cycloaddition to the 2-aza-l,3-butadiene 7-45 an acid catalysed hydrolysis of the cycloadduct 7-47 and subsequent N-methylation completed the synthesis of amphimedine 7-46 (Fig. 7-11). 

Aza-l,3-butadienes have also been reported to participate in IMDA reactions under thermal conditions. Dimethyl (E.Eyi - [2-(2-propenyloxy)phenyl]methylenamino -2-(trimethylsilyl) butenedioate gave a single cycloadduct on heating in toluene 69. 

The 2-aza-l, 3-butadiene (57), prepared by the action of t-butyldimethylsilyl triflate on diacetimide (MeCONHCOMe), undergoes Diels Alder cycloaddition with nitrosoarenes to yield 2-aryl-... 

Several examples of the intramolecular Diels-Alder reactions of unactivated 2-aza-l,3-butadienes have been detailed12,59-62 [e.g., Eq (30)].59,60... 

Only the E,3E stereoisomer of the 2-azadiene was found to be reactive under the reaction conditions. Consequently, each of the piperidine products was found to possess the cis 2-phenyl, 5-methyl relative stereochemistry. Moreover, the cycloaddition products derived from reactions of enol ethers possessed the all-cis 2-phenyl-4-alkoxy-5-methyl stereochemistry necessarily derived from exclusive endo cycloaddition. Dienophile geometry is maintained during the course of the [4 + 2] cycloaddition, and no products derived from a potential stepwise, addition-cyclization reaction were detected. Representative neutral and electron-deficient dienophiles failed to undergo cycloaddition. A related boron trifluoride etherate-catalyzed [4 + 2] cycloaddition of simple 2-aza-l,3-butadienes with carbonyl compounds provides 5,6-dihydro-2//-l,3-ox-azines and appears to proceed preferentially through an endo [4 + 2] transition state although evidence supporting a stepwise, addition-cycli-zation was occasionally detected.630... 

The reaction of phosphites with trifluoromethyl-substituted 2-aza-l,3-butadienes (19) gives the adducts (21), the structure and stereochemistry... 

Balsamini, C., Bedini, A., Galarini, R. et al. (1994) Reactions of 3-carbomethoxy-2-aza-l,3-butadiene derivatives with dienophiles. Tetrahedron, 50, 12375-12394. 

The anion (2) also reacts with ketones to give, after hydrolysis, alkylideneamino alcohols (5). On treatment with acid 5 is converted into -amino alcohols (6) on dehydration 2-aza-l, 3-butadienes (7) are formed. 

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