1 - Aza-1,3 -butadienes

S+3C] Heterocyclisations have been successfully effected starting from 4-amino-l-azadiene derivatives. The cycloaddition of reactive 4-amino-1-aza-1,3-butadienes towards alkenylcarbene complexes goes to completion in THF at a temperature as low as -40 °C to produce substituted 4,5-dihydro-3H-azepines in 52-91% yield [115] (Scheme 66). Monitoring the reaction by NMR allowed various intermediates to be determined and the reaction course outlined in Scheme 66 to be established. This mechanism features the following points in the chemistry of Fischer carbene complexes (i) the reaction is initiated at -78 °C by nucleophilic 1,2-addition and (ii) the key step cyclisation is triggered by a [l,2]-W(CO)5 shift. 

Keywords inverse electron-demand Diels-Alder reactions, N-sulfonyl-1-aza-1,3-butadiene... 

Likewise, an efficient one-pot multicomponent synthesis of annelated 2-amino pyridines (e.g., 17) utilizing [4+2] cycloadditions has been described <06JOC3494>. The process involves the in situ generation of 1-aza-1,3-butadiene from a palladium-catalyzed coupling-isomerization reaction of aryl halides (e.g., 18) with propargyl V-tosylamines (e.g., 19). The resulting butadiene then undergoes cycloadditions with V.S -ketene acetals (e.g., 20) to form annelated pyridines (e.g., 17). 

Borohydrides normally do not attack carbon-carbon multiple bonds, and thus, a, 3-unsaturated imines (1-aza-1,3-butadienes) are reduced only at their C=N bond, under both thermal and microwave conditions. However, the corresponding (1-aza-1,3-butadiene)tricarbonyliron(O) complexes show a totally different reactivity under the same conditions, and a simultaneous reduction of both C=N and C=C takes place if microwave irradiation is applied25. When the reaction was performed with sodium borodeuterid, 1,2,3-trideutero, secondary amines were obtained. In contrast to their behaviour under microwave conditions, these complexes were totally inert to reduction by NaBH4 under thermal conditions (Scheme 4.7)25. 

Ab initio and density functional theoretical studies of the 4 + 2-cycloaddition of 2-azabutadiene with formaldehyde predict a concerted reaction that agrees well with experimental evidence.184 The azadiene A-phcnyl-l -aza-2-cyanobuta-l, 3-dicnc reacts with electron-rich, electron-poor, and neutral dipolarophiles under mild thermal conditions.185 5,6-Dihydro-4//-1,2-oxazines have been shown to be useftd as synthon equivalents of 2-cyano-l-azabuta-1,3-dienes.186 The intramolecular Diels-Alder reaction of 1-aza-1,3-butadienes (106) can be activated by a 2-cyano substituent (Scheme 37).187 Stereoselectivity in the hetero-Diels-Alder reactions of heterobutadienes, nitrosoalkenes, and heterodienophiles has been extensively reviewed.188 The azadiene l-(t-butyldimcthylsilyloxy)-l-azabuta-l, 3-diene (107) reacts with halobenzo-quinones, naphthoquinones, and /V-phcnylmalcimidc to yield low to good yields of various pyridine heterocycles (108) (Scheme 38).189 The 4 + 2-cycloaddition of homophthalic anhydride with /V-(cinnarnylidcnc)tritylamine produces the 3,4-adduct whereas with /V-(ci nnamyI i dcnc)bcnzyI idi nc the 1,2-adduct is produced.190... 

Diels-Alder reactions with electron-rich alkenes.1 Simple a,(i-unsaturated im-ines (1-aza-1,3-butadienes) do not undergo Diels-Alder reactions with dienophiles. In contrast, the N-phenylsulfonyl imines derived from an aldehyde or ketone undergo Diels-Alder reactions under forcing conditions with electron-rich dienophiles to... 

In the presence of boron trifluoride, organocuprates are added to 1-aza-1,3-butadiene derivatives to give 1,4 addition products in moderate to good yields after reaction with nucleophiles. When the nucleophile is 2-thienyl or 2-furyl, alkylation results in a simple addition on the imine double bond. The intermediate anion is also trapped by an electrophile.229... 

A recent study performed by Ghosez et al. deals with the use of unsaturated SAMP hydrazones as chiral 1-aza-1,3-butadienes for asymmetric cycloadditions [226]. In this investigation, the reaction of the chiral heterodiene 3-21 with N-methylmaleimide afforded the cycloadduct 3-22 in excellent induced diastereoselectivity (Fig. 3-7). Thus, the selectivities obtained are very promising, but the application of this method is restricted to highly reactive electron-deficient dienophiles. The complementary approach, an aza Diels-Alder reaction of an 1-aza-l,3-butadiene with a chiral dienophile.has been investigated by Waldner [227]. 

However, activation with suitable substituents is not the only method to make 1-aza-1,3-butadienes react in aza Diels-Alder reactions. Nevertheless, Lewis acid catalysis has not yielded good results in this area of hetero Diels-Alder chemistry. Interestingly, Lewis and Bronsted acids promote a [3 + 2] cycloaddition process instead of the aza Diels-Alder reaction upon addition of a,/ -unsatura-ted hydrazones to quinones [249],... 

Blechert et al. have opened a very elegant alternative to the classical hetero Diels-Alder methodology by generating the cationic radical 3-31 - which might be conceived as 1-aza-1,3-butadiene - from the 2-vinyl indole 3-30 by means of a single electron transfer process. In the presence of the tetrahydropyridine derivative 3-32 the radicalic intermediate was transformed into the tetracyclic compound 3-33 which contains the complete skeleton of the alkaloid gonio-mitine [250, 251]. The authors have postulated a stepwise mechanism for this [4+2] process, therefore it should be understood as a formal hetero Diels-Alder reaction (Fig. 3-11). 

Considerable acceleration of cycloadditions involving electron-rich 1-aza-1,3-butadienes by ultrasound irradiation has been observed recently [252,253]. Thus, the application of sonochemical techniques might emerge as helpful tool for Diels-Alder reactions of 1-aza-l, 3-butadienes. 

Like 1-aza-1,3-butadienes, 2-aza-1,3-butadienes may react as electron-rich or as electron-deficient component in aza Diels-Alder reactions upon appropriate substitution however, they differ in not necessarily needing an activation by appropriate substituents for sufficiently high reactivities. Another significant difference to the reactions of 1-aza-l,3-butadienes is the widespread use of... 

Reaction of the nitrone 4-184 with allenic esters 4-185 as described by Ishar and coworkers led to the benzo[fo]indolizines 4-186, together with small quantities of 4-187 (<5%) (Scheme 4.40) [63]. The first transformation is a 1,3-dipolar cydoaddi-tion this is followed by four further steps, including a [4+2] cycloaddition of an intermediate 1 -aza-1,3 -butadiene. 

Similaily, the noncomplementary addition of a C-2 electron-withdrawing substituent to the A/-phe-nylsulfonyl-l-aza-1,3-butadiene substantially lowers the 1-aza-1,3-butadiene Elumo (Table 10), accelerates its 4ir participation in a LUMOdiene-controlled [4 + 2] cycloaddition reaction, maintains the expected regioselectivity of the cycloaddition reaction, and potentially enhances the endo dia-steieoselectivity of the [4 + 2] cycloaddition reactions through the introduction of a substantial increase in the magnitude of the LUMO C-2 coefficient (Table 10 equation 8). ... 

A significant development in 1,2,3-oxadiazine chemistry is the preparation, in moderate yields (30-55%), of the 3,6-diaryl-2-arylsulfonyl-2,3-dihydro-6/f-derivatives (28) by a [4 -I- 2] regiospecific cycloaddition of 1,4-diaryl-1-aza-1,3-butadienes (26) with arenesulfonyl nitrosites (27 Ar = Ph or... 

Equally rare are 1,2,6-thiadiazine 1-oxides, however, they are available by cycloaddition of 1,4-diaryl-1-aza-1,3-butadienes with arylsulfinylamines (Section 6.16.9.2.2.1). 

---