Aza-cycloaddition

Alcaide B, Almendros P, Alonso JM, Redondo MC (2003) Asymmetric synthesis of unusual fused tricyclic P-lactam structures via aza-cycloadditions/ring closing metathesis. J Org Chem 68 1426-1432, and references therein... 

Aza-cycloaddition reactions, especially of the [4+2]- type, continue to be of interest for the synthesis of piperidines in various oxidation states. Danishevsky s diene 164 and N-... 

Mechanistically, as illustrated in Scheme 12.66, this intermolecular process (279 -I- 280 282) involves a tandem Knoevenagel condensation/6jt-electron electrocyclic ring-closure of 1-azatrienes 281 [126,127] to give fused heterocyclic system 282 [128,129]. The regiochemical control [5], head-to-head versus head-to-tail (i.e., the Hickmott-Stille s aza-cycloaddition) [130], is the challenge in this and other related cycloadditions, which can be unpredictable and leads to complex mixtures [4-6,131]. However, in our cycloadditions, the use of a, 3-unsaturated iminium salts has led to head-... 

SCHEME 12.67 Aza-cycloadditions with chiral vinylogous amides. 

SCHEME 12.68 Aza-cycloadditions with chiral imimum ions. 

On the other hand, when we investigated the enantiose-lective aza-[3- -3] annulation of pyrroUdine-based exocyclic vinylogous amides and urethanes 297, the similar chiral amine salts catalysts 299 or 300 still work very well at 40 mol% catalyst loading, afforded the indolizidines products 301 with up to 70% ee. Specially, this asymmetric aza-cycloaddition is an unexpected regiochemical reversal... 

Despite such potential significance, the synthetic scope of this type of aza-[3- -3] cycloaddition has been insufficiently explored until the last 15 years. An impressive array of aza-[3+3] cycloadditions, including earlier works, had been accounted for in a collection of reviews in 2005 [4—8], Summarized in Figure 12.2 are selected examples of total syntheses and methodological developments reported recently [145], and notably, these examples also include elegant aza-[3+3] concepts that are not directly related to our aza-cycloaddition. In our own efforts, we have been... 

Tangutorine To prepare aza-cycloaddition substrate 378, tryptamine 371 was diprotected and brominated so that an ensuing Heck coupling would provide ester 377 in 82% yield (Scheme 12.93). Further synthetic manipulations, including condensation with 1,3-cyclohexanedione 106,... 

The chalcogene heterocycles have been used as stable precursors for sulfur-said selenium-cantaining hetero-l,3-dienes in cycloaddition reactions 3//-l,2,4-Thiaselenazoles are a convenient source of 4,4-bis(trifluoromethyl)-l-thia-3-aza-buta-1,3-dienes, and 3//-diselenazoles are a convenient source of 4,4-bis(trifluoromethyl)-l-selena-3-azabuta-l,3-dienes as well as bis(tnfluoro-methyl)-substrtuted nitrile ylides [137]... 

One of the features of Diels-Alder reactions with most alkyl and aryl nitriles that has made them rather unattractive as dienophiles is the requirement of very high reaction temperatures Again, only when electron-withdrawing substituents are directly bonded to the nitnle function do [4+2] cycloaddition reactions occur at reasonably low temperatures [ 48, 231, 232] A high yield [4+2] cycloaddition was observed on reaction of 4,4-bis(trifluoromethyl) 1 thia-3-aza-l,3-butadienes with trifluoroacetonitrile at 150 °C [225]... 

Covalent fluondes of group 3 and group 5 elements (boron, tin, phosphorus, antimony, etc ) are widely used m organic synthesis as strong Lewis acids Boron trifluoride etherate is one of the most common reagents used to catalyze many organic reactions. A representative example is its recent application as a catalyst in the cycloadditions of 2-aza-l,3-dienes with different dienophiles [14] Boron trifluoride etherate and other fluonnated Lewis acids are effective activators of the... 

The tricyclic 1,3-diazepines 3 are formed by the action of two molar equivalents of aromatic isocyanates on the bis(imino-A5-phosphane) 1 in toluene at 20 C for 16 hours in a tandem aza-Wittig [2 t 2]-cycloaddition reaction . No further details were reported.167... 

Ahern and Gokel (1979) briefly mention that (jE -arenediazocyanides also react with a variety of dienes (cyclopentadiene, cyclohexadiene, butadiene, ( )-piperylene, etc.) in a [4+ 2]-cycloaddition reaction with formation of tetrahydropyridazines (Scheme 6-31). Here the two azo nitrogen atoms of the diazocyanide react as a dieneophile in a bis-aza Diels-Alder reaction. 

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. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

The cycloaddition of chiral, racemic and non-racemic alkoxybutadienes 109 with phenyltriazolinedione led to aza compounds [110] in high yield, with good facial selectivity (diastereomeric excess 87-92%) (Equation 2.31). The cycloadditions of the same dienes with N-phenylmaleimide require Lewis acid catalysis. 

The aqueous aza-Diels-Alder reaction of an aldehyde and an amine hydrochloride with a diene is catalyzed by lanthanide(III) trifluoromethane sulfonates (Ln(OTf)3, triflates [24]). Some examples are reported in Schemes 6.12 and 6.13. With respect to uncatalyzed reactions, the lanthanide catalyst allows milder reaction conditions, increases the reaction yield and does not affect the diaster-eoselectivity of the reaction, but influences the regiochemistry as in the cycloaddition of 25 with 1,3-dimethyl-1,3-butadiene (Schemes 6.10 and 6.12). These results have been applied [24b-d] to the synthesis of azasugars (Scheme 6.14). 

Streith J., Defoin A. Aza Sugar Syntheses and Multi-Step Cascade Rearrangements Via Hetero Diels-Alder Cycloadditions With Nitroso Dienophiles Synlett 1996 189-200... 

Substituted 1,2,3,4-tetrahydroquinolines (e.g., 61) are formed with high regio- and stereoselectivity in high yield by intermolecular [A+2] cycloadditions of cationic 2-aza-butadienes and various dienophiles <95CC2137,96SL34>. 

Berlin JM, Eu GC (2008) Enantioselective nucleophilic catalysis the synthesis of Aza-P-lactams through [2 -I- 2] cycloadditions of ketenes with azo compounds. Angew Chem Int Ed 120 7156-7158... 

The lithium derivative of di-f-butylfluorosilyl-2,6-diisopropylphenyl-amine reacts with 2-methyl-2-propenal in two competing ways. In a [2 + 4] cycloaddition, an oxa-3-aza-2-sila-5-cyclohexene is formed and in a [2 + 2] cycloaddition, 2-methyl-2-propenyl-Af-(2,6-diisopropylphenyl)-imine is generated via an (SiNCO)-ring intermediate.18 36... 

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

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