User:Minihaa/Pericyclic and Related Rearrangements

See: Azide

Allene azides
Reactions of allenes with various dipoles were reviewed recently by Pinho e Melo.108 From a purely geometrical point of view, the intermolecular cycloaddition between an allene and azide can lead to the formation of either out- or in-triazolines 27–28, as defined in Scheme 7. Importantly, the out-isomers but not the in- ones have conjugated C=C and N=N bonds.

When the substituents R and R' differ, chemoselectivity issues (bond a vs. b) can arise to further complicate the process. As mentioned earlier, the two bonds of the allene require the reagent to approach in two different planes that are oriented at 90° to each other.

The seminal report on allene−azide cycloadditions was published by Bleiholder and Schechter in 1968.109 They found that tetramethylallene 29 reacts with electron-deficient azides at RT to give crystalline out-triazolines 30 as the only products (Scheme 8). Heating of the latter produced azadienes 31.

It was known at the time of Bleiholder and Schechter's report that treatment of 32 with strong bases gives “allenimines" 33 (later dubbed methylene aziridines, MAs; Scheme 9)110 but, despite the expectations, these compounds were not observed in photochemical or thermal reactions of the aforementioned triazolines 30.

The rate and regiochemistry of allene–azide reactions are highly sensitive to steric factors. For example, chiral macrocyclic allene R-(+)-34 was converted enantio- and regioselectively into the out-triazoline S-(+)-35, whereas more sterically accessible allene 36 gave a mixture of three products: 37, 38, and 39 (Scheme 10).111

As can be seen from these examples, intermolecular reactions between allenes and azides generally favour the out-triazoline products with conjugated C=C and C=N bonds. High levels of stereocontrol as well as quantum chemical computations support the concerted cycloaddition mechanism.112

In-depth studies on unstable azoles and aziridines were performed by the group of Quast113–123 who demonstrated that non-conjugated in-triazoles, such as 40, undergo thermal or photochemical decomposition into E-imine 41 (Scheme 11).113,115 Relatedspecies 43 was isolated from the reaction of pyrazole derivative 42.

It was shown that various MAs 44 undergo valence isomerisation into 45 and 48 at increased temperatures (Scheme 12).114,123 Further reaction afforded isocyanides 47 and alkenes 46; these are thought to arise from the (2+1)-cycloreversion of cyclopropane imine 45.113–116 Similar products were also reported more recently by Huisgen.124

The mechanisms of these remarkable reactions have been extensively investigated by Quast who proposed the formation of delocalised diradical species 49 (Scheme 13), dubbed “azatrimethylenemethanes” (ATMMs).115,123 These are related to the better known trimethylenemethane (TMM), 51, first obtained by Dowd by the photolysis of Δ1-pyrazoline 50.125

Interestingly, while Quast and others (see below) advocate the diradical structure for the products of nitrogen elimination, several studies have been published that postulate ionic intermediates.126,127 Shea investigated the decomposition of polycyclic adducts 52 into compounds 54 and 55 and proposed zwitterionic species 53 (Scheme 14).128 High-level computations on various aza-analogs of TMM indicated inherent computational issues with ATMMs and the intermediate nature of these species between purely diradical TMM (51) and zwitterionic 2-oxyallyl species.129

As of 2013, the group of Feldman is the most active in the field of allene–azide cycloadditions.112,130–137 This group showed that conjugated allene azides 56 can be transformed into bicyclic products 59, presumably via triazolines 57 and diradical intermediates 58 (Scheme 15).136 Extensive quantum chemical computations were performed to support the proposed diradical mechanism.112,135 Azadienes 59 were rather unstable and had to be immediately hydrogenated136 or trapped in situ with TMSCN.130 Functionalised azadiene (not shown), related to 59, was later elaborated into the natural product meloscine.137

In a related project, fully conjugated allene azides 60 were transformed into indoles 61 and 62 (Scheme 16).134 The reactions could be induced thermally (110 °C) or photochemically. Interestingly, CuI catalysis favoured the formation of indole compounds 61.

Huang et al. developed a conceptually related cascade synthesis of oxindoles.138 Allene azides 63, obtained by the Pd-catalysed coupling between 3-iodocyclohexen-2-one and a propargylic ether, were transformed in situ into ATMM 65; ring closure and hydrolysis afforded oxindoles 67 in 49−76% yield (Scheme 17).

Reactions of inorganic azides with electronically biased allenes often give Michael addition products. For example, the reaction of electron-deficient allene 68 with NaN3 delivered conjugated azide 69 (Scheme 18).139 The latter was converted into substituted pyrrole 72 by gentle heating (80 °C).

Reactions of sulfonyl allene azides 73 with Bu3SnH at RT furnished 1-pyrrolines 74 in good to excellent yields, presumably by the 1,4-addition of the in situ formed amine (Scheme 19).49

Transition-metal-catalysed reactions are also reported (Scheme 20).140,141 Cheng obtained allylic azides 75 and 76 by a three-component coupling between terminal allenes, aryl iodides, and TMSN3, in the presence of Pd(dba)2 complex.141 Grigg developed a cascade process, in which the intermediate azides 78 are trapped by nearby C=C bond to give triazolines 79. An increase in the reaction temperature from 70 to 100 °C led to the concomitant loss of N2 and formation of isoquinolines 80.140