Allenes reactions with nitriles

In the first method a secondary acetylenic bromide is warmed in THF with an equivalent amount of copper(I) cyanide. We found that a small amount of anhydrous lithium bromide is necessary to effect solubilization of the copper cyanide. Primary acetylenic bromides, RCECCH Br, under these conditions afford mainly the acetylenic nitriles, RCsCCHjCsN (see Chapter VIII). The aqueous procedure for the allenic nitriles is more attractive, in our opinion, because only a catalytic amount of copper cyanide is required the reaction of the acetylenic bromide with the KClV.CuCN complex is faster than the reaction with KCN. Excellent yields of allenic nitriles can be obtained if the potassium cyanide is added at a moderate rate during the reaction. Excess of KCN has to be avoided, as it causes resinifi-cation of the allenic nitrile. In the case of propargyl bromide 1,1-substitution may also occur, but the propargyl cyanide immediately isomerizes under the influence of the potassium cyanide. 

A wide variety of five-membered zirconacydes 8 may be formed by the formal co-cycliza-tion of two 7i-components (3 and 6 alkene, alkyne, allene, imine, carbonyl, nitrile) on zir-conocene ( Cp2Zr ) (Scheme 3.2) [2,3,8]. The co-cydization takes place via the r 2-complex 5 of one of the components, which is usually formed by complexation of 3 with a zircono-cene equivalent (path a) ( Cp2Zr itself is probably too unstable to be a true intermediate) or by oxidation on the metal (cyclometallation/p-hydrogen elimination) (path b). Two additional routes to zirconocene r 2-complexes are by the reverse of the co-cyclization reaction (i. e. 8 reverting to 5 or 9 via 7), and by rearrangement of iminoacyl complexes (see Section... 

Dipolar cycloadditions to electron-deficient allenes are not regioselective, taking place at the electron-poor C=C bond, in all cases. For example, the reaction of 372 with nitrile oxide 378 furnishes a mixture of products 379-383 [356], Obviously, 379, 380 and 381 result from different [2 + 3]-cycloadditions followed by tautomer-ism, whereas 382 and 383 are formed from the primary products of the 1,3-dipolar cydoaddition via addition of a second equivalent of 378 to the remaining exocyclic C—C bond. 

Besides simple enones and enals, less reactive Michael acceptors like /3,/3-disubstituted enones, as well as a,/3-unsaturated esters, thioesters, and nitriles, can also be transformed into the 1,4-addition products by this procedure.44,44a,46,46a The conjugate addition of a-aminoalkylcuprates to allenic or acetylenic Michael acceptors has been utilized extensively in the synthesis of heterocyclic products.46-49 For instance, addition of the cuprate, formed from cyclic carbamate 53 by deprotonation and transmetallation, to alkyl-substituted allenic esters proceeded with high stereoselectivity to afford the adducts 54 with good yield (Scheme 12).46,46a 47 Treatment with phenol and chlorotrimethylsilane effected a smooth Boc deprotection and lactam formation. In contrast, the corresponding reaction with acetylenic esters46,46a or ketones48 invariably produced an E Z-mixture of addition products 56. This poor stereoselectivity could be circumvented by the use of (E)- or (Z)-3-iodo-2-enoates instead of acetylenic esters,49 but turned out to be irrelevant for the subsequent deprotection/cyclization to the pyrroles 57 since this step took place with concomitant E/Z-isomerization. 

Hydration of attenic nitriles. 4,4-Dialkyl-substitutcd allenic nitriles (1) are converted into allenic amides (2) in 60 70% yield by reaction with hydrogen peroxide in alcoholic sodium hydroxide. 

Similarly, treatment of ynones with DECP and LiCN leads to the corresponding cyanophosphate, which, on reaction with cuprates in THF at low temperature, give the allenic nitrile by elimination of phosphate. Only a few reports describe the properties of DECP as a phosphorylation reagent for imidazoline nitrogen atoms, phenols, and Grignard reagents. ... 

A synthesis of 7,8-dioxygenated isoquinolines (found in cularine alkaloids) requires o-metallation of the Af-protected -phenylethylamine. The primary amine is protected by reaction with two equivalents of trimethylsilyl chloride. Phenylhydroxylamine and the allenic nitrile (53.7) react in boiling ethanol over 48 h to give a high yield of 4-aminoquinoline—an important intermediate for the synthesis of some antimalarial drugs. 

The mode of reaction of allenes with 1,2-diamines seems to be strongly dependent on the substituents on the allene. Allenic nitriles give imidazoles via double Michael addition but the 1,3-diester (114), on reaction with o-phenylenediamine, gave only the 1,5-benzodiazepine (116). The enamine intermediate (115) apparently strongly favours a 1-exo-trig cyclization over the competing 5-exo-trig alternative. ... 

Reactions with conjugated enynes as dienes in Diels-Alder reactions yield cyclohexadiene or benzene products on reaction with alkene or alkyne dienophiles, respectively. These reactions proceed via a stepwise mechanism to avoid formation of a cyclic allene and are referred to as dehydro-Diels-Alder reactions. In 2008, Barluenga and Aguilar demonstrated that gold catalysts promote intermolecular hetero-dehydro-Diels-Alder reactions between dienynes and nitriles. Dienyne 99 combines with phenyinitrile (100) to afford substituted pyridine 101. ... 

The polymerization and the reaction with acyclic unsaturated compounds are considered to take place on the coordination sites of the active catalyst species. Therefore, the effect of various compounds described above reflect, at least in part, their relative ability of coordination to the active species. The effect of acetylenes and allenes as well as that of a,6-un-saturated esters and nitriles may reasonably be explained by their stronger power of coordination in com comparison with that of the norbomene double bond. 

The liganded titana allene, L2Ti=C=CH2, also reacts with nitriles via a [2+2] cycloaddition reaction across the C=N bond to give the four-membered ring cycloadducts 67. ... 

Allenes add nitrile oxides either to one or two double bonds. For mono- and 1,1-disubstituted allenes, relative activity of the two bonds depends on the nature of substituents. The reaction (Scheme 1.18) of N-propadienylanilines 54 with 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide proceeds site- and regioselectively to give 5-substituted 4-methylene-4,5-dihydroisoxazoles 55, which add a second molecule of nitrile oxide to afford 4,5/-spirobi-(4,5-dihydroisoxazoles) 56. Dihy-droisoxazoles 55 isomerize to 4-(2-aminobenzyl)isoxazoles 57 via a Claisen-type rearrangement (224). 

The study of the intramolecular nitrile oxide—allene cycloaddition shows, in particular, that dehydration of nitroallene 339 by PhNCO, generates a nitrile oxide in situ, which gives isoxazoline 340 (Scheme 1.36). Thus, the reaction of the more remote double bond with the formation of six-membered ring prevails (405). 

Zecchi and co-workers also reported 1,3-dipolar cycloadditions with nitrogen-substituted allenes. As illustrated in Scheme 8.75, the expected isoxazoline derivatives 285 were obtained by [3 + 2] cycloaddition reaction of aminoallenes 246 and nitrile oxide 284 [141, 142], Bis-adducts 286 became the major products when 2equiv. of nitrile oxide 284 were applied with prolonged reaction times. 

At temperatures between -33and 0°C, l-cyano-l,2-allenes 574 can react with primary or secondary amines to afford unconjugated enaminic nitriles 575, which can be converted to conjugated enamines 576 at 200 °C [264, 265], The corresponding reaction of ammonia is relatively slow and was conducted at 60-70 °C to afford 3-amino-4-ethyl-2-hexenenitrile 577 together with a small precentage of iminyl nitrile 578 [264, 265],... 

Not only heteroatom-H bonds but also activated C-H bonds can add to the jr-system of an allene. Since carbon lacks a free electron pair, the transition metal catalyst must first activate the C-H bond the new species formed will then react with the C=C double bond. For efficient activation of that kind, two acceptors (typically esters, nitriles and/or sulfones) are necessary. In accord with this mechanistic picture is the fact that the reaction does not benefit from an additional base (which would deproto-nate the pronucleophile). Hence neutral conditions are even better. 

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