Azodicarboxylates, with alkenes

Brimble, M.A. and Heathcock, C.H., Allylic amination by the Lewis-acid-mediated ene reaction of diethyl azodicarboxylate with alkenes, /. Org. Chem., 1993, 58(19), 5261-5263. 

Other nitrogen compounds, among them hydroxylamine and hydroxylamines, " hydrazines, and amides (15-9), also add to alkenes. Azodicarboxylates (Boc-N= N-Boc) react with alkenes, in the presence of PhSiH3 and a cobalt catalyst, to give... 

Electrophilic azo compounds such as diethyl azodicarboxylate and triazoline-3,5-dione also give ene-type products on reaction with alkenes. 

When other acceptor systems such as tetracyanoethylene, ethyl propiolate, dibenzoylacetylene, or dimethyl azodicarboxylate were reacted with 41, no additional products were formed. Accordingly, the scope of the reaction for the nucleophilic addition of 41 to electron-poor alkenes, alkynes, and diazo compounds is quite narrow. 

This work has been extended from aryl and alkyl substituted systems (42) (R = aryl, alkyl) to analogues where R is an amino group, so giving access to synthetic equivalents of the nonstabilized amino nitrile ylides (45). Adducts were obtained in good-to-moderate yield with A-methyhnaleimide (NMMA), DMAD, electron-deficient alkenes and aromatic aldehydes (27,28), and with sulfonylimines and diethyl azodicarboxylate (29). Similarly the A-[(trimethylsilyl)methyl]-thiocarbamates (46) undergo selective S-methylation with methyl triflate and subsequent fluorodesilylation in a one-pot process at room temperature to generate the azomethine ylides 47. 

It seemed prudent that the same ethers be examined in the absence of potentially labile functionality, thus removal of unsaturation in 262 and 263 was considered. Hydrogenation of 259 over Pd/C or Pt was unsuccessful in either case reduction of the peroxide group was problematical. Hydrogenation over Wilkinson s catalyst gave a new product, but with the unsaturation retained. While selective alkene hydrogenation can sometimes be achieved in the presence of a peroxide bond, the double bond of 259 was apparently too hindered in this case. Diimide, on the other hand, worked reasonably well for this reduction. Thus, treatment of 259 in dichlo-romethane solution with potassium azodicarboxylate followed by addition of acetic acid led, after several days, to roughly 60% conversion of 259 to the saturated version, 264. Now, ether formation as before provided the saturated methyl and benzyl ethers 265 and 266, respectively, in good yields. 

Carreira and coworkers recently investigated hydrohydrazination reactions of olefins 201 with azodicarboxylate 202 (Fig. 56) [300, 301]. Similar to the hydration described above, 2 mol% of Mn(dpm)3196 as the catalyst and phenylsilane as the reducing agent proved to be optimal to obtain alkylhydrazines 203 in 45-98% yield. The manganese catalyst is considerably more reactive than cobalt catalysts applied in the same reaction (see Part 2, Sect. 5.7). Even tetrasubstituted alkenes underwent... 

Diols are directly converted into oxiranes with Ph3P or other phosphines in the presence of diisopropyl azodicarboxylate (Mitsunobu reaction). Simple alkenes can be converted into nonracemic epoxides in high yields and with excellent ee values via a two-step sequence of asymmetric dihydroxylation and Mitsunobu cyclodehydration of the intermediate diol (Scheme 18) <20010L2513>. These reactions give best results using electron-poor alkenes . 

Diethyl azodicarboxylate (DAD) behaves like a reactive electrophilic alkene and attack on a substituted cyclohexanone enamine can occur from an axial or equatorial direction depending on the steric effects in the transition state. For example, DAD reacts with 159 to give 160 by equatorial attack, together with 161 (ratio 1 9), whereas the... 

Both cyclic and acyclic R-N = N — R systems undergo ene reactions with simple alkenes, and most studies have employed either A -substituted triazolinediones 1 or azodicarboxylate diesters 3 to produce the triazolidines 2 and the hydrazines 4, respectively. 

This reaction picture is somewhat clouded by a recent report detailing the stereochemical outcome of the reactions of the alkenes 6 and 7 with diethyl azodicarboxylate and N-phenyl-triazolinedione to produce the two sets of diastereomers 8, 9 and 10, IT, respectively10. 

The ene reaction of an azodicarboxylate ester was first observed in 196218-19 as a process competing with cycloaddition to dienes, but little additional work has been done on the ene reaction with simple alkenes. An elegant study in 1976 provided evidence for a concerted, suprafacial reaction between dimethyl azodicarboxylate and (S)-(Z)-l-deutero-4-methyl-l-phenyl-2-pentene (15) based on the direction and high level of chirality transfer observed20. 

Use of cyclopentene, frans-hex-3-ene and frans-oct-4-ene afforded the ene adducts in good yield with a diastereomeric excess of 86 14 in each case. The diastereoselectivity observed using di-(—)-( / ,25)-2-phenyl-l-cyclohexyl diazenedicarboxylate as a chiral azo-enophile offered a significant improvement over the use of di-(-)-menthyl azodicarboxylate where the level of asymmetric induction achieved in Lewis acid-mediated ene reactions with simple alkenes was not impressive. Moreover, it proved difficult to cleave the N-N bond in the menthyl ester azo-ene adducts whereas sodium/liquid ammonia was used to smoothly cleave the N-N bond in the diacylhydrazine adducts formed using di-(—)-(l/ ,25)-2-phenyl-l-cyclohexyl diazenedicarboxylate as azo-enophile. 

Azodicarboxylates are recognized for their ability to participate as 2ir components of HOMOdi e-con-trolled Diels-Alder reactions with dienes and for their participation in ene reactions with reactive al-kenes. 489 j, addition, electron-rich or reactive simple alkenes that do not contain a reactive allylic hydrogen atom have been shown to participate in competitive [2 + 2] and [4 + 2] cycloaddition reactions with azodicarboxylates in which the observed course of the reaction is dependent upon the solvent polarity and nucleophilic character of the alkene (Table 13). As may be anticipated, alkoxycarbonyl-aroyldiimides (4), diaroyldiimides (5), and aiylaroyldiimides (6) participate with increasing selectivity as 4tr components of [4 + 2] cycloaddition reactions. 

The reaction has also been accomplished under extremely mild conditions (a few seconds at 0°C) with PPh3 and diethyl azodicarboxylate EtOOC-N=N-COOEt. " In a related procedure, p-lactones undergo thermal decarboxylation to give alkenes in high yields. The reaction has been shown to be a stereospecific syn-eUmination. There is evidence that this reaction also involves a zwitterionic intermediate. ... 

In the gas phase, 2 is a thermally very stable compound up to 850 °C. Pyrolysis at 880°C/10 Torr generates styrene (55-62%) and o-xylene (6%) along with small amounts of phenylacetylene, benzene, toluene and unidentified hydrocarbons. Cycloaddition reactions with dienophiles were among the first reactivity studies on 2 they were of course driven by the expectation to generate a cyclobutadiene structure by a twofold (4 + 2) cycloaddition. However, while 2 reacts readily with electron-deficient alkenes such as TCNE, A -phenyhnalermide, 4-phenyl-l,2,4-triazolinedione and diethyl azodicarboxylate to form 1 1 adducts 115, a second Diels-Alder reaction... 

This method is unusually mild, using neutral conditions and low temperatures (20 °C and less). It tolerates a number of functional groups in the components (e.g. acetals, esters, alkenes, etc.)- The alcohol, the carboxylic acid and triphenylphosphine are treated dropwise in an inert solvent (dichloromethane, THF, ether) with diethyl azodicarboxylate (DEAD). The ester is formed rapidly. However, tedious chromatography is frequently required to remove the by-products, triphenylphosphane oxide and hydrazo ester. The main value of the reaction lies in the clean inversion of configuration at a secondary carbinol center and in its selectivity towards primary hydroxy groups (vide infra). Inversions are usually performed with benzoic or p-nitrobenzoic acid. The benzoates are purified and saponified with aqueous base to furnish the inverted alcohols in overall yields of ca. 50%. Elimination is the main side reaction. Thus, from (44) 75% of the desired Sn2 product (45) is formed, along with 25% of the elimination product (46) (equation 19). The mechanism of the reaction has been clarified to the point that betaine (47) is the pri-... 

Hydroxymethyl-1,4-benzodioxin (137) obtained in 80% yield by reduction of ethyl 1,4-benzo-dioxin-2-carboxylate (39) with lithium aluminum hydride in refluxing ether <91TL5525> reacted with zinc azide bis-pyridine complex under Mitsunobu conditions (triphenylphosphine, diisopropyl azodicarboxylate) to yield exclusively compound (138) in 75% yield. Otherwise, (137) was first reacted with zinc iodide under the same conditions until complete transformation of the starting material into the mixture of regioisomers (139) and (140) excess of dry piperidine was then added to the crude reaction medium to yield the alkenic analogue (141) of Piperoxan <89TL1637>. 

A radical mechanism is at least partially responsible for the reaction of alkenes with azodicarboxylates [58-60]. Addition of phenyl and methyl radicals to dialkyl azodi-carboxylates was investigated from a mechanistic point of view [61, 62]. Wamhoff reported the thermal and photochemical addition of ethers to 4-aryl-1,2,4-triazoline-... 

Allyl carbamates. By catalysis with SnCU the reaction temperature of the ene reaction of alkenes and diethyl azodicarboxylate may be lowered to —60°C. The adducts are converted to allylic carbamates on reduction with Li in liquid ammonia. 

Alkenes. j3-Hydroxy carboxylic acids are converted into alkenes in fair to good yield by treatment with triphenylphosphlne and diethyl azodicarboxylate (equation I). The reaction involves loss of CO2 and HaO (decarboxylative dehydration). 

Ma has developed a three-component allene carboamination reaction for the stereoselective synthesis of 2,5-as-disubstituted pyrrolidine derivatives [54]. A representative transformation involving allene 58, 4-iodoanisole, and imine 59 that generates 60 in 90% yield is shown below (Eq. (1.28)). The reaction is believed to proceed through the intermediate Jt-allylpalladium complex 62, which is formed by carbopalladation of the alkene to give 61 followed by addition of the malonate anion to the activated imine. Intramolecular capture of the allylpalladium moiety by the pendant nitrogen nucleophile affords the pyrrolidine product. A related asymmetric synthesis of pyrazolidines that employs azodicarboxylates as one of the electrophilic components has also been reported [55]. The pyrazolidine products are obtained with up to 84% ee when chiral bis oxazolines are employed as ligands. 

A similar system was proposed by Marko based on CuCl, phenanthroline, di-tert-butyl azodicarboxylate (DBAD) and N-methylimidazole (NMI) as additives showing efficient oxidation of both primary and secondary alcohols to carbonyl compounds, with molecular oxygen or air as the oxidant releasing water as the sole by-product. The catal3dic system exhibits good tolerance of the presence of electron-rich alkenes, thioethers and pyridine moieties, which could be involved in other oxidation reactions but remain unaffected by the catalyst. In the case of... 

Due to the nucleophilicity of a-aminoaUcyl radical, it is supposed to add to electron-deficient alkenes. This assumption was first achieved by Nishibayashi [50] and Reiser [51] in early 2012 (Scheme 3.12). They reported visible-Ught-mediated addition of a-aminoalkyl radicals derived from tertiary amines to Michael acceptors (unsaturated esters and vinyl ketones). Also, radical addition to acrylate derivatives was later accomplished (Scheme 3.12) [52]. As a follow-up work, Nishibayashi et al. developed visible-light-promoted radical C(sp )-H amination of benzocyclic tertiary amines using di-terr-butyl azodicarboxylate as nitrogen source (Scheme 3.12) [53]. In 2013, Yu et al. found that AA -dimethylaniline derivatives could react with A-aryl- and A-benzyhnaleimides to give tetrahydroquinoline products with air as oxidant (Scheme 3.12) [54]. Unfortunately, the other olefins, such as furan-2,5-dione, diethyl maleate, methyl acrylate, and l-phenylprop-2-en-l-one, fail to undergo this transformation. The mechanistic... 

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