Amination azodicarboxylate

The conversion of an alcohol to an amine can be achieved in a one-pot reaction the alcohol 1 is treated with hydrazoic azid (HN3), excess triphenylphosphine and diethyl azodicarboxylate (DEAD). The initial Mitsunobu product, the azide 14, further reacts with excess triphenylphosphine to give an iminophosphorane 15. Subsequent hydrolytic cleavage of 15 yields the amine—e.g. as hydrochloride 16 ... 

In an indirect amination process, acyl halides are converted to amino acids. Reaction of the acyl halide with a chiral oxazolidinone leads to a chiral amide, which reacts with the N=N unit of a dialkyl azodicarboxylate [R"02C—N=N—CO2R ]. Hydrolysis and catalytic hydrogenation leads to an amino acid with good enantioselectivity. ... 

Treatment of the cyclic ketene aminal 267 with diethyl azodicarboxylate results in formation of the reduced ring system 268 (Equation 52), probably via an initial aza-ene reaction, followed by fragmentation and ring closure <2002T7791>. 

A catalytic asymmetric amination reaction has been developed using Cu(2+) catalysts (246). The azodicarboxylate derivative 392 reacts with enolsilanes in the presence of catalyst 269c to provide the adducts in high enantioselectivity, Eq. 213. As observed in the Mukaiyama Michael reactions, alcoholic addends proved competent in increasing the rate of this reaction. Indeed, in the presence of tri-fluoroethanol as additive, the reaction time decreases from 24 to 3 h. 

Silylated primary allylic amines, e.g. CH2=CHCH2N(SiMe3)2, are produced from allylic chlorides and the mixed reagent AgI/LiN(SiMe3)2205. The formation of allylic amines from olefins by the ene reaction is shown in equation 77. The ene adducts 205 from bis(2,2,2-trichloroethyl) azodicarboxylate are converted into 206 by zinc dust in acetone/acetic acid206. 

It is true that highly enantioselective reactions are possible with proline in the asymmetric a-amination of aldehydes by azodicarboxylates and in a-oxidation with nitrosobenzene. However, good rather than excellent yields and enantioselectivities are more common in intermolecular Michael and aldol reactions. Moreover, the high catalyst loadings required for proline-catalyzed aldol reactions (up to 30%), and low TOFs (from hours to days to achieve a good conversion, even at a high catalyst... 

In an indirect amination process, acyl halides are enantioselectively converted to amino acids.176 The key step involves addition to the N=N bond of a dialkyl azodicarboxylate 22. 

The Mitsunobu reaction is usually only suitable for the alkylation of negatively charged nucleophiles rather than for the alkylation of amines, and only a few examples of such reactions (mainly intramolecular N-alkylations or N-benzylations) have been reported (Entry 15, Table 10.2). Halides, however, are very efficiently alkylated under Mitsunobu conditions, and it has been found that the treatment of resin-bound ammonium iodides with benzylic alcohols, a phosphine, and an azodicarboxylate leads to clean benzylation of the amine (Entry 9, Table 10.3). Unfortunately, alkylations with aliphatic alcohols do not proceed under these conditions. The latter can, however, also be used to alkylate resin-bound aliphatic amines when (cyanomethyl)-phosphonium iodides [R3P-CH2CN+][r] are used as coupling reagents [62]. These reagents convert aliphatic alcohols into alkyl iodides, which then alkylate the amine (Entry 10, Table 10.3). 

With tetracyanoethylene the 1-methyl derivative of 63 (R = H) led to compounds of type 226 with diethyl azodicarboxylate, to compounds of type 226 and with diethyl azodicarboxylate, to compounds of type 227.114 The 3-formyl and the 3-aminomethylene group of the pyrido[l,2-a] pyrimidines (222 R = H and 224) underwent condensation with compounds containing an active methylene group.297-299,303 The 3-formyl group has also been reacted with primary amines,285 hydrazines.98,260,285 semicarbazide and thosemicarbazide.98... 

A catalytic asymmetric amination of enecarbamates has been attained using a chiral Cu(II) complex of diamine (210) as catalyst. Thus, azodicarboxylates have been shown to react with various enecarbamates (208) derived from aromatic and aliphatic ketones and aldehydes to provide acylimines (209) in good yields with high enantioselectivity (<99% ee). The catalyst loading required for high enantioselectivity was generally low (0.2 mol% in some cases).259... 

C-Nucleophiles have recently been added asymmetrically to azodicarboxylates as Michael-acceptors, resulting in a-amination of the nucleophilic component. Examples of this type of reaction, which is based on activation of the aldehyde or ketone component by enamine formation, are summarized in Scheme 4.27. Please note that this type of reaction is covered in more detail in chapter 7 of this book. 

The proline-catalyzed direct asymmetric a-amination of aldehydes was reported in 2002 by both List [46] and j0rgensen [47]. As shown in Scheme 4.27 a variety of azodicarboxylates 58 can be added to aldehydes, affording the a-aminated products 59 in very good yields and with excellent ee. The experimental procedures are, furthermore, very convenient. The primary addition products 59 are configuration-ally unstable and are usually either reduced to the corresponding alcohols 60 (e.g. 

To start with the a-amination of ketones, the Jorgensen group reported a highly enantioselective addition of ketones, 1, to azodicarboxylates, 3, as N=N component [5], The l amino acid L-proline was found to be a highly efficient catalyst. In a first screening using a model reaction (Scheme 7.2) it was found that diethyl... 

Extension of this proline-catalyzed a-amination to the use of aldehydes as starting materials has been described independently by the Jorgensen and List groups [6, 7]. The principle of the reaction and some representative examples are shown in Scheme 7.4. The practicability is high - comparable with that of the analogous reaction with ketones described above. For example, in the presence of 5 mol% L-proline as catalyst propanal reacts with azodicarboxylate 3a at room temperature in dichloromethane with formation of the a-aminated product 5a in 87% yield and with 91% ee [7]. Good yields and high enantioselectivity can be also obtained by use of other types of solvent, e.g. toluene and acetonitrile. The products of type 5 were isolated simply by addition of water, extraction with ether, and subsequent evaporation. 

The a-amination of aldehydes and subsequent reduction to form oxazolidinones (Scheme 7.6) was developed by the Jorgensen group [7]. In the presence of 10 mol% L-proline as catalyst a variety of aldehydes reacted with azodicarboxylates, 3a and 3a, affording the oxazolidinones 7 after subsequent reduction with borohydride and cyclization. Selected examples of the synthesis of products 7, which were obtained in yields up to 92% and with enantioselectivity up to 95% ee, are shown in Scheme 7.6. 

OH - —NTfCHj. Primary or secondary alcohols are converted to protected secondary amines by this triflamide under Mitsunobu conditions (triphenylphos-phine, diethyl azodicarboxylate) in 70-86% yield. The reaction proceeds with inversion, and is useful for preparation of optically active secondary amines. 

The direct a-amination of aldehydes by azodicarboxylates as the electrophilic nitrogen source can be catalyzed by, for example i-proline 3a, to give the a-hydrazino aldehydes 4 having (R -configuration in moderate to good yields and with excellent enantioselectivities (89-97% ee) (Scheme 2.27) [4]. The optically active a-hydrazino aldehydes 4 are prone to racemization, and it was found beneficial to reduce them directly with NaBFU to stereochemical stable compounds which, by treatment with NaOH, can cyclize to form the N-amino oxazolidinones 5 in a one-pot process. The N-amino group in 5 could be cleaved with Zn/acetone to give the oxazolidinone 6 (Scheme 2.27). 

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