Diisopropyl azodicarboxylate, reaction with

Pavan Kumar et al. <2006NJC717> investigated the reaction of diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD) with cyclic phosphates or phosphoramides in order to determine the structural preferences in spirocyclic penta- and hexacoordinate aminophosphoranes. They found that sulfur would coordinate to phosphorus to form the [3.3.0] bicyclic compounds 94-96. 

The 3-methyl- and 3-phenyl-l,2,3-oxadiazolinium salts 96 and 97 are capable of oxidizing thiols to disulfides <1995MI817>. New dihydro-1,2,3-benzoxadiazoles, prepared by the reaction of 1,2-benzoquinones with diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD) in the presence of triphenylphosphine (Section 5.03.9.4), have been shown to undergo catalytic hydrogenolysis to give phenols (Equation 12) <20050L5139>. 

We were not able to obtain any cycloadduct from unactivated 2-azadienes 139 and esters of acetylenedicarboxylic acid. However, we found that 139 did cycloadd to typical electron-poor dienophiles such as esters of azodicarboxylic acid and tetracyanoethylene (Scheme 62). Thus, diethyl and diisopropyl azodicarboxylates underwent a concerted [4 + 2] cycloaddition with 139 to afford in a stereoselective manner triazines 278 in 85-90% yield (86CC1179). The minor reaction-rate variations observed with the solvent polarity excluded zwitterionic intermediates on the other hand, AS was calculated to be 48.1 cal K 1 mol-1 in CC14, a value which is in the range of a concerted [4 + 2] cycloaddition. Azadienes 139 again reacted at room temperature with the cyclic azo derivative 4-phenyl-1,2,4-triazoline-3,5-dione, leading stereoselectively to bicyclic derivatives 279... 

Diols are directly converted into oxiranes with Ph3P in the presence of diisopropyl azodicarboxylate (Mitsunobu reaction) (8isi). 

Employing the Mitsunobu reaction with diisopropyl azodicarboxylate and triphenyl-phosphine, aminoacylserine (in contrast to aminoacylthreonine) is converted into (ami-noacyl)oxazolidine-2-carboxylic acid. 54 By the same procedure a/Zo-threonine peptides are converted into the oxazoline derivatives, whilst the threonine peptides are apparently converted into the aziridines in good yields. 86 ... 

Various p-amino thiols are synthesized from the corresponding P-amino alcohols 1 by activation of the hydroxy group to form a tosylate intermediate 2 and then conversion into a thioester 3 5 or direct thioacetylation of the hydroxy group of 1 using the Mitsunobu reaction with diisopropyl azodicarboxylate, triphenylphosphine, and thiolacetic acid as reagents (Scheme l). 6,7 The thioesters 3 are then hydrolyzed and the corresponding disulfide derivatives 4 are produced by iodine oxidation. 7 ... 

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 . 

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>. 

The highly substituted 5,6-dihydro-4//-l,3,4-oxadiazine (264 R = Pr") is formed as a by-product (20%) along with benzil monoxime (40%) on subjecting the O-benzylated monoxime of benzoin (PhCH(OH)C(Ph)=NOCH2Ph) to a Mitsunobu reaction (PhjP and diisopropyl azodicarboxylate) <87JOC4978>, Substitution of the diisopropyl by the diethyl ester raises the yield of oxadiazine (264 R = Et) to 50%,... 

A modified Mitsunobu procedure in which 63 is first treated with the preformed complex 68 (prepared by reaction of triphenylphosphine and diisopropyl azodicarboxylate) and then cesium thioacetate leads to significant racemization [17]. However, if the free acid is reacted instead with an appropriate thioacid (rather than the ester and a cesium salt), optical yields improve significantly. Thus, thioacetylation of (S)-l can be accomplished by treating it with 68 followed by the addition of thioacetic acid in THF to provide in 48% yield (5)-2-(acet-ylthio)-2-phenylacetic acid (69) with 84% ee after recrystallization. The low yield is due in part to the unavoidable formation to the extent of at least 50% of a viscous, polymeric material. The reaction is complete in minutes, however, and proceeds with retention of configuration. Presumably this is a result of a double inversion mechanism that passes through an a-lactone. Interestingly, the corresponding reaction with lactic acid does occur with inversion [18]. 

This reaction was initially reported by Fukuyama and co-workers in 1995. It is a two-step conversion of primary amines into secondary amines via ortho-nitrobenzenesulfonation in conjunction with the Mitsunobu Reaction and subsequent removal of the o-nitrobenzenesulfonyl group by thiophenol. Therefore, this reaction is generally known as the Fukuyama amine synthesis. In addition, it is also referred to as the Fukuyama-Mitsunobu A -alkylation," Fukuyama-Mitsunobu alkylation, Fukuyama-Mitsunobu condition, Fukuyama-Mitsunobu procedure, or Fukuyama-Mitsunobu Reaction. In this reaction, the o-nitrobenzenesulfonyl-protected amine is alkylated with alcohol in the presence of PPhs and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD), and the deprotection occurs in a very mild condition (almost neutral ). The o-nitrobenzenesulfonyl group is simply called the Fukuyama sulfonamide protecting groupThis reaction has become a versatile method... 

This reaction was first reported by Mitsunobu in 1967. It is the alkylation of compounds with active protons by using primary or secondary alcohols as the alkylating agents in combination with triphenylphosphine and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD), to form molecules like esters, ethers, thioethers, and amines. Therefore, this reaction is generally known as the Mitsunobu reaction or Mitsunobu coupling. In addition, the specific reaction for forming esters by means of DEAD (or DIAD) and PPhs is generally referred to as the Mitsunobu esterification." Occasionally, the Mitsunobu reaction is also called the Mitsunobu transformation (for the conversion of alcohol into amines) or Mitsunobu cyclizafion (for the formation of cyclic compounds). Because of its intrinsic features of stereospecificity, as well as its occurrence in neutral media and at room temperature without a prerequisite activation of alcohol, this reaction has been extensively studied and used to synthesize a variety of compounds since 1970. 

Resin 23 was first swollen in CH2CI2 and, in a manner that parallels the route employed in the solution-phase synthesis, was reacted with a selected benzylsulfonyl chloride and t-BuOLi as a base to afford the corresponding sulfonamide resin 28, containing the first diversity element R. The sulfonamide resin 28 was then reacted under Mitsunobu conditions (PPha (triphenyl phosphine), DIAD (diisopropyl azodicarboxylate), THE, room temperature) with the appropriate alcohols. This process efficiently produced resin 29 and introduced the second diversity element R. Cyclization reaction of resin 29 was promoted by sodium hydride in DMF and led to the formation of the desired thiazolo[4,5-c] [l,2]thiazine resin 30. Treatment of resin 30 with mCPBA in CH2CI2 generated the resin-bound cyclic sulfonamide 31. Finally, the thiazolo[4,5-c][l,2]thiazine derivatives 5 were formed and cleaved from the resin (in a traceless manner" ) by treatment of resin 31 with the corresponding amines (R R" N diversity elements) in respectable yields (34 examples, from 11% to 29% for seven linear steps starting with Merrifield resin 1, Table 10.4). 

Perfluoroalkylated fatty acid 6-esters of sucrose and aa-trehalose were prepared by a reaction of sucrose or a,a-trehalose with a perfluoroalkylated acid, Rf(CH2)rtCOOH (Rf = C4F9, C6F 3, or CgFi7, n = 2, 4, 10) in the presence of triphenylphosphine and diisopropyl azodicarboxylate in j/V,iV-dimethylformamide [262]. The surfactants were used to prepare fluorochemical emulsions intended as intravascular oxygen carriers (see Section 10.4). 

Intermolecular and intramolecular nucleophilic substitution of an alcoholic hydroxy group by the triphenylphosphine/dialkyl azodicarboxylate redox system is widely used in the synthesis and transformation of natural products and is known in organic chemistry as the Mitsunobu reaction.1951 This reaction starts with formation of the zwitterionic phosphonium adduct 19 (Scheme 9) from triphenylphosphine and diethyl (or diisopropyl) azodicarbox-... 

Imino ethers and 2-alkoxybenzthiazolium salts prepared from chiral alcohols react with carboxylic acids to give the esters of the corresponding inverted rdcohols (Scheme 39).7ic.72d,73,75a reaction of a chiral alcohol with a carboxylic acid, DEAD and PhsP affords the ester of the inverted alcohol (Scheme 44). 2 Diisopropyl or dimethyl azodicarboxylate can be used instead of DEAD. Little difference between these reagents has been reported. ... 

The only examples of electrophilic amination of organozinc compounds described in the literature correspond to the reaction of an excess of diethyl/ diisopropyl zinc with several chloroamines [61]. The reaction afforded moderate to low yields of substitution products, often as a mixture of amines [62,63]. On the other hand, electrophilic amination using dialkyl azodicarboxylates has been reported for other nucleophilic species, including lithium enolates and silyl enol ethers [64-70]. 

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