Sodium azide, reaction with allylic acetates

Ally lie substitution of a variety of substrates (such as allyl carbonates or acetates) with carbon- or heteronucleophiles (201) was shown to occur under mild conditions (50-80°C) on the catal3rtic effect [Pd(OAc)2l -I- TPPTS (Scheme 34). In many cases, there was no need for an external base however, reactions of allyl acetates required the presence of (C2H5)3N or l,8-diazabicyclo-5,4,0-undec-7-ene (DBU). Primary and secondary amines, as well as sodium azide and p-toluene sulfinate, also reacted cleanly. The use of butyronitrile or benzonitrile allowed easy separation and recycling of the catalyst. 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

The stereoselective total synthesis of (+)-epiquinamide 301 has been achieved starting from the amino acid L-allysine ethylene acetal, which was converted into piperidine 298 by standard protocols. Allylation of 297 via an. V-acyliminium ion gave 298, which underwent RCM to provide 299 and the quinolizidine 300, with the wrong stereochemistry at the C-l stereocenter. This was corrected by mesylation of the alcohol, followed by Sn2 reaction with sodium azide to give 301, which, upon saponification of the methyl ester and decarboxylation through the Barton procedure followed by reduction and N-acylation, gave the desired natural product (Scheme 66) <20050L4005>. 

Schkeryantz and Pearson (59) reported a total synthesis of ( )-crinane (298) using an intramolecular azide-alkene cycloaddition (Scheme 9.59). The allylic acetate 294 was first subjected to an Ireland-Claisen rearrangement followed by reduction to give alcohol 295, which was then converted into the azide 296 using Mitsunobu conditions. Intramolecular cycloaddition of the azide 296 in refluxing toluene followed by extrusion of nitrogen gave the imine 297 in quantitative yield. On reduction with sodium cyanoborohydride and subsequent reaction with... 

The reaction of alkenes with iodosobenzene in acetic acid in the presence of sodium azide offers a simple and high yield route to 1,2-diazides (Table 3)76. a-Azido ketones are side products or the exclusive product from the reaction with conjugated alkenes. Allylic azides or oxonitriles, resulting from oxidative cleavage of the C-C double bond, are alternatively obtained from trisubstituted steroid alkenes77. 

The alkylation reaction in a two-phase system was also extended to various heteronucleophiles [11]. Secondary amines (morpholine, benzyhnethylamine, etc.) as well as primary amines (n-butylamine, 2,2-diethylpropargylamine, cyclohexyl-amine, a-methylbenzylamine, etc.) react for example with ( )-cinnamyl acetate to give only the monoaUylated product in quite good yields [Eq. (2)]. The water-soluble nucleophiles sodium azide and sodium p-toluene sulfinate react also under these conditions, giving the corresponding aUyl azide and allyl p-toluene sulfone in 92 and 95% yield, respectively. 

The reaction was extensively stndied for cinnamyl esters (acetate and carbonate) as allylic snbstrates, with some examples given for allyl acetate and its homologues, and a wide range of nncleophiles inclnding N-nucleophiles (primary and secondary amines, hydroxylamine and its derivatives, and sodium azide), C-nucleophiles (malonates, ethyl acetoacetate, acetylacetone, sodium tetraphenylborate), and S-nucleophile sodium p-toluenesuhinate. 

Both alkyl and alkenyl amino acids can be prepared by this approach. A common method for introducing the halide into an alkene-bearing molecule is illustrated by the reaction of -pent-2-enoic acid with N-bromosuccinimide to form 1.12. Subsequent treatment with ammonia led to displacement of the bromine moiety to give 4-aminopent-2-enoic acid (J.I3). An alternative method reacted 1.12 with sodium azide and then reduced the azide with zinc and acetic acid (see section l.l.B.iv). Allylic halogenation in systems such as 1.12 are well known. 

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