Conjugate addition azides

Acrolein (H2C=CHCH=0) undergoes conjugate addition with sodium azide in aqueous solution to give N3CH2CH2CH=0 Propanal is not an a 3 unsaturated carbonyl compound and cannot undergo conjugate addition... 

Conjugate addition of azide ion to dihydropyran-2,5-diones affords the 3-amino derivative <96SL341>, whilst reaction with bisnucleophiles provides a route to piperazines, thiazines and diazepines <96JHC703>. 

Addition of azide ion to conjugated systems can be carried out by using NaN3 and acetic acid in water (Eq. 10.18).38 Some reactions were very rapid while others took 1 to 3 days to complete. Lewis base was found to catalyze such conjugate additions of azide ion to cyclic enones in water.39... 

Morpholine, pyrrolidine and sodium azide can also be also used as nucleophiles in the synthesis of 3-substitututed A3-cephems 515 via the conjugate addition of the 2,3-allenoate moiety in 513 [233]. 

Sodium azide also adds to olefins of this t3rpe to give w-triazoles in fairly good yields. A mechanism involving nucleophilic displacement of the substituent X by azide, followed by cyclization of the vinyl azide in the presence of azide ions, has been suggested. An alternative mechanism involves conjugate addition of azide to the double bond, cyclization of the resulting anion, and aromatization. 

Conjugate addition to 1 proceeded across the open face of the bicyclic system to give an enolate, condensation of which with the enantiomerically-pure aldehyde 8 gave the enone 9. Conjugate reduction of the enone also removed the benzyl ether, to give the alcohol. Conversion of the alcohol to the azide gave 10. Ozonolysis followed by selective reduction then gave 2. 

Miller and co-workers, as part of their program in connection to the development of polypeptides as practical and readily modular chiral catalysts and new screening protocols for combinatorial synthesis, have been able to achieve efficient catalytic enantioselective conjugate additions of azides to acyclic enones [15]. As the example in Eq. (5) illustrates, the resulting 3-azidocarbonyls can be easily modified to afford N-containing heterocycles. 

The predominant formation of five-membered carbocydes or heterocycles 122 (Scheme 50) via a sequential conjugate addition-carbene insertion pathway is generally observed in the reactions of the appropriate alkynyliodonium salts 119 (R = long alkyl chain or other group with C-H bond available at C5) with various relatively hard nucleophiles. Typical nucleophiles used to initiate these selective cyclizations are enolate, azide, sulfinate, tosylamide, thioamide and some other anions. 

Conjugate addition of hydride or piperidine to 3-methyleneazetidin-2-one 111 affords the products 112. 4-(Iodomethyl)azetidin-2-one undergoes nucleophilic substitution by sodium azide in DMF to give the azido compound. 

J-Mercurio nitro compounds have been used to prepare nitroalkenes, which undergo conjugate addition with various nucleophiles. For example, the addition of ammonia or sodium azide/hy-drazoic acid mixture to 1-nitrocyclohexene allows the multistep preparation of either cis- or trans-1,2-cyclohexanediamine14 ... 

In a reaction quite similar to the aforementioned addition-elimination reactions, conjugated vinyl azides have been obtained from certain terminally unsubstituted allenic esters (equation 9)... 

The tetrazole synthesis was done with azide and acetic acid and base-catalysed conjugate addition followed by treatment with SOCl2, to make the acid chloride, and piperidine completed the synthesis.13... 

Malonate and related activated methylene compounds have also been used as the nucleophile in conjugate addition/Michael reactions. Taylor and co-workers have developed a new methodology that utilizes (salen)aluminum complexes such as 43 as a catalyst to effect the enantioselective conjugate addition to a,p-unsaturated ketones by a variety of nucleophiles.25 For example, nitriles, nitroalkanes, hydrazoic acids, and azides have found utility in this reaction. Additionally, cyanoacetate (42) has been demonstrated to undergo a highly enantioselective conjugate addition to 41. The Krapcho decarboxylation is then necessary to produce cyanoketone 44, an intermediate in the synthesis of enantioenriched 2,4-cw-di substituted piperidine 45. 

In Magnus studies of jff-azidonation of triisopropylsilyl (TIPS) enol ethers, it was found that addition of TEMPO had a profound effect on the reaction pathway [82]. When TIPS protected enol ether 49 was allowed to react with PhIO and TMSN3 in the absence of TEMPO, compound 51 was obtained as the major product however, in the presence of catalytic TEMPO, compound 53 was obtained (Scheme 27). The formation of product 51 is postulated to occur via conjugate addition of azide anion to an enonium cation intermediate 50, whereas compound 53 is proposed to form via the formation of azide radical, which adds to the silyl enol ether double bond to form intermediate 52. 

A general method for the introduction of different functionality into position 5 of cholestanes has been developed. The conjugate addition of organic and inorganic nucleophiles to 6-nitrosocholesteryl acetate (325), generated in situ from 3j8-acetoxy-5-chloro-6-hydroxyimino-5a-cholestane (324) afforded the 5oc-substituted 6-oximes (326). The nucleophiles which have been used include ethanediol, ethanol, methylamine, ammonia, nitrite, cyanide, thiocyanate, and azide. 

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