Allyl hydrazines, synthesis

Figure 22. Synthesis of allyl hydrazines through addition of cyclic allyl/enol ethers and olefins to 1,2-diazenes photocatalyzed by ZnS or CdS.

Heterocycles can be employed as precursors for the synthesis of pyrazoles. Pyrazoles can be synthesized by three-membered ring substrates. For example, allyl amines 12 and pyrazoles 13 could be obtained by hydrazinolysis of 2-ketoaziridines 11 <06TL255>. Regioselective ring opening of 3-aryl-2-benzoyl-l,l-cyclopropanedicarbonitriles 14 with hydrazine provided a new process for the synthesis of 5-aryl-3-phenylpyrazoles 15 <06JHC495>. 

During the total synthesis of the anticancer natural product OSW-1, Z. Jin and co-workers explored several approaches to prepare a crucial steroid enone precursor with high stereoselectivity. In one of the approaches, the commercially available 5-pergnen-16,17-epoxy-3 3-ol-20-one was protected with a TBS group and was subjected to the Wharton transposition. The epoxyketone was treated with hydrazine hydrate in THF/MeOH under reflux to give the expected allylic alcohol in good yield. The desired enone was obtained by the Dess-Martin oxidation of the allylic alcohol with a slight preference for the (Z)-stereoisomer. 

The synthesis of the bioactive natural product warburganal from (-)-sclareol was carried out by A.F. Barrero et al. The bicyclic allylic acetate was epoxidized and deacetylated under basic conditions. Next, the solution of the ketoepoxide in glacial acetic acid was treated with hydrazine hydrate and the resulting mixture was heated at reflux for 30 minutes to afford the bicyclic allylic did in excellent yield. 

For the more reactive allylic halides 4 a and 4 b the salt of diethyl hydrazinodicarboxylate was used as the nucleophile in preference to hydrazine.Deazetization of the resultant 4,5-dihydro-37/-pyrazoles 5 gave a mixture of alkylidenecyclopropanes 6 and 7. It should be noted that attempts to make 4-isopropylidene-4,5-dihydro-37/-pyrazole (5 b) by the more obvious route (by the reaction of diazomethane with 3-methylbuta-l,2-diene) failed. This route has been modified for the synthesis of various deuterated derivatives of 5 and used to make optically active (3/ ,57 )-3,5-dimethyl-4-methylene-4,5-dihydro-3/f-pyrazole, but all of the cyclopropanes produced from thermolysis of this compound were racemic. A similar route has also been used in the synthesis of 7,7-dimethyl-6b,7a-dihydro-7//-cycIopropa[fl]acenaph-thylene. ... 

Solid-phase synthesis by the cyclization of polymer-bound hydrazones of [1-keto esters. Jung and co-workers (99JOC1362) (Scheme 24) have reported the synthesis of pyrazol-3-one 102 from polymer-bound /1-keto ester 100 and phenyl hydrazine. In the first step, polymer-bound 3-hydroxy-2-methylidenepropionic acid 99 is derived from a Baylis-Hillman reaction between polymer-bound allylic alcohol... 

Raquin, J.F., Defieber, C., Stephenson, C.R.J., and Carreira, E.M., Asymmetric synthesis of 3,3-diarylpropanals with chiral diene-rhodium catalysts, J. Am. Chem. Soc. 127 (31), 10850, 2005. Ritter, T., Kvaerno, L., Werder, M., Hauser, H., and Carreira, E.M., Heterocyclic ring scaffolds as small-molecule cholesterol absorption inhibitors, Org. and Biomol. Chem. 3 (19), 3514, 2005. Waser, J., Gonzalez-Gomez, J.C., Nambu, H., Huber, R, and Carreira, E.M., Cobalt-catalyzed hydro-hydrazination of dienes and enynes access to allylic and propargylic hydrazides, Org. Lett. 1 (19), 4249, 2005. 

The acetoxy group was hydrolyzed using hydrazine to give (46). Nucleophilic substitution of the fluorine atom produced the tricyclic p lactam (47). A diastereoselective aza-Diels-Alder reaction was used in a synthesis of (—)-lasubine (I). Tin tetrachloride-mediated reaction of complex (48) with Danishefsky s diene afford 2,3-dihydro-4-pyridone (49) as a single diastereomer (Scheme 86). Chiral benzaldehyde imines can be allylated with high diastereoselectivity to give optically active homoallylic amines (Scheme 87). 

Reactions induced by ultrasonic irradiation of methyl 9,12-dioxostearate with hydrazines in water in the presenee of acidic alumina gave high yields of pyridazine fatty esters directly (95). The synthesis of novel piperidine- [25] and pyridine- [26] containing long-chain fatty ester derivatives has been reported starting from methyl wo-ricinoleate, 9-hydroxy-18 l(12Z) (96). Allylic amination of methyl oleate with bis(A-p-toluenesulfonyl)sulfodiimide gave a mixture of methyl ll-amino-(iV-p-toluenesulfonyl)-18 l(9 ) and methyl 8-amino-(Af-p-toluenesulfonyl)-18 l(9 ) (97). 

In 2009, Mangion et al. found that hydrazines and hydroxylamines eould be excellent nucleophiles for the Pd-catalysed allylic amination of butadiene monoepoxide in the presence of this ligand. The DYKATs afforded the corresponding amino alcohols in good yields and enantioselectivities, as shown in Scheme 2.50. The method was applicable to acyclic and heterocyclic amines, and applied towards a live-step synthesis of (f )-piperazic acid. 

Synthesis of homoallylic alcohols through the reaction of organometallic allyl compounds with carbonyl compounds is one of the most important processes in organic synthesis. Sc(OTf)3-catalyzed allylation of aldehydes with tetraallyltin to prepare homoallylic alcohols has been reported. Recently, it was revealed that the addition of acetic anhydride to the reaction mixture dramatically increases the reaction s yields to more than 90% [10]. On the other hand, in the presence of a catalytic amount of Sc(OTf)3 (l-5mol%), benzoylhydrazines reacted with tetraallyltin to give the corresponding homoallylic hydrazines, which were readily converted to homoallylic amines (Scheme 12.6) [11]. Three-component reactions of aldehydes, benzoylhydrazine, and tetraallyltin also proceeded smoothly in the presence of a catalytic amount of Sc(OTf)3. 

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