Hydrazones, unsaturated

Unsaturated hydrazones, unsaturated diazonium salts or hydrazones of 2,3,5-triketones can be used as suitable precursors for the formation of pyridazines in this type of cyclization reaction. As shown in Scheme 61, pyridazines are obtainable in a single step by thermal cyclization of the tricyanohydrazone (139), prepared from cyanoacetone phenylhydrazone and tetracyanoethylene (76CB1787). Similarly, in an attempted Fischer indole synthesis the hydrazone of the cyano compound (140) was transformed into a pyridazine (Scheme 61)... 

Scheme 2.23 Aziridination of aji-unsaturated hydrazones with vinylmagnesium bromide.

Double intramolecular /zcfcro-Diels-Alder reaction of 1,3-diynil-bis-a,)S-unsaturated hydrazones 139 and 140 is a good example of a thermal multiple Diels-Alder reaction and is a particularly attractive route to annelated pyridines [123]. The initial cycloadduct readily aromatizes by the loss of dimethylamine (Scheme 2.52) under thermal reaction conditions. 

Aldehydes 2,4-Dinitrophenyl- hydrazine Formation of colored hydrazones or osazones. It is possible to distinguish between saturated and unsaturated hydrazones using potassium hexacyano-ferrate(III) [5]. [3,4]... 

Apart from cydopentadiene 309a, furan [151, 165, 321-323, 327, 329] and pyrrole derivatives [158, 325] 309b and 309c, respectively, are also often used as dienes. Recently, the synthetic applications of furan Diels-Alder chemistry were reviewed comprehensively [330]. In the case of a,/3-unsaturated hydrazones 312, isomerization and elimination of dimethylamine convert the Diels-Alder products 314, which... 

Treatment of a,/l-unsaturated hydrazones 100 with sulfur monochloride gave 3-imino-l,2-dithioles 101 in low yields (1985ZC400 Scheme 50). 

Double intramolecular Diels-Alder reactions of a,/3-unsaturated hydrazones have been used to prepare 2,2 bipyridines (Scheme 55) <1999CC793, 2001J(P1)2183>. 

The pioneer work on this subject using simple 1-azadienes is due to Ghosez et al. (82TL3261 85JHC69) they succeeded in reacting 1-azadienes as 47r-electron components in Diels-Alder cycloadditions. Thus, l-dimethylamino-3-methyl-l-azabuta-l,3-diene (a,/3-unsaturated hydrazone) 54 did undergo [4 + 2] cycloaddition to typical electron-poor dienophiles, e.g., methyl acrylate, dimethyl fumarate, acrylonitrile, maleic anhydride, and naphthoquinone, producing pyridine derivatives 55-57 (Scheme 14). 

In the absence of a Lewis acid promoter, the 2 + 3-reaction between p-quinone monoimide and azadienes, e.g. a,-unsaturated hydrazones yielded 2,3-dihydroben-zofurans in moderate to excellent yields when the dienophile was maintained at low concentration.43... 

Bicyclization of unsaturated imines.2 Unsaturated hydrazones, particularly N,N-dimethylhydrazones, undergo bicyclization when treated with 1 (1.35 equiv.) to cis-cycloalky lhy drazides. 

The synthesis of L-daunosamine began with the condensation of trans-crotonaldehyde (56) with dibenzylhydrazine (Scheme 17). Sharpless asymmetric dihydroxylation of the resulting ( )-a, (3-unsaturated hydrazone 57 afforded the syn-diol 58 (70% yield, 89% ee by HPLC), and silylation with chlorodimethyl-vinylsilane then provided the radical cyclization precursor 59 in 98% yield. In the key step, exposure to thiyl radicals generated from PhSH and AIBN led to radical cyclization of dibenzylhydrazone 59. The unstable cyclic intermediate was then directly treated with fluoride to afford vinyl adduct 60 in 77% yield (dr 91 9, H NMR). In control experiments with corresponding monosilyl derivatives, the (3-O-silyl... 

The anion formed on nucleophilic attack of the hydrazine stabilizes by fluoride and subsequent HF elimination to give an o ,/3-unsaturated hydrazone, which undergoes an electrocyclic ring closure with HF elimination to yield 5-fluoro-4-trifluoromethylpyrazoles. The single fluorine bonded to C(5) can be exchanged by a wide variety of nucleophiles (88S194 90BAU2338). 

To achieve this goal, (—)-carvone was transformed into the dimethylhydrazone, and the unsaturated hydrazone was deprotonated by EDA (Scheme 37). Due to complexation of the lithium ion with nitrogen, 3,3-dimethoxypropyl bromide was used to alkylate the a-position (202). A 3 2 mixture of the two possible stereoisomers 332 and 333 was obtained. The authors claimed that the ketone was... 

The investigation of the Diels-Alder reaction of 2-substituted-a,/5-unsaturated hydrazones in a concentrated solution of LiNTf2 in MeCN revealed a spectacular rate increase when the reaction of 80 with A-phenylmaleimide (81) was run in this media (2.5 M LiNTf2-MeCN) (Sch. 40). These conditions also enable cycloadditions to be performed with less reactive dienophiles such as dimethyl fumarate or malate such cycloadditions result in stereospecific cyclizations [90]. 

The mild deprotection of acetal 15 with CUSO4 in acetone was accomplished in high yield [12]. The mildness of copper Lewis acids for the hydrolysis of hydra-zones [13] is advantageous for acid-sensitive substrates (Sch. 5). The /3,a-unsaturated hydrazone 17 was effectively hydrolyzed without conjugation of the double bond to afford 18 in good yield (Sch. 5) [14]. SAMP-Hydrazones can be hydrolyzed without racemization [15]. The two-step alkylation and hydrolysis of 19 provided 20 in 84 % overall yield and 94 % ee. 

The formation of epoxy ketones from sterically crowded enones is often difficult. Avoiding the epoxi-dation step, fragmentation to give the alkynone (137 Scheme 47) occurs on treatment of the unsaturated hydrazones (145) (from 135) with an excess of NBS in methanol. Ohloff and Buchi used this sequence for a further synAesis of exaJtone (118) and muscone (119). 

Cyclic a,p-unsaturated N, V-dimethylhydrazones may be monoalkylated cleanly at the a- or a -posi-tion depending upon the conditions of formation of the metallated unsaturated hydrazone. By using (i) less reactive bases such as sodium hydride (ii) additives such as HMPA and/or (iii) allowing the metallated hydrazone to stand for a period of time before the alkylating agent is added, a-alkylations via the... 

Bushby, N.. Moody, C.J., Riddick, D.A., and Waldron, I.R., Double intramolecular Diels-Alder reaction of a,P-unsaturated hydrazones. A new route to 2,2 -bipyridines, 7. Chem. Soc., Chem. Commun., 793, 1999. 

In attempts to prepare the 2-benzyl-2-phenylhydrazone (29) of 3,5-di-O-benzoyl-2-deoxy-n-eryribose derivative), the unsaturated hydrazone (30) was obtained. ... 

In most cases the regiochemistry of the Shapiro reaction is controlled by steric factors, with the second metalation occurring at the less-substituted a-carbon atom of the hydrazone.2 For example, a-methyl ketone 10 was transformed to disubstituted alkene 11 in 69% yield as a single regioisomer via conversion to a tosylhydrazone followed by treatment with -BuLi. However, the regiochemical outcome of Shapiro reactions involving a,p-unsaturated hydrazones is difficult to predict in the absence of data obtained from reactions of structurally related substrates, as the second metalation can occur at either the a - or y-position. 

S-Unsaturated hydrazones such as (12) have been shown to behave as 1 -aza-1, 3-dienes in Diels-Alder addition reactions with a range of dienophiles such as maleic anhydride (Scheme 2). The dimethylamino substituent in the cycloadducts (e.g. 13) may be cleaved by treatment with zinc and acetic acid, but no conditions have so far been found to cleave the N-N bond without reducing the C-C double bond 5-Nitropyrimidine undergoes inverse Diels-Alder cycloaddition with electron-rich dienophiles such as enamines and ketene N,N- and 0,0-acetals (Scheme 3). ... 

In efforts to increase the reactivity of simple 1-aza-1,3-butadienes toward typical electron-deficient dienophiles, Ghosez and co-workers found that the a,/3-unsaturated hydrazone 1 behaves as a well-defined electron-rich diene in regioselective, normal (HOMOd,ene controlled) Diels-Alder reactions with a number of representative dienophiles. Reductive cleavage of the nitrogen-nitrogen bond concurrent with reduction of the carbon-carbon double bond has provided substituted piperidines, and aro-matization with elimination of dimethylamine has provided substituted pyridines (Scheme 9-1). Similar reactions of simple or functionalized a, -unsaturated oximes failed to provide an observable [4 -t- 2] cycloaddition. It remains to be determined whether this process is general for a,/3-unsaturated hydrazones capable of tautomerization. 

With an a,p-unsaturated hydrazone, addition of a nucleophile can lead to a new alkene, in which the double bond has migrated to the position formerly occupied... 

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