Protected hydrazines

The second route was applied to the preparation of the tctrahydropyrido[ 1, Z-d 1,2,4 tria/incdione 142 by reaction of ethyl piperidinecarboxylate 140 with protected hydrazines 139 via intermediate 141 (Scheme 15) <2003SC1011>. 

Figure 1.110 The reaction of SANH with an amine-containing molecule results in an amide bond derivative that terminates in a protected hydrazine group. Reaction with an aldehyde-containing molecule results in release of the acetone-protecting group and formation of a stable hydrazone bond.

An addition to the literature on the arylation of protected hydrazines was recently contributed by Skerlj et al. [186]. In addition to the reactions of halopyridines with tert-butyl carbazate (H2NNHBoc) discussed in Section 4.3.2.3, these authors have reported the reaction of electron-deficient aryl bromides with this substrate. Reactions occurred when using DPPF or the ferrocenyl 11 as the ligand along with CS2CO3 as the base at temperatures of 100-110 °C. 

The most general method to synthesize 2,5-disubstituted N-aminopyrroles consists of a modified Paal-Knorr condensation [20] starting from 1,4-diketones and a mono-protected hydrazine (Scheme 3.2). 

Paal-Knorr condensation of these 1,4-diketones with protected hydrazines gives access to the corresponding N-protected N-aminopyrroles 1-8 in a simple proce-... 

The cis- and /ra/i5-l,3,4-oxadiazine-5-carboxylates (311 71%) and (312 57%) are prepared by ring-closure of the erythro- and threo-homers of the diBOC protected hydrazine (310 R = Bu PhjSiO) with 2-methoxypropene <89TL5507>. The more stable /ra i-isomer (312) is also available in 75% yield by base-mediated equilibration of the cw-isomer (311). 

Whatever the "real" reasons for this peculiar behavior, interesting papers centering on the synthesis of piz/A-piz containing natural products had appeared in the chemical literature by this time (1995), notably from the laboratories of U. Schmidt,but also of C. Shin and K. Hale. All these chemists had encountered serious difficulties during the acylation of unsaturated piperazic acids and their precursors. In particular, Schmidt had discovered that only N-Cbz-valinyl chloride is sufficiently reactive to acylate a terminally protected hydrazine very similar to 88. Furthermore, Olson and Rebert had determined earlier that serinylation of piperazic acids and of its precursors by any of the common methods fails. All we could do is to confirm this conclusion even cyclic A-carboxy anhydrides (NCA s) are impotent vis-a-vis 87-88. 

Aryl hydrazines. The reagent reacts with aryl iodides at 135-140° (6 hr.) to form the protected hydrazine (2), which is hydrolyzed by acid to the hydrazine (3). 

Isocyanoacrylates are proving to be versatile intermediates they react with amines to give imidazoles, with thiols to give thiazoles, with protected hydrazine to give 2-aminoimidazoles (illustrated) and with O-benzylhydroxylamine to give 1-benzyloxyimidazoles. ... 

It has been reported that A -allyloxycarbonyl-protected hydrazines, including (90), react with a palladium(O) catalyst and Bu"3SnH to give versatile intermediate tin carbamates (91) that can be converted either into the corresponding deprotected or acylated hydrazines (Equation (17)) <91TL6629>. 

Bexrud and Tautens used chiral NFlC-based bis-carbonyl compound 54 in the asymmetric hydroarylation of bicyclic Ai-Boc protected hydrazines with arylbor-onic acids (Scheme 10.3), and observed good yields (up to 86%) and excellent ee values (up to 93%) [32]. Noteworthy, no p-nitrogen-catalyzed ring-opening of the diazabicycles was observed. 

Scheme 10.3 Hydroarylation of bicyclic N-Boc protected hydrazines catalyzed by 54.

The final step in the construction of the dumbbell-shaped compound 7 involved a Fischer indole synthesis between the protected hydrazine 5 and the ketal 6, which, on treatment with acid Scheme 4), formed the indole ring system and the dumbbellshaped compound 7 in 51% yield. Low temperature NMR spectroscopy on the rotaxane 8.4PF6 in CD3CN showed that in fact the hydroquinol ring was occupied by the tetracationic cyclophane in a ratio of 100 0 This outcome is probably a consequence of steric outweighing electronic factors, leaving the indole to "solvate" the exterior of the tetracationic cyclophane. The quite decisive preference for this rotaxane... 

In the first step, Fmoc (9-fluorenylmethoxycarbonyl)-protected dithiocarbazate resin 43 was prepared by a three-component reaction of Merrifield resin 1 and carbon disulfide with Fmoc-protected hydrazine in the presence of sodium hydride in DMF at room temperature. Deprotection of the Fmoc group of resin 43 with 5% piperidine produced the corresponding free dithiocarbazate resin 42." In this step, the use of 5% piperidine was essential because a higher concentration caused loss of the desired substrate from resin 43. In addition, we have developed a more convenient synthetic route to the resin 42, compared to the previous report using hydrazine monohydrate and carbon disulfide with potassium hydroxide in ethanol solvent. Under these reaction conditions, we obtained the polymer-bound dithiocarbazate 42 without the Fmoc protection step of the hydrazine. 

Syntheses of iV-amino derivatives of various heteroaromatic systems have utilized protected hydrazines. Sometimes simple acylation gives sufficient protection, as in the synthesis of the 1-aminobenzimidazoles (51) from o-nitrophenylhydrazine [273]. 1-Acetamidobenzotriazole has been obtained in a similar... 

The hydrohydrazination represented a general solution for the amination of alkenes, but the protected hydrazines obtained are sometimes difficult to transform to the free amines. At this point, we turned to sulfonyl azides as nitrogen sources, based on then-capacity to react both with enolates and carbon-centered radicals. Mechanistic investigations of the hydrohydrazination reaction had suggested a radical character for the formed organocobalt intermediate. " We were pleased to see that the Cobalt-catalyst 4 was able to promote the hydroazidation of 4-phenylbut-l-ene (3) with ethanesulfonyl azide (7), giving the product derived from the formal Markovnikov addition of hydrazoic acid onto the C-C double bond exclusively, albeit in moderate yields (50%). 

A highly regioselective protocol was reported that delivered numerous 3,4-disubstituted indole derivatives with excellent yields by hydrazine-directed Rh-catalyzed C-H activation, in which the protected hydrazine acts as a directing group and as an internal oxidant (Eq. (5.14)) [11a]. The reaction was promoted by an acetic acid additive. Similarly, a Rh(IIl)-catalyzed reaction of an arylhydrazine salt, a diethyl ketone, and an alkyne to synthesize a 3,4-disubstituted indole was also reported by our group. The reaction proceeds by in situ condensation of an arylhydrazine with diethyl ketone to form an arylhydrazone intermediate (Eq. (5.15)) [11b]. 

Two other Cu-catalyzed reactions have been reported for preparing 2-aryl-2//-indazoles 114 (Scheme 40) [76] and 1-substituted indazolones 116 (Scheme 41) [77]. The first one started from protected hydrazines 112, which underwent intramolecular amidation and subsequent deacylation and oxidation to afford 114 with moderate yields. In this case, if base was switched from K2CO3 to CS2CO3, no ligand was required. The secondary one using amides 115 as substrates, which were catalyzed by CuI/L-proline to provide 116 with good yields. 

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