1,2-hydrazino alcohols

Pentamethyleneoxaziridine (6) also acts as an aminating agent, giving quite good yield of aziridines (Scheme 2). > Remarkably, none of the corresponding epoxide was reported in this reaction. Cyclohexene yields instead the hydrazino alcohol (8), probably via the V-aminoaziridine (7). In view of the recent use of chiral oxaziridines for chiral oxidations, it will be interesting to see whether chiral aziridination is possible when chiral V-unsubstituted oxaziridines become available. ... 

A two-step hydrolysis of crude 2 with trifluoroacetic acid and lithium hydroxide gives the optically pure a-hydrazino acids 3 (ee >98 %). Reduction with hydrogen on platinum(II) oxide reduces 3 to the a-amino acids 4 in high yields. Alternatively, 2 can also be reduced with metal hydrides (LiAIH4/Et20) to, V-inethylcphedrinc and /i-hydrazino alcohols 5. After transformation into the Mosher ester [with (- )-(S)-methoxy-4-(tri fluoromcthyljphenylacctyl chloride], 5 (R = CH3) shows a diastereomeric ratio d.r. [(2,S,2, S )/(2,S, 2 7f)] >95 5. 

Thus, this method is useful for the preparation of a-hydrazino and a-amino acids of R as well as S configuration, and of /5-hydrazino alcohols. 

Trepanier DL, Wagner ER, Harris G et al (1966) 1,4,5,6-Tetrahydro-as-triazines I. Sulfuric acid catalyzed condensation of nitriles and hydrazino alcohols. J Med Chem 9 881-891... 

The simplest derivatives to prepare are the 1,1,1-trialkylhydrazinium salts 526,527 reaction of hydrazine hydrate with chlorohydrins in an alkaline medium is also relatively smooth it gives hydrazino alcohols.528... 

With hydrazine hydrate substituted oxiranes give hydrazino alcohols,1113 and with sodium azide give azido alcohols,1114 in both cases in good yields. 

Oxazolo[2,3-fe]oxazoles (191 R = CF3, n-C7F,5) have been prepared by acid-catalyzed dehydration of A,A-bis(hydroxyalkyl)amides <82JFC(2l)359>. The imidazo[l,5-6f]imidazole (193) was prepared by reaction of aminoacetonitrile with excess trimethylorthoformate in the presence of catalytic amounts of formic acid <84JOCl2i2>. The reaction is believed to involve the initial formation of the imidate (192) which reacts successively with aminoacetonitrile and the ortho-ester to give the observed product. Pyrazolo[5,l-Z>]oxazoles (198) have been synthesized by reaction of hydrazino alcohols (195) with the Michael adduct (194), prepared from A-isobutylidene-r-butylamine and dimethyl-methoxymethylene malonate <93JHC1529>. The reaction is believed to involve cyclization of the intermediate hydrazones (196) to give pyrazoles (197), which subsequently cyclize to the bicyclic system with loss of dimethyl malonate. 

Hydrazino alcohols 296 react with ethyl benzimidate to form pyrrolo[l,2-r4[l,3,4]oxadiazine 298a or pyrido[l,2-4 -... 

Oxadiazinan-2-ones 300 are obtained from norephedrine in good yield via N-alkylation, nitrosation, reduction, and cyclization <2002JHC823, 1996JME3938>. The nitroso compounds 299 are reduced with lithium aluminium hydride and the intermediate hydrazine alcohols cyclized with carbonyldiimidazole to afford compounds 300 (Scheme 37). Similarly, l,3,4-oxadiazinan-2-one derivatives 302 are obtained by reaction of hydrazino alcohols 301 with diethylcarbonate and sodium hydride (Equation 50) <2004SC835>. 

Aldehydes 4-Amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald reagent) Aldehydes yield violet chromatogram zones on a whitish-yellow background. Some alcohols form yellow to orange-colored chromatogram zones. [2]... 

The enhanced reactivity of 5-halogeno-l,2,4-thiadiazoles over 3-halogeno-l,2,4-thiadiazoles has been mentioned before (see Section 5.08.7.1). Nucleophilic substitution at this center is a common route to other 1,2,4-thiadiazoles, including 5-hydroxy, alkoxy, mercapto, alkylthio, amino, sulfonamido, hydrazino, hydroxylamino, and azido derivatives. Halogens in the 3-position of 1,2,4-thiadiazoles are inert toward most nucleophilic reagents, but displacement of the 3-halogen atom can be achieved by reaction with sodium alkoxide in the appropriate alcohol <1996CHEC-II(4)307>. 

A hydroboration-oxidation sequence has been described for the desymmetrization of bicyclic hydrazino-alkenes. The use of BDPP as a chiral ligand on Rh provides the desired alcohol in 84% ee, following oxidation of the hydroborated... 

The substance is prepared by treating the tetrammino-derivative with 50 per cent, hydrazine hydrate on a water-bath ammonia is copiously evolved and the hydrazino-derivative is precipitated. The precipitate is blue in colour, but the last of the precipitate is almost colourless. After washing with alcohol and ether it is obtained as a reddish-violet powder which is insoluble in water. It is more difficult to decompose with hot water than the corresponding cobaltous compound. 

The aldehyde or ketone can now desorb, leading to the initial copper(I) hydrazide complex 13 which re-enters the catalytic cycle. The replacement of DEAD-H2 12 by DEAD 19 can be easily understood when considering this catalytic cycle. Indeed, several entries to the main catalytic cycle are possible, either via the hydrazino copper species 13 or via the direct formation of the ternary loaded complex 18 from the azo-derivative 19, Phen CuCl 3 and the alcohol 1. The key-role played by the hydrazine or azo compounds can also be readily appreciated when considering the proposed mechanistic rationale. The hydrazide, not only helps in reducing the copper(II) salt to the copper(I) state but, by virtue of its easy passage into the azo derivative, it also acts as a hydrogen acceptor, allowing the efficient oxidation of the alcohol into the carbonyl compound. 

Classical methods for removal of the chiral oxazolidinone moiety such as benzyl alcohol transesterification, caused some epimerization at the newly aminated center. The use of anhydrous LiSH (1 equiv., THF, 20 °C, 10 min) was successful and the cleavage occurred without sensible epimerisation. Treatment of the resulting reaction mixture with THF/CH3C03H (1 1 mixture, 40% in H20) gave the carboxylic acids 44 in 76-85 % yields. Compounds 44 were hydrogenolyzed under classical conditions (H2, Pd/C) to the free a-hydrazino acids which were converted to the a-amino acids 45 by subsequent cleavage of the N-N bond in the presence of Ra-ney-Ni (500 psi, 10% aqueous AcOH) with 80-95 % yield (Scheme 23). 

Enol Amination. The Cu[(S,5)-t-Bu-box] (OTf)2 complex was found to be optimal for promoting the enantioselective conjugated addition of enolsilanes to azodicarboxylate derivatives (eq 13). This methodology provides an enantioselective catalytic route to differentially protected ot-hydrazino carbonyl compounds. Isomerically pure enolsilanes of aryl ketones, acylpyrroles, and thioesters add to the azo-imide in greater than 95% ee. The use of an alcohol additive was critical to achieve catalyst turnover. Amination of cyclic enolsilanes was also possible. For example, the enolsilane of 2-methylindanone provides the adduct containing a tetrasubstituted stereogenic center in 96% ee and high yield. Acyclic (Z)-enolsilanes react in the presence of a protic additive with enantioselection up to 99%. ... 

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