Hydrazines, aldehyde additions preparation

An excellent synthetic method for asymmetric C—C-bond formation which gives consistently high enantioselectivity has been developed using azaenolates based on chiral hydrazones. (S)-or (/ )-2-(methoxymethyl)-1 -pyrrolidinamine (SAMP or RAMP) are chiral hydrazines, easily prepared from proline, which on reaction with various aldehydes and ketones yield optically active hydrazones. After the asymmetric 1,4-addition to a Michael acceptor, the chiral auxiliary is removed by ozonolysis to restore the ketone or aldehyde functionality. The enolates are normally prepared by deprotonation with lithium diisopropylamide. 

Alternatively, chiral hydrazones can be prepared from chiral aldehydes, e.g., 161, which underwent addition of allyltrichlorosilane in DMF to give the homoallylic hydrazine 162 with high yield and excellent diastereoselectiv-ity [76] (Scheme 25). 

The azines represent another class of organic compounds which, in principle, should be reducible to azo compounds. The method is attractive since, with the availability of anhydrous hydrazine, azines are readily prepared from a wide variety of ketones and aldehydes. Evidently, introduction of 1 gram-molecule of hydrogen into an azine molecule has only recently been accomplished (see Section 6, Procedure 8) [73], Two preparations involving the 1,4-addition of chlorine to an azine system have been carried out and are illustrated here. 

A number of aliphatic hydrazones (374) are slowly transformed into the solid hexahydro-1,2,4,5-tetrazines (375) when left at room temperature. Addition of acetic acid/acetate buffer (pH = 5.5) to the hydrazone causes almost instantaneous conversion of the hydrazone into the hexahydrotetrazine. This acceleration of the rate of dimerization suggests the intermediacy of a protonated hydrazone (376) (77TL3155, 73ACS779, 72TL949, 71AJC1859, 70TL2199,63 AG 1204). In acidic media there is an equilibrium between the hexahydrotetrazines and the hydrazones (70HCA251). The hydrazones (374) are also intermediates in the preparation of the hexahydrotetrazines from aldehydes and hydrazines. 

Chiral hydrazines, supported on Merri-field resin, were reacted with various aldehydes, affording the corresponding hydrazones. These compounds allowed stereoselective preparation of a-branched amines, through 1,2-addition of both aromatic and aliphatic nucleophiles to the C=N double bond of the hydrazones. Reductive cleavage released the desired amine from the resin. Moderate to good enantiomeric excesses (50-86%) were achieved. 

Hydrazones can be readily prepared by the addition of a hydrazine to an aldehyde or ketone. Treatment of tosyl hydrazones (or other arylsulfonyl hydrazones) with a base has been used for the preparation of alkenes. In the Bamford-Stevens reaction, a mild base, such as NaOMe or KH, is employed and promotes deprotonation of the acidic N—H proton (compare with the Eschenmoser fragmentation. Scheme 2.33). 

This reaction was first reported by Kishner in 1911. It is the preparation of cyclopropane derivatives by decomposition of pyrazolines formed from hydrazine and a,p-unsaturated ketones or aldehydes. Therefore, it is known as the Kishner reaction, Kishner decomposition, or Kishner method. In addition, this reaction has been modified to prepare pyrazoline intermediates from diazomethane and unsaturated carbonyl compounds, such as maleic and fumaric esters, resulting in an ester group in the trans position. However, when maleic anhydride or maleimide is used, the corresponding pyrazoline is formed with carbonyl groups in the cis configuration. It has been found that the stability of pyrazolines varies considerably, decomposing to cyclopropanes at different rates. Moreover, the transformation of pyrazolines into cyclopropanes can be catalyzed by a trace amount of mercuric ion. ... 

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. 

The use of 2,4,6-tri-isopropylbenzenesulphonylhydrazides (in place of the tosylhydrazide) allows milder conditions to be used for the preparation of aromatic aldehydes by the McFadyen-Stevens reaction. Addition of hydrazine hydrate and traces of cupric sulphate suppresses formation of aromatic ester and alcohol by-products. Reduction of oxazolinium salts by sodium borohydride, as part of the well known sequence for the conversion of carboxylic acids into aldehydes, can lead to ring cleavage to form amino-alcohols. It is now reported that over-reduction is much less marked if potassium tri-s-butylborohydride is used as reducing agent (Scheme 2) ... 

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