Hydrazone carbanions, reaction with

F.ii. Hydrazone Carbanions. Corey and Endersl introduced an alternative to Wittig s imine-carbanion methodology discussed in Section 9.4.F.i. Changing the imine to a hydrazone unit led to a more controllable and useful reaction. A,A-Dimethylhydrazone 313 was formed by reaction of 2-methylcyclo-hexanone and dime thy Ihydrazine. Subsequent reaction with LDA was followed by addition of methyl... 

Diastereoselectivity is also observed in reactions of carbanions derived from imines and hydrazones, when those species contain a chiral center or a chiral auxiliary (sec. 9.4.F). Asymmetric imines can be used, and chiral oxazoline derivatives have also been prepared and used in the alkylation sequence (sec. 9.3.A). Meyers showed that chiral oxazoline 478 could be alkylated to give the ethyl derivative, 479. A second alkylation generated the diastereomeric product 480, and hydrolysis provided the chiral lactone (481) in 58% yield and with a selectivity of 70% ee for the (R) enantiomer. 53 As pointed out in Section 9.4.F.ii, hydrazone carbanions can be used for alkylation or condensation reactions. In a synthesis of laurencin. Holmes -l prepared the asymmetric hydrazone 483 (prepared by Enders by reaction of cycloheptanone and the chiral hydrazine derivative called SAMP, 482-A-amino-(2S)-(methoxymethyl)pyrrolidine)- - and showed that treatment with LDA and reaction with iodomethane gave an 87% yield of the 2-ethyl derivative in >96% de. Ozonolysis cleaved the SAMP group to give (/ )-2-ethylcycloheptane (484) in 69% yield. The enantiomer of 482 is also known (it is called RAMP, A-amino-(27 )-(methoxymethyl)pyrrolidine). 

The mechanism of the reaction may involve the formation of an anion by the base B, followed by the shift of hydrogen on the hydrazone anion with simultaneous loss of nitrogen to yield a carbanion ... 

The reaction of alkyllithium reagents with acyclic and cyclic tosylhydrazones can lead to mixtures of elimination (route A) and addition (route B) products (Scheme 22). The predominant formation of the less-substituted alkene product in the former reaction (Shapiro Reaction) is a result of the strong preference for deprotonation syn to the N-tosyl group. Nucleophilic addition to the carbon-nitrogen tosyl-hydrazone double bond competes effectively wiA a-deprotonation (and alkene formation) if abstraction of the a-hydrogens is slow and excess organolithium reagent is employed. Nucleophilic substitution is consistent with an Su2 addition of alkyllithium followed by electrophilic capture of the resultant carbanion. 

A completely different approach initially involves the addition of the carbanion of ethyl 2-cyanoacetate 142 in the presence of base to the imine group of 2-naphthylsulfonyl hydrazone 147 followed by cyclization and oxidation to pyrazol-3-one 150 (02NN469) (Scheme 34). The reaction requires heating in ethanol with triethylamine and it is suggested that intermediate 148 is first produced, and then undergoes an intramolecular acyl substitution resulting in the unstable pyrazol-3-one 149. The latter is prone to oxidation by molecular oxygen and is converted to stable pyrazol-3-one 150. 

In Section 9.4.A, it was noted that there were problems with aldol-type reactions, especially with the directed aldol condensation. In particular, aldehydes with an a-hydrogen have great difficulty adding to ketones due to their propensity for self-condensation. The ability to use kinetic control conditions in enolate reactions of ketones and aldehydes often solves this problem. There are also several alternative approaches that involve the use of carbanions derived from imines and hydrazones and these can be very useful. l... 

The use of potassium <-butoxide as the base directly produced a low yield of 1-azirine contaminated with propiophenone. However, Nair has reported that azirine (37) can be prepared from hydrazone (34) in 63% yield by using the dimethylsulfinyl carbanion as the base. Even if the a-hydrogen is tertiary, this does not always ensure success of the reaction. Treatment of 38 with sodium isopropoxide... 

Reactions of Azirines.—Two groups of workers have investigated the preparation of 2H-pyrroles by the reaction of carbanions with azirines. Laurent etal. obtained azirines from the action of base on methiodides of AW-dimethyl-hydrazones the azirines could be used, without isolation, to provide overall yields of 65—70% of pyrroles, based on the quaternized hydrazones. The azirine (286 R = = Me, R" = Ph) reacted with (287 R = H or Me, R = H) in... 

The mechanism of the reduction is believed to involve deprotonation of the hydrazone to give the anion 121 (7.109). This is followed by the rate-limiting protonation at the carbon atom and deprotonation of the terminal nitrogen atom to give 122. Loss of nitrogen and protonation of the carbanion gives the product. In line with this mechanism, the polar aprotic solvent DMSO increases the rate of the reaction, and with potassium tert-butoxide in DMSO reduction can even be carried out at room temperature. 

Reaction of 2,6-dimethyl-l,4-benzoquinone with the quinomethyl carbanion derived from 2,3-dimethyl-1,4-naphthoquinone is reported to give the tricyclo-[6,3,l,0 ]dodecane derivative (749). Pyrolysis of the sodium salt of the tosyl-hydrazone of 7-cycloheptatrienylmethyl methyl ketone in diglyme at 150 C afforded (750 7%) similar pyrolysis of the tosylhydrazone salt from l-(7-cycloheptatrienyl)-ethyl methyl ketone gave (751 9 %). Both compounds are examples of the previously... 

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