Carbanion reductive method

Phosphole sulfides are frequently stable, unlike oxides which rapidly dimerize, and can be used as precursors of phospholes by simple reduction methods. In another approach <80NJC683>, this stability was taken advantage of for the introduction of the carboxylate group on the 3,4-dimethyl-phosphole ring (Scheme 83). The sulfide forms a carbanion (270) which can be quenched with diethyl oxalate to form a phosphole sulfide 2-carboxylate. This was converted to the phosphole by removing the sulfur with a more nucleophilic phosphine (tri- -butylphosphine or tris-(2-cyano-ethyOphosphine). The phosphole-2-carboxylates prepared this way ((271) and (272)) were significantly more stable than the 3-carboxylates and could be stored at room temperature. 3,4-Dimethyl substitution is well known to increase the stability of phospholes, and at present it is unknown if this substitution pattern or the position of the carboxylate is responsible for the increased stability. 

Ethyl stearate added with stirring at 0° under Ng to 2 equivalents of a ca. 1 M soln. of methylsulfingl carbanion (prepn. s. Synth. Meth. 17, 895) in dimethyl sulfoxide-tetrahydrofuran, allowed to warm to room temp, over 30 min., then water added j6-ketosulfoxide (Y > 98%) stirred and refluxed 60-90 min. with Al-amalgam in tetrahydrofuran containing 10% water n-heptadecyl methyl ketone (Y > 98%). F. e. also ketones from -ketosulfones and )6-ketosulfonic acid amides by the same reduction method, s. E. J. Gorey and M. Chaykovsky, Am. Soc. 86, 1639 (1964). 

The a-sulfonyl carbanions can be trapped with a variety of electrophiles19. The method provides a synthetically useful synthon for a propylene 1,3-dipole. Reductive cleavage of the sulfone 28 thus prepared, with lithium phenanthrenide in THF, furnishes bicyclooctane 29 (equation 19)16. 

Control of the stoichiometry of the reagents allows also for the preparation of fairly pure three, four and five-arm stars by this method. This conclusion was confirmed [50], Addition of THF complicates the coupling reaction between carbanions and C60. First a two electron reduction of C60 is observed. This is... 

Reactive donors can be generated ca-thodically by reductive cleavage of hahdes to carbanions or by reduction of double bonds to radical anions. Using these methods, two acceptors can be dimerized in one step by reductive Umpolung , for example, two molecules of acrylonitrile to adipodini-trile - a reaction, which normally needs two or more steps. 

Tlte reduction potential for an alkyl or benzyl radical, relative to that of the carbon-halogen bond from which it is derived, is important in determining the isolated products. Products are derived either by radical or by carbanion chemistry. The half-wave potential for the second polarographic wave of alkyl halides is connected with reduction of the radical. Sophisticated methods have been devised for deducing radical reduction potentials in cases where (his second wave is not seen. Values are collected in Table 4.4. 

Cyclization of the product (27-2) under Friedel-Crafts conditions gives the desired indolinone (27-3). Reaction of the carbanion obtained on treatment of that with 3-chloropropyldimethylamine then gives the alkylation product (27-4). It should be noted that, in spite of this extra step, the scheme is greatly simplified by starting with the very readily available tertiary amine. The superfluous methyl group is then removed by reaction of (27-4) with ethyl chloroformate in the current version of the Von Braun reaction. There is thus obtained amedalin (27-5). Reduction of the amine by any of several methods, for example diborane, leads to the antidepressant daledalin (27-6) [28]. 

Johnson in 1993 described an approach to racemic p-amyrin involving application of a biomimctic polyene cyclization.7 In the same year Corey accomplished the enantioseleetive synthesis of compound 4. a key intermediate that opened the way to stereoselective preparation of compounds I, 2. and 3 8 A key step in the synthesis of P-amyrin (1) was the introduction of chiral oxazaboroli-dines for enantioseleetive carbonyl reduction. Ba ed on these methods, generation of an enantiomerically pure epoxide and its stereoselective cationic cyclization led to the pentacyclic system of structure 1 Diastereoselective cyclopropanation and an intramolecular protonation of a carbanion represent other interesting steps in this total synthesis. 

Another methods for the electrochemical formation of the active carbanion is the cathodic reduction of iminium salts. When an iminium salt is reduced in the presence of a suitable alkylating agent, an alkyl group is introduced to the carbon atom of the imine. Some isoquinoline and indole type alkaloids are synthesized by using this substitution method as exemplified bellow by the synthesis of laudanosine 51 37>. 

Three methods of Co-C bond cleavage have been proposed to occur in cobalamins (Scheme 15). Heat or photochemical irradiation can induce homolysis of the Co-C bond with a consequent one-electron reduction of cobalt. Nucleophilic attack on the methyl group can occur, resulting in reduction of Co to Co. Electrophilic attack (e.g. mercmy methylation) can also occur, where the methyl group is transferred as a carbanion. " ... 

The second is in situ, where generation of the EGB by reduction of the PB takes place in the presence of reactant(s). The advantage of this mode of operation is that the EGB can be short-lived, and the applied current can control the amount of base present at any time. The major disadvantage is that the PB must be more easily reduced than the reactant(s). This method is the one most commonly used. An early example of a radical anion EGB is shown in Scheme 3. The method has also frequently been used to generate carbanion EGBs from alkyl or aryl halides as illustrated schematically in Scheme 2. 

In 1972, Tsuchihashi disclosed that the carbanion (28 Ar = p-tolyl), generated from (/ )-methyl p-tolyl sulfoxide with lithium diethylamide, adds to benzaldehyde or a-tetialone to give an adduct (29) in a dia-stereomeric ratio of 50 50 or 64 36, respectively. Additions of this carbanion to various unsymmetrical ketones are also reported to be poorly diastereoselective (for example, EtCOMe 50 50, Bu COMe 55 45, Bu COPh 70 30). Note that in the case of Ar = 2-pyridyl a chiral sulfinyl group increases the asymmetric induction observed in the addition of the corresponding carbanion to carbonyl compounds (PhCHO 80 20, R-C9H19CHO 70 30). Since diastereomer pairs of (29) are separable, chromatographic separation followed by reductive desulfurization with Raney Ni provides a method for obtaining optically active alcohols (30 Scheme 9). 

A completely different route devised by Prelog and co-workers (14) not only afforded a new synthesis of the erythrinane skeleton but also achieved a method of introducing an oxygen function at C-3, the site of the aliphatic methoxyl in the alkaloids. The synthesis is outlined in Fig. 5. The dihydroisoquinolinium salt XXXIV was prepared by Bischler-Napieralski ring closure of the lactam XXXIII. Hydrolysis of the vinyl chloride of XXXIV gave the methyl ketone XXXV. When this salt was made alkaline, addition of the carbanion from the acidic methyl to the C=N double bond created the spiro link. Sodium borohydride reduction of XXXVI gave a mixture of epimeric alcohols. One of them had an IR-spectrum identical with that of a transformation product (XXXVII) of erysonine (If) and on resolution w ith tartaric acid its (— )-enantiomer proved to be identical with XXXVII. 

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