Propionyl chloride reduction

Although geneologically related to indoles, the dihydroindoles behave chemically rather like alkyl anilines. When diphenylamine reacts with chloro-propionyl chloride, amide 40 results this in turn readily cyclizes to oxindole 41. Sodium hydride followed by 2-chloroethyldimethylamine alkylates the 3-position (possibly through an intermediate aziridinium ion) partial demethylation is accomplished by refluxing with ethylchiorocarbonate, followed by hydrolysis of the intermediate carbamate to give indolinone 42, the antidepressant amedalin Repetition of this sequence on the chloropropyl homologue, followed by reduction of the appropriate indolinone produces dihydroindole 43, daledalin, which also has antidepressant activity. ... 

Methyl- 1,3-cyclopentanedione is a key intermediate for the total synthesis of steroids.2 A number of methods have been described for its preparation, among them the condensation of succinic acid with propionyl chloride,3 and that of succinic anhydride with 2-buten-2-ol acetate,4 both in the presence of aluminum chloride. It has also been obtained from 3-methylcyclopentane-1,2,4-trione by catalytic hydrogenation5 and Wolff-Kishner reduction 6 The base-promoted cyclization of 4-oxohexanoic acid ethyl ester and diethyl propionylsuccinate with tertiary alkoxides was first reported by Bucourt.7 The present cyclization process provides an experimentally simple route to 2-methyl-1,3-cyclopentanedione. Using the same procedure, 4-oxoheptanoic acid ethyl ester has been cyclized to give 2-ethyl-l,3-cyclopentanedione in 46% yield... 

The Ireland contribution to nonactic acid synthesis, outlined in Scheme 4.32, involves a selective silyl ketene acetal formation and Claisen rearrangement in the key step. D-Mannose (209) was readily converted in a straightforward manner to dihydrofuran 212 via 210 and 211 in 36% overall yield. Esterification of the free alcohol with propionyl chloride followed by the an enolate Claisen rearrangement afforded a mixture (89 11) of tetrahydrofuryl propionates 213 after catalytic reduction. 

Numerous examples of the Burgstahler-modifled-Rosenmund reduction have since appeared in the literature (Scheme 10). The reaction was used to prepare radiolabeled pro-pionaldehyde from the labeled propionyl chloride (22). The conditions are mild enough to prepare a variety of a,ester aldehydes from The hydrogenation... 

The chiral auxiliary is the oxazolidinone (24) derived from IS,2R) norephedrine. Acylation with propionyl chloride gives (25) and this is deprotonated to afford exclusively the internally chelated Z-enolate, which reacts with methallyl iodide from the face opposite the methyl and phenyl groups of the auxiliary. The product (26), a 97 3 mixture of diastereomers, is purified to a ratio of better than 500 1. Reductive removal of the auxiliary and careful oxidation of the primary alcohol under non-racemising conditions affords the chiral (5)-aldehyde (27). This in turn is reacted with the boron enolate of (25), which furnishes with remarkable selectivity the u aldol product (28). The reason for the choice of boron rather than lithium is to invert the facial selectivity of the reaction— the enolate is no longer constrained to be planar by internal chelation and rotates in order to place the bulky dibutyl borinyl group on the opposite side to the methyl and phenyl ... 

During the last two decades the synthesis of levofloxacin and its S-(-)-pre-cursors has been improved considerably, and new approaches have been advanced [243-255], In particular, kinetic resolution of 7,8-difluoro-2,3-dihydro-3-methyl-4H-[l,4]-benzoxazine racemate using naproxen, N-[sulphonylsubstituted]-(/ )-proline and (2S)-(6-methoxynapht-2-yl)propionyl chloride, has been advanced [256-261], The optically active (5)-isomer obtained by this method has been used for the synthesis of levofloxacin (5)-(-)-80 [256]. Also a new synthetic approach to (5)-isomer through catalytic reduction of 7,8-difluoro-3-methyl-2 (-l,4-benzoxazine with use of chiral Bronsted acids as catalyst and substituted dihydropyridine as a source of hydrogen has been described [262],... 

In continuing research, (-)- and (+)-KSU 1415 [(-)- and (+)-72] were similarly prepared by the reaction of the respective enantiomers [(-)- and ( -)-4 3] with propionyl chloride followed by reduction of the resulting enantiomeric 71 with lithium aluminum hydride in tetrahydrofuran (40) (Scheme 12). The biological evaluations of these compounds have not been reported. 

The reaction of 11 with tosyl chlorides gave imino ether (36). The reduction of 36 yielded 9-deoxo-9a-aza-9a-homo-EM A (37). The synthesis of its N-, O-acyl, and A,0-diacyl azalide derivatives, their 11, 12-cyclic carbonates, and their in vitro antimicrobial activities were studied, but 9a-N monoacyl (acetyl, propionyl) compounds exhibited in vitro activity 10 to 50 times lower than that of 37 [26]. 

---