Lactone hydrazones

S. E. Mangholtz and A. Vasella, Synthesis of JV-tosylglycono-1,4-lactone hydrazones as precursors of glycofuranosylidene carbenes, Helv. Chim. Acta, 78 (1995) 1020-1035. 

Instead, we turned our attention to the asymmetric alkylation of y-butyrolactone or its (o-hydroxy esters derivatives. The work by Enders and co-workers using SAMP or RAMP lactone hydrazones has shown great success with six- and seven-membered ring lactones. We decided to examine the use of this protocol in a five-membered ring analogue. 

Intramolecular substitutions mediated by Ag" " do not seem to require activated halides. For example, w-chloro amides react with AgBF4, giving products from intramolecular attack of the amide oxygen. Depending on the structure of the amide, imino lactones, imino lactonium salts, or lactone hydrazones (eq 4)" are obtained as products. Huorination of a-bromo ketones using AgBp4 has also been reported. ... 

Thus, the lithiated SAMP hydrazones of various methyl ketones on addition to 2-(aryl-methylene)- , 3-propanedionates and propanedinitriles provide, after the removal of the auxiliary, (R)-2-( l-aryl-3-oxobutyl)-1,3-propanedioates and -propanedinitriles with high enantiomeric excess (> 95%) in 50 82% yield (sec Table 6) 195,197. Using similar methods optically active (5-lactones (90% to > 96% ee) are obtained198. 

L-fhreo-2,3-Hexodiulosono-1,4-lactone (dehydro-L-ascorbic acid) 2-(p-bromophenyl)hydrazone DASCBH 37 386... 

Treatment of carboxyaldehydes 252 with hydrazine hydrate in ethanolic KOH under refluxing conditions provides an easy entry to the novel imidazo[2,l-4][l,3]thiazole fused diazepinones 253 via lactone ring opening by intramolecular nucleophilic attack of the amino group of the intermediate hydrazone which could not be isolated (Equation 31) <2006TL2811>. 

The alkylation of metalated imines, hydrazones, 4,5-dihydrooxazoles, 4,5-dihydroisoxazoles, 5,6-dihydro-4/7-1,2-oxazines and 2,5-dialkoxy-3,6-dihydropyrazines (i.e., azaenolates) is a commonly used method in asymmetric synthesis of enantiomerically enriched aldehydes, ketones, spiroacetals, amines, /J-oxo esters, carboxylic acids, lactones, 1,3-amino alcohols, /(-hydroxy ketones and amino acids. 

Neonepetalactone, 61 (Fig. 1.2.3), a bioactive compound found to be quite attractive to cats [41], was isolated in 1965 from the leaves and galls of Actinidia polygama by T. Sakan et al. and its absolute configuration was determined in 1980 [41b]. As some syntheses of the racemic mixture or ex-chiral-pool syntheses had already been reported, we realized that our SAMP/RAMP hydrazone methodology would make it possible to develop a very short asymmetric synthesis of this bioactive 8-lactone. 

Almotriptan has also been synthesized via decarboxylation of the carboxylic acid intermediate 65, but a detailed preparation of 65 was not provided in the patent literature (Scheme 22)." The patent indicates that the carboxy indole 65 was prepared according to the method of Gonzalez.°° Thus, (2-oxo-tetrahydro-3-furanyl)-glyoxylic acid ethyl ester (62) was heated in aqueous H2SO4 to give 2-oxo-5-hydroxypentanoic acid in situ, which was treated with hydrazine 59 to produce hydrazone 63. Fischer cyclization of 63 using HCl gas in DMF gave the lactone 64, which was converted to carboxylic acid 65. Decarboxylation of 65 was catalyzed by cuprous oxide in quinoline at 190 °C to afford almotriptan (5)." ... 

BC13 convert 0=0 groups of ketones, lactones, and lactams to G=S groups119 and H2S-Me3SiCl-i-Pr2NLi converts carboxylic esters to thiono esters.120 Carboxylic acids RCOOH can be converted directly to dithiocarboxylic esters RCSSR, 120a in moderate yield, with P4S, and a primary alcohol R OH.121 Thioketones can also be prepared by treatment of ketones with P4SI0,122 and from oximes or various types of hydrazone (overall conversion C=N------> C=S).123... 

Lactone NJf-dialkylhydrazones.1 These hydrazones (2) have been obtained for the first time by reaction of halohydrazides (1) with 2 equiv. of AgBF4 in THF. Cyclization of 1 with NaH results in N-(dialkylamino)lactams (3). 

A highly selective method for the preparation of optically active 3-substituted or 3, y-disubstituted-S-keto esters and related compounds is based on asymmetric Michael additions of chiral hydrazones (156), derived from (5)-l-amino-2-methoxymethylpyrrolidine (SAMP) or its enantiomer (RAMP), to unsaturated esters (154).167-172 Overall, a carbonyl compound (153) is converted to the Michael adduct (155) as outlined in Scheme 55. The actual asymmetric 1,4-addition of the lithiated hydrazone affords the adduct (157) with virtually complete diastereoselection in a variety of cases (Table 3). Some of the products were used for the synthesis of pheromones,169 others were converted to 8-lactones.170 The Michael acceptor (158) also reacts selectively with SAMP hydrazones.171 Tetrahydroquinolindiones of type (159) are prepared from cyclic 1,3-diketones via SAMP derivatives like (160), as indicated in Scheme 56.172... 

Chemical Name Glucuronic acid, y-lactone, l-((4-pyridinylcarbonyl) hydrazone)... 

Treatment of dehydro-L-ascorbic acid (72) with phenyl hydrazine followed by hydroxylamine yielded the hydrazone oxime (73a), cyclization of which in refluxing acetic anhydride gave 4-[l-//u< o-2,3-diacetoxy-(l-hydroxypropyl)]-2-phenyl-l,2,3-triazole-5-carboxylic acid lactone (74a) <77CAR(59)141>. Analogous reactions of the derivatives (72) with substituted aryl hydrazines yielded the triazoles (74b-d). Alternatively, the hydrazone oximes (73a-d) may be treated with HBr in... 

A new class of thiazole-fused diazepinones 79 was prepared by treatment of 2-arylamino-4-coumarinyl-5-formyl thiazoles 78 with hydrazine hydrate in refluxing ethanol to yield the rearranged products via ring-opening by attack of the intermediate hydrazone on the lactone of the coumarin <07SC99>. 

Less frequently, unsaturated 1,4-ketoacids were employed and these 207-209 qj. hydrazones afford 12 directly. Synthesis of 12 is also possible from unsaturated y-lactones 210-21S S-bromo-, " 3-alkylthio-, or 2-hydroxy-l,4-ketoacids. The reaction takes place with simultaneous elimination of water or other residues, although it is claimed that in some cases the elimination of water is slower since the corresponding 4-hydroxy derivatives (13) were isolated.However, the structure of the latter compounds... 

Another type of pyridazine synthesis from pyrones involves coupling of the latter with diazonium salts and rearrangement of the intermediate hydrazones with either aqueous base or acid to pyrid-azinones. Thus, 4-hydroxy 6-methyl-2-pyrone (triacetic lactone) (44)... 

Hydrazon - Keton) 1,2-Dioxolan 5-Oxo-tetramethyl-E13/1, 849 (/J-Lacton + 02) Essigsaure... 

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