Decarboxylation ring contraction

Cyclopropyl ketones. Cyclopropyl ketones (2) are obtained in 50-100% yield when a-acyl-7-butyrolactones (1) are heated in DMSO or DMF with catalytic amounts of alkali metal halides (particularly NaCl or NaBr), quaternary ammonium halides [(CH3)4NBr], or DABCO. Water is not necessary for this decarboxylative ring contraction. ... 

Synthesis of uroporphyrinogen III from 6-ALA via porphobilinogen. - 2) C-Methylation of uroporphyrinogen III by a series of different methyltransferases with use of S-adenosylmethionine (SAM), decarboxylation, ring contraction, and incorporation of cobalt with formation of cobyrinic acid, the simplest representative of the naturally occurring corrins. - 3) Conversion of cobyrinic acid to cobalamin and then to the coenzyme form of V. B 2. 

Sodium bromide Decarboxylative ring contraction Cyclopropyl ketones from -acyl-y-lactones... 

The ring-contracted analog of alphaprodine is prepared by a variation of the scheme above. Alkylation of 109 with ethyl bromoacetate affords the lower homolog diester (115). Dieckmann cyclization followed by saponification-decarboxylation yields the pyrrolidine (116). Reaction with phenylmagnesium bromide leads to the condensation product (117) acylation with propionic anhydride gives the analgesic agent prolidine (118)... 

Ring contraction of coumarins is used for the preparation of benzo[Z>]furans. Alkaline degradation of the 3-halo-, 4-halo- or 3,4-dihalo-coumarins gives the coumarilic acids (Scheme 104). The coumarilic acids are decarboxylated to the corresponding benzo[Z> ]f urans. Basic mercury(II) oxide oxidation of 4-phenylcoumarin (neoflavanoid) yields the 3-phenyl-benzo[/>]furan (71IJC1316). 

The formation of this dicarboxylic acid derivative is of some interest. The free ligand quinone is known to undergo a benzilic acid rearrangement with concomitant ring contraction, followed by decarboxylation to yield a diazafluoreneone on treatment with base (Fig. 8-42). 

For example, irradiation (in a quartz immersion apparatus with a high-pressure Hg lamp) of compounds 18a and 18c in acetonitrile (or of 18b in methanol) produces 3-formylindoles 20a-c (37-70%) through the formation of benzoxazepines 19a-c, followed by ring-contraction (and final decarboxylation in the case of 19b) [19, 20]. In a typical experiment, the preparative-scale irradiation of 18c, in acetone (400 W, high-pressure Hg lamp, Pyrex filter, 18 min) allowed the isolation of benzoxazepine 19c in 94% yield. The latter compound, when irradiated for 8h in acetonitrile by using the same light source without the Pyrex filter, gave indole 20c in 70% yield (Scheme 12.6) [19]. 

E is facile. Dehydrochlorination provides the aromatic products 233. An alternatively possible HC1 elimination/electrocyclization/decarboxylation pathway was excluded, since lactone 230B was thermally stable under the reaction conditions in the absence of the catalyst. (NHC)Cu(I) catalyst 232 gave comparable or better yields than 231 in these ATRC/ring contraction sequences, while other (NHC)Cu(I) complexes provided considerably lower yields [320]. Chlorinated cyclic compounds arising from ATRC can also be transformed to chlorinated furans [321]. 

One synthesis of cyclopentenone [80], requiring a resolution, involved initial ring contraction of phenol when treated with alkaline hypochlorite (49). Resolution of the resulting cis acid [85] was effected with brucine. The desired enantiomer [86] formed the more soluble brucine salt and was thus obtained from the mother liquors of the initial resolution. Oxidative decarboxylation with lead tetracetate, partial dechlorination with chro-mous chloride, and alcohol protection gave chloro enone [87]. Zinc-silver couple (50) dechlorinated [87] to the desired cyclopentenone [80]. 

The structure 61 for precorrin-6A forced a complete change in the way the biosynthesis of vitamin B12 was viewed. This structure was full of surprises (a) the ring contraction step does not occur near the end of the pathway but has been completed at precorrin-6A 61 and is possibly carried out even earlier (b) oxidation has occurred prior to the formation of precorrin-6A and reduction is needed after it so the oxidation level along the pathway is not constant (c) decarboxylation of the C-12 acetate group is not an early step it occurs on the pathway beyond precorrin-6A (d) the 12a-methyl group of hydrogenobyrinic acid 60 is introduced initially at C-11 with subsequent migration to C-12. 

Two more complicated ring-contraction reactions, both yielding 4-amino-3-oxothiadiazoline 1,1-dioxides, are known. Disselnkoetter reported (71GEP1961864) that the reaction of 1,4,3,5-oxathiadiazine 127 with hydrogen cyanide produced imino derivatives 128, which were easily hydrolyzed to the corresponding oxo derivatives 89b by acid treatment (Scheme 49). The course of the reaction may involve addition of cyanide ion, decarboxylation of the resulting carbamic acid, and a nucleophilic attack at the carbonitrile group, as shown in Scheme 49. 

A biosynthetic scheme (Scheme 4.6) involving an oxidative decarboxylation and ring contraction (4.50 4.51) has been devised to accommodate these results. 

R3 = OH) could not be decarboxylated.46 Similar resistance to decarboxylation has been observed with a compound obtained by acid hydrolysis of 9 (R1 = C02Me R2 = R3 = H) and assumed to be 9 (R1 = C02H R2 = R3 = H). It has been shown that ring contraction (see Section III,A) takes place during the hydrolysis and the compound formed has the enolic structure of 55 (Rl = R2 = R4 = R5 = H R3 = OH), which would explain the fact that it cannot easily be decarboxylated.47 Loev et al.iK have recently reported that the Stobbe condensation of 2-amino-5-chlorobenzophenone with diethyl succinate directly gave 55 (R1 = R2 = R5 = H R3 = Ph R4 = Cl) and none of the desired 56 (R1 = H R2 = C02H R3 = Ph R4 = Cl). 

Dihydroxykaurenolide (65) has been isolated from Gihherella fujikuroi. It was converted via the C-2 olefin into dihydro-7-hydroxykaurenolide, and the ready decarboxylation of the diketone formed on oxidation located the additional oxygen function at C-3. The ring-contraction of the corresponding 7a-toluene-p-sulphonate has been examined as a route to gibberellin A14 aldehyde (66). 17-Hydroxy-( — )-kaur-15-en-19-oic acid has been isolated from Enhydra fhictuans. 

Benzofurans can be prepared from a-halo-coumarin compoimds. Base-catalyzed ring-contraction followed by dehydrative decarboxylation gives rise to the desired benzofuran. 

---