Jean-Pierre Deprés

Improved preparation of angelate esters

Abstract A new procedure has been developed for the efficient preparation of angelate esters from alcohols. The alcohol is treated in dry toluene at 70–80 °C for 19–36 h with a mixed anhydride prepared from angelic acid and 2,4,6-trichlorobenzoyl chloride. In the absence of base, no tiglate ester is produced.

Enantiocontrolled total synthesis of (+)-bakkenolide-A

Abstract An efficient, stereoselective total synthesis of natural bakkenolide-A has been effected from (S)-1,6-dimethyl-1-cyclohexene, which can be obtained from 2-methyl-2-cyclohexen-1-one in 3 high-yield steps.

A new two-carbon olefin homologation procedure that leads to α-chloroenones. An efficient synthesis of d,1-muscone

Abstract Dichloroketene-olefin cycloadducts, α, α-dichlorocyclobutanones, are easily converted to α -chloroenones through a 3-step (2-pot) sequence of reactions. The over all result is the insertion of a functionalized 2-carbon unit between the original olefinic carbons. The efficiency of the method is demonstrated by a high-yield synthesis of d , 1 -muscone.

Synthesis of ring modified prostaglandins

Abstract The total syntheses of the ring modified prostaglandins 8–12 , 16 , 18 , 20 , and 22 are described.

Direct approach to the bakkanes: A synthesis of (±)-homogynolide-B

Abstract A short synthesis of racemic homogynolide-B is described. The key step of the approach, cycloaddition of dichloroketene with the 2,2-dimethyltrimethylene acetal of 2,3-dimethyl-3-cyclohexen-1-one, proceeds with excellent selectivity and in high yield.

Stereoselective synthesis of (-)-homogynolide-A

Abstract (−)-Homogynolide-A, a spiro β-methylene-γ-butyrolactone sesquiterpene from Homogyne alpina , has been stereoselectivity prepared in natural form from S -(+)-carvone.

Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale

11-Nor PGE2 was prepared in our laboratory several years ago and used to obtain the corresponding ring-expanded γ-butyrolactam, γ-butyrolactone, and cyclopentanone derivatives. The conversion of a cyclobutanone into a cyclopentanone had relatively little precedent and merited further study. It was soon found that the presence of a single chlorine adjacent to the carbonyl not only greatly accelerated the reaction with ethereal diazomethane, but also substantially enhanced its regioselectivity; not surprisingly, a second chlorine further increased both. The confluence of this finding and the discovery by Krepski and Hassner that the presence of phosphorus oxychloride significantly improved the Zn-mediated dehalogenation procedure for the preparation of α,α-dichlorocyclobutanones from olefins provided the starting point for decades worth of exciting adventures in natural product synthesis. A wide variety of naturally occurring 5-membered carbocycles (e.g., hirsutanes, cuparenones, bakkanes, guaianolides, azulenes) could thus be prepared by using dichloroketene-olefin cycloaddition, followed by regioselective one-carbon ring expansion with diazomethane. Importantly, it was also found that natural γ-butyrolactones (e.g., β-oxygenated γ-butyrolactones, lactone fatty acids) could be secured through regioselective Baeyer-Villiger oxidation of cycloadducts with m-CPBA and that naturally occurring γ-butyrolactam derivatives (e.g., amino acids, pyrrolidines, pyrrolizidines, indolizidines) could be efficiently obtained by regioselective Beckmann ring expansion of the adducts with O-(mesitylenesulfonyl)hydroxylamine (Tamuras reagent). These 5-membered carbocycles, γ-butyrolactones, and γ-butyrolactam derivatives were generally secured in enantiopure form through the use of either intrinsically chiral olefins or olefins bearing Stericol, a highly effective chiral auxiliary developed specifically for this three-atom olefin annelation approach. In addition, considerable useful chemistry has been developed in the context of this synthesis program. This includes new methods for olefin vicinal dicarboxylation, β-methylene-γ-butyrolactonization, γ-butyrolactone and δ-valerolactone α-methylenations, transesterification, angelic ester synthesis, chiral enol and ynol ether preparations, dichloroacetylene synthesis, and trans, trans hydroxy triad introduction. This versatile dichlorocyclobutanone-centered approach to natural product synthesis, together with the attendant new methods that have been developed, forms the basis of this Account, which is presented as an evolutionary tale. It is hoped that the Account will stimulate other research groups to seek to exploit the rich chemistry of dichlorocyclobutanones for possible solutions to problems in organic synthesis.

Stereoselective synthesis of homogynolide-A, A bakkane from homogyne alpina

Abstract Homogynolide-A, an antifeedant sesquiterpene, has been stereoselectively prepared from benzoquinone.

Addition of organolithium compounds to tricarbonyl(tropone)iron complexes: experimental and structural studies

Abstract The regioselectivity (1,2 vs. 1,4) in the nucleophilic addition of organolithium reagents to tropone(tricarbonyl)iron complexes has been studied and found to be correlated with the relative hardness of the nucleophile (HSAB principle). X-ray structures of several 1,2 and 1,4 adducts are reported.

Stereoselective bakkane synthesis: (±)palmosalide C

Palmosalide C, a spiro β,γ-epoxy-γ-butyrolactone sesquiterpene from the soft coral Coelogorgia palmosa, has been stereoselectivity prepared in racemic form from 1,6-dimethylcyclohexene.