Cyclopropanated lactones

The seminal enantioselective allylic alcohols epoxidation realized by Katsuki and Sharpless [18] to which other similarly steroselective reactions soon followed (e.g., bishydroxyla-tion, cyclopropanation, lactonization and catalytic hydrogenation) have been invaluable for this purpose. One of the most significant applications, as far as drug synthesis is concerned, of the Sharpless method from the innumerable ones which have been found in the past 20 years is the routine preparation (Fig. 6) of antipodal pairs of known chirality of (3-blockers such as propranolol (5) [19]. 

As shown in Scheme 37, Corey developed an effective synthetic route toward polycyclic lactones such as 83 with rigid and compact structures on the basis of tiie Cu-catalyzed intramolecular (2+1) cycloaddition of allyl diazomalonate 82 followed by the treatment of cyclopropane lactone thus obtained with MesSiOTf and a small amount of water [53]. 

Another interesting example of the rearrangement has recently been reported by Samet and coworkers [26], who describe a reaction of levoglucosenone with sulfur ylides to form unusual cyclopropane derivatives. These annulated cyclopropanes were smoothly converted by 30% aqueous hydrogen peroxide in acetic acid to cyclo-propanecarboxylic acids. The final acid hydrolysis (MeOH/HCl) converted them into synthetically valuable cyclopropanated lactones. This case of the Baeyer-Villiger rearrangement reaction is depicted in Scheme 9.9. 

SCHEME 9.9 Samet s synthesis of cyclopropanated lactones via the Baeyer-Villiger rearrangement. 

Varadarajan, S., Mohapatra, D.K., and Datta, A. (1998) Studies towards the total syntheses of solandelactones stereoselective synthesis of the cyclopropane-lactone segment Tetrahedron Lett., 39,1075-1078. 

Chiral Alcohols and Lactones. HLAT) has been widely used for stereoselective oxidations of a variety of prochiral diols to lactones on a preparative scale. In most cases pro-(3) hydroxyl is oxidized irrespective of the substituents. The method is apphcable among others to tit-1,2-bis(hydroxymethyl) derivatives of cyclopropane, cyclobutane, cyclohexane, and cyclohexene. Resulting y-lactones are isolated in 68—90% yields and of 100% (164,165). 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Diazomalonic esters serve as intermediates for the synthesis of a wide variety of compounds including cyclopropanes, cyclo-propenes, cycloheptatrienes, sulfur ylides, lactones, and substituted malonates. ... 

In recent years, the variety of useful diazo substrates for asymmetric intramolecular cyclopropanation processes has really expanded. As another example, Charette and Wurz have reported the first example of an intramolecular cyclopropanation involving a-nitro-a-diazo carbonyl compounds.This reaction, catalysed by Rh2[(S)-DOSP]4, led to the formation of nine-membered nitrocyclopropyl lactones in good yields and enantioselectivities with extremely high diastereoselectivities (Scheme 6.17). This novel methodology constituted an efficient entry into chiral functionalised macrocyclic-fused cyclopropane oc-amino acids. 

The chemistry of a-haloketones, a-haloaldehydes and a-haloimines Nitrones, nitronates and nitroxides Crown ethers and analogs Cyclopropane derived reactive intermediates Synthesis of carboxylic acids, esters and their derivatives The silicon-heteroatom bond Syntheses of lactones and lactams The syntheses of sulphones, sulphoxides and cyclic sulphides... 

The next step is not immediately obvious. The generation of an ethyl ester from a lactone can be accommodated by transesterification (we might alternatively consider esterification of the free hydroxyacid). The incorporation of chlorine where we effectively had the alcohol part of the lactone leads us to nucleophilic substitution. That it can be SnI is a consequence of the tertiary site. Cyclopropane ring formation from an Sn2 reaction in which an enolate anion displaces a halide should be deducible from the structural relationships and basic conditions. 

Vicinally donor-acceptor-substituted cyclopropanol carboxylic esters have been proven to be versatile synthetic building blocks in organic synthesis [11]. They readily undergo a retroaldol reaction, thus creating a stable enolate that at the same time can be considered as a homoenolate in relation to the newly formed carbonyl function. Shimada et al. applied this strategy to the preparation of y-substituted lactones starting from cyclopropane 21 (Scheme 3) [12]. 

Intramolecular cyclopropanations are also well documented in the literature. It has been shown by Koskinen and co-workers that the cyclopropanation of diazomalonate 57, illustrated in Figure 9.18, using benzyl bis(oxazoline) 40 and copper(I) triflate afforded lactone 58 in 73% yield and 32% ee. Nishiyama and coworkers showed that cyclopropanations of diazoacetates 59a-c proceeded in yields ranging from 79-93% and 24-86% ee (Table 9.6, Fig. 9.18, p. 544). ... 

Treatment of the bicyclic dibromo-y-lactone 1 with DBU in acetonitrile at 0-20 °C gave the tricyclic lactone 2 with formation of the cyclopropane ring in 90% yield66. 

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