Hydrogenation, catalytic cyclopropanes

Cyclopropane ring scission occurs readily either under reducing conditions or upon the action of electrophilic or nucleophilic agents. These possibilities offer multiple options for the synthetic utilization of the cyclopropane moiety in organic synthesis. One of the most important applications is based upon the use of the cyclopropanation-catalytic hydrogenation sequence as a method for the creation of the gem-dimethyl moiety, a fragment frequently encountered in many naturally occurring compounds. A typical example is shown in Scheme 2.161. 

Much of the recent work on the cyclopropane-propylene isomerization has had one of two objectives, either to try and determine which of the two reaction paths suggested by the early workers is involved, or to test the various theories of unimolecular reactions. Comer and Pease (1945), using catalytic hydrogenation to analyse their reaction product, but otherwise working under similar conditions to Chambers and Kistiakow-sky, suggested that all the results obtained could be represented just as well by the reaction scheme... 

It was mentioned earlier that catalytic hydrogenation of protoporphyrin-IX (19) produces mesoporphyrin-IX (46), and that this type of vinyl modification has been used in structural degradation methods. The vinyl group can also be modified for degradative purposes by addition of diazoacetic ester, which produces the corresponding cyclopropane derivatives... 

The development of asymmetric cyclopropanation protocols has been actively studied and in recent years remarkable progress has been made. The extent of chiral induction that can now be obtained in these reactions approaches the level of other classic catalytic asymmetric reactions on alkenes, such as catalytic hydrogenation and the Sharpless epoxidation.37... 

In the second, aprotic decomposition of tosylhydrazone 101 was shown to proceed with conventional cyclopropane ring formation.148 On catalytic hydrogenation, one of the two products (102) was converted to tricyclo[3.3.0.03, 7]-octane (103) (Scheme 20). This hydrocarbon is not only a dehydrobicyclo[3.3.01-octane but is also of interest because of its bisnor relationship to adamantane. 

The ring expansion of the benzoxepinones 134 to benzoxocinones 136 involved a cyclopropanation with diazomethane in the presence of palladium acetate and a catalytic hydrogenation. The cleavage of the more labile internal bond in the cyclopropyl derivatives 135 leads to the eight-membered ketones 136 exclusively in excellent yields (90-95%). Reduction of ketones 136 with sodium borohydride affords the hydroxy derivatives 137 in a stereo-controlled manner (Scheme 34) <2002CC634>. 

The cleavage of a single bond (allylic or benzylic C-0 and C-N, C-X, C-S, N-N, N-O, 0-0 bonds, opening of cyclopropane, epoxides and aziridine by catalytic hydrogenation) is known as hydrogenolysis. Dehalogenation is favoured by basic conditions in the presence of a metal catalyst, Pd. The ease of dehalogenation decreases in the order I > Br > Cl > R... 

Catalytic hydrogenation of alkyl-substituted cyclopropanes usually breaks the least hindered bond . This constitutes a nice method for converting ketones into geminal dimethyl compounds (equation 13) , a principle realized for the syntheses of natural and unnaturaP products. 

Catalytic hydrogenation will usually open the less hindered bond adjacent to the carbonyl-substituted cyclopropane carbon Therefore, construction of the sinularene skeleton has become possible (cleavage of bond a) on the other hand, Cr(II) breaks the more shielded C-C bond (cleavage of bond b) in a very similar compound yielding the longifolene system (equation 34) . 

Catalytic hydrogenation of electrophilic cyclopropanes normally yields ring-opened products (equation 229) . Catalytic hydrogenation of 1,1-cyclopropanedicarbo-nitriles (659) gives rise to )5-cyanoenamines (661) via hydrogenation of the dinitriles (660) (equation 230) Hydrogenation of the tetramethyl compound 662 provides 663 via... 

The cyclopropane chemical reactivity, which closely resembles that of an olefinic double bond, stems from the electronic properties of this three-membered carbocycle Effectively, cyclopropyl and olefinic groups interact with neighbouring 7c-electron systems and p-electron centres they both add acids, halogens and ozone, undergo catalytic hydrogenation and cycloaddition, form metal complexes, etc. 

Hydrogenolysis of the cyclopropane ring of the cyclopropa[e]pyrrolo-[ 1,2-a]pyrimidine 6, on catalytic hydrogenation in the presence of 5% palladium on carbon under atmospheric pressure, proceeded in two ways, giving rise to a mixture of the pyrrolodiazepine 20 (R = Ac, R = H) and the pyrrolopyrimidine 21 (R = H). ... 

The lactone-directed intramolecular Diels-Alder cycloaddition was the key step in D.F. Taber s synthesis of trans-dihydroconfertifolin. During the endgame, the Simmons-Smith cyclopropanation was utiiized to install the gem-dimethyl group at C4. The trisubstituted alkene was cyclopropanated in excellent yield and the resulting cyclopropane was subjected to catalytic hydrogenation. 

Olefins are very important industrial raw materials, and much effort has been devoted toward using them as substrates in asymmetric synthesis [811, 812, 853], The industrial synthesis of nonracemic a-aminoacids by catalytic hydrogenation was ore of the first important uses of olefins in asymmetric synthesis [859], Today, the Sharpless epoxidation of allylic alcohols [807, 808, 809] is one of the most popular methods in asymmetric synthesis. The importance of pyrethrinoid pesticides, bearing a cyclopropane skeleton, justifies the efforts devoted to the asymmetric synthesis of cyclopropanes from alkenes [811,812, 937],... 

Reduction of cyclopropyl methyl ketone has been attempted by four different methods 415 Only poor yields of the alcohol were obtained by use of sodium and alcohol on use of LiAlH4 difficulties were encountered for larger batches and catalytic hydrogenation with Raney nickel caused partial cleavage of the cyclopropane ring however, excellent yields of 1-cyclopropylethanol were obtained in the presence of a copper-chromium oxide catalyst activated by barium, at 100°. 

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]. 

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