ANÁLISIS MICROBIOLÓGICO PARA EL ACEITE DE SEMILLA DE

The samarium carbenoids^^ 75 offer several distinct advantages over the other methylene carbenoids (Scheme 43). Their preparation is extremely mild and high reproducible yields are usually obtained in short reaction times (2-3 h). More importantly, they exhibit unique chemoselectivity as they react exclusively with allylic alcohol substrates.^^ Thus, isolated alkenes or homoallylic alcohols are both inert to samarium carbenoids. In accord with normal carbenoid behaviour, the reaction of acyclic allylic alcohols proceeds with retention o f alkene geometry.

Both (iodomethyl) and (chloromethyl)samarium carbenoid species are easily prepared by the reaction of activated samarium with the corresponding dihalomethane compound (Scheme 43).^^ The metal can either be activated by catalytic amounts of mercury(II) chloride^^ or chlorotrimethylsilane.^^ Molander reported that samarium carbenoids are thermodynamically less stable than zinc carbenoids and decompose exceedingly rapidly via a-elimination to give samarium(II) halide and ethylene. Successful cyclopropanations are therefore carried out at -78°C, followed by warming to room temperature.^^

Sm + XCH2I _{* X ^ ^ S m l}

X=C1 or I 75

Scheme 43

The reactions usually proceed via a hydroxyl-directed mechanism, thus, methylenation occurs from “the same side” as the hydroxy group.^^ For example, an excellent yield of “hydroxyl-directed” cyclopropane could be generated upon treatment of 2-cyclohexen-l-ol 20 with iodomethylsamarium iodide (Scheme 44).^^^ As in the case of the Simmons-Smith carbenoid,^^ no traces o f the trans isomer were observed (Scheme 44). It is notable that in the case of 2-cyclohepten-1 -ol 76, the samarium-based cyclopropanation provides much higher diastereoselectivity (Scheme 44) than that observed under the traditional Simmons-Smith conditions where a 9:1 mixture of diastereomers is o b t a i n e d . I n addition, exposure of the substrate to the samarium(II) iodide reagent for extended periods of time appears to have no effect on

alcohols produced from cyclopropanation of cyclic allylic alcohols by the Simmons- Smith procedure have deereased over prolonged reactions times in the presenee of the zinc carbenoid, no doubt as a eonsequence of the strongly Lewis aeidie eharaeter of zinc halides. OH OH 96% THF/-78°C to r.t. OH OH 64% >30:1 THF/-78°C to r.t. Scheme 44

Molander has proposed a staggered Houk transition strueture for the high diastereoselectivity observed in the electrophilic addition to the a l k e n e . U s i n g this model 77, the favoured transition states for both {E)~ and (Z)-disubstituted allylic alcohols involves R in a position antiperiplanar to the incoming carbenoid so that sterie interactions with are reduced allowing complexation between the hydroxyl group and the carbenoid. Diastereoselectivity therefore increases as the size of R increases and adopts an antiperiplanar position (Scheme 45).

R Sm(Hg)/CH2X2

OH Sm l _OH

X=C1 or I ^-Bu H M e 200:1

Unlike zinc carbenoids,’^ samarium carbenoids gave extremely low yields in more highly hindered allylic alcohols such as tertiary alcohols even those bearing no other substituents around the alkene. For example, 2-phenylbut-3 -en-2-ol 78 was cyclopropanated, utilising both chloroiodomethane and diiodomethane in only 14% and 9% yields, respectively, under the standard reaction conditions (4 equiv. of the carbenoid). A higher yield (53%) was obtained by using an excess of the samarium carbenoid (12 equiv.) (Scheme 46).^^ According to the Houk model, tertiary alcohols force the carbenoid to approach the olefin over an alkyl substituent of the fully substituted carbinol carbon and efficient hydroxyl complexation is consequently inhibited. Decomposition of the carbenoid to ethylene is therefore more dominant than cyclopropanation for highly hindered substrates.

Ph Ph

OH OH 53%

THF, -78°C to r.t.

Me Me

Scheme 46

In addition, a number of allylic alcohols 79-81 also gave poor yields of cyclopropane using samarium carbenoids (Figure 6),^^ which is in contrast to using zinc carbenoids.’^ Once again, steric interactions between R ’ or with R prevent efficient cyclopropanation. 79 80 CH(OH)R^ rUMc, Ph rUmc, Ph or n-Pr H Et CH(OH)M e 81 Figure 6

Imamoto and Takiyama generated Sm(III) carbenoids from the reaction of samarium(II) iodide (formed from samarium and diiodomethane) and geminal dihaloalkanes and these cyclopropanated lithium enolates 82 in good yield (Scheme 47).^^ In addition, Molander reported that the reactivity and selectivity of the carbenoids generated from Sml /ClCH l were similar to those derived from

Sm(Hg)/CH2X2 and it is possible that the same species may be involved in each case (Scheme 47).^^^ However, from a practical standpoint, the procedure involving samarium(II) iodide is less desirable since more samarium and dihalomethane must be used in order to achieve complete conversion of allylic alcohol to product.

OLi OH 62% THF Sml2/ICH2C1 ^ THF/-78°C to r.t. OH Scheme 47

Molander and Harring^^^ had generally found that the (chloromethyl)samarium species gave higher yields than its iodo analogue especially when steric crowding about the allylic alcohol increases. Two explanations were proposed by Molander for this difference in reactivity. The higher yields were attributed to the greater stability of the chloroiodomethane-derived reagent, which would slow down decomposition of the carbenoid to ethylene. The presumably more stable (chloromethyl)samarium reagent would thus be a longer lived species and have more of an opportunity to interact with an allylic alcohol in solution. However, the lower steric demands of a (chloromethyl)samarium species compared to those of an (iodomethyl)samarium species also seems to be a reasonable rationale for the difference in reactivity and cannot be easily dismissed. Although a similar reactivity was noted by Denmark with (chloromethyl)zinc and (iodomethyl)zinc species, the former was found to be less stable. As we have seen, this reactivity difference is clearly illustrated in the cyclopropanation of cyclodecene and the facile reaction with aromatic solvents {vide supra 1.2.1.3, Scheme 13).21