Simmons-Smith reaction diastereoselective

As (—)-pulegone is not readily available, subsequent work addressed the natural enantiomer by different methods [12], but all completed their synthesis via Snider s enone (17). Asaoka utilised a TMS group as temporary directing volume (Scheme 5) [12a]. Cossy applied a photore-ductive cyclopropane ring opening, which was obtained by a diastereoselective Simmons-Smith reaction [12b]. Schmalz finally used a planar-chiral arene complex to synthesise enone 17 with interesting CrfCO), chemistry [12c]. 

An auxiliary-directed asymmetric Simmons-Smith reaction was used by a Hoff-mann-La Roche group88 for the synthesis of an ethynyl cyclopropane that served as the A-ring precursor to Vitamin D derivatives [Scheme 2.41]. High diastereoselectivity was achieved with the aid of the dioxolane ring prepared from (/ft/f)-(-)-butane-2,3-diol. The acid conditions for hydrolysis of the dioxolane ring were mild enough to leave the cyclopropane ring unperturbed. Dia-stereoselective cyclopropanation of acetals derived from 1,2-di-O-benzyl-L-threi-tol have also been reported 90... 

The chiral version of the Simmons-Smith reaction requires the presence of proper ligands for the organozinc reagent. Representatives are 99, 100, 101 " for cyclopropanation of allylic alcohols. Enals undergo diastereoselective cyclopropanation (de >99%) via acetals with (+)-phenyl exo,ex o-2,3-dihydroxybomane-10-sulfonate. ... 

The zinc metal in the Simmons-Smith reaction was replaced by samarium for the cyclopropanation of allylic alcohols with chloroiodomethane. High yields of cyclopropanes, often with high diastereoselectivities, were obtained using samarium amalgam/diiodomethane. Cyclo-hex-2-enol (115a) gave exclusively s y -bicyclo[4.1.0]heptan-2-ol (116a), no traces of the anti-... 

Although the addition of carbene to a double bond to make a cyclopropane is well known, it is not particularly useful synthetically because of the tendency for extensive side reactions and lack of selectivity for thermally or photochemically generated carbenes. Similar processes involving carbenoids (species that are not free carbenes) are much more useful from the preparative standpoint [91,92]. For example, metal catalyzed decomposition of diazoalkanes usually results in addition to double bonds without the interference of side reactions such as C-H insertions. Consider the possible retrosynthetic approaches to a 1,2-disubstituted cyclopropane shown in Figure 6.8. Disconnection a entails the addition of a methylene across a double bond, a conversion that is often stereospecific e.g., the Simmons-Smith reaction [93]). Disconnections b and c are more problematic, since the issue of cis/trans product isomers (simple diastereoselection) arises. 

Cyclopropanadon The Sm-MCjSiCl combination promotes Simmons-Smith reactions on allylic alcohols, including allenic alcohols. Thus, 2-methylenecyclopropyl carbinols are readily obtained. The diastereoselectivity could be affected by using different promoters. 

Wolfgang Oppolzer s muscone synthesis is the first enantioselective macrocycli-sation. [195] It starts with pentadec-14-ynal, which is converted by hydro-boration and transmetaUation into the corresponding organozinc compound. The ring closure takes place in the presence of catalytic amounts of a diethylzinc/ (-)ejco-3-(diethylamino)bomeol adduct. After work-up, the cyclic allyl alcohol is obtained in 75 % yield and with an ee of 92 %. The hydroxy-group directs the diastereoselective cyclopropanation (Simmons-Smith reaction). The final steps are a Swern oxidation and selective ring-opening of the cyclopropane under Birch conditions. 

A number of chiral acetal derivatives have also proved effective in asymmetric cyclopropanation reactions, with auxiliaries based on tartaric acid proving to be partieularly usefiil. In the case of cyclic a,P unsaturated compounds, di-O-benylthreitol derivatives (see 51) imdergo efficient and diastereoselective Simmons-Smith reactions to give the cyclopropanated products SS. ... 

The reaction was first carried out with the substrate bearing the chiral auxiliary. Scheme 5-64 shows the asymmetric cyclopropanation reaction using 2,4-pentandiol as a chiral auxiliary.115 Scheme 5-65 illustrates the use of optically pure 1,2-frafts-cyclohexanediol as a chiral auxiliary in asymmetric Simmons-Smith cyclopropanation.116 Excellent yield and diastereoselectivity are obtained in most cases. 

Diastereoselective cyclopropanation of enones.1 The homochiral ketals of cyclic a,p-enones obtained by reaction with 1,4-di-O-benzyl-L- or D-threitol2 undergo diastereoselective cyclopropanation on reaction with the Simmons-Smith reagent (8-20 1). The diastereoselectivity is less in the case of ketals of cyclic p, 7-enones (2 1). 

Resolved P-hydroxy sulfoximines derived from cyclic enones undergo dias-tereoselective Simmons-Smith cyclopropanation reactions to give, after thermolysis, cyclopropylketones in high enantiomeric purity (94-98%). Cyclopropanation occurs syn to the hydroxyl group of the P-hydroxy sulfoximine. This method is less diastereoselective for acyclic enones.73... 

The examples mentioned above illustrate the progress in the field of stereocontrolled cyclopropanation. Nowadays, the asymmetric Simmons Smith cyclopropanation may well be mentioned in the line with other asymmetric reactions like epoxidation or dihydroxylation. Fligh enan-tioselectivity and diastereoselectivity can be... 

An early stage in the synthesis of the antifungal metabolite FR-900848 exploited a double Simmons-Smith cyclopropanation directed by two di-isopropyl tartrate acetals [Scheme 2.42] 9192 The diastereoselectivity of the reaction can be attributed to intramolecular delivery of a zinc carbenoid co-ordinated to one of the ester carbonyls and an oxygen of the dioxolane ring.93 Note the use of the Noyori protocol (see above) for the bis-dioxolanation of the highly reactive mu-conaldehyde ... 

The diastereoselective and enantioselective preparation of cyclopropanes has attracted attention since chiral cyclopropanes were found to occur in many natural products [11]. Moreover, cyclopropanes are useful intermediates in organic synthesis. There are many methods of cyclopropane ring opening that transfer stereochemical information from the substrate to acyclic products in a stereocontrolled manner [12]. Among the methods used for the preparation of cyclopropanes from olehns, the Simmons-Smith and related reactions as well as reactions of diazoalkanes catalyzed by rhodium, copper and cobalt salts have frequently been applied [13]. The preparatively simple Makosza reaction [14] has scarcely been used. 

This method was utilized for the synthesis of the four stereoisomers of coronamic acid [17]. The ( )-allylic (3-D-glucopyranoside 3 was cyclopropanated under Simmons-Smith conditions at — 30°C with high diastereoselectivity (>100 1). The reaction of the corresponding (Z)-allylic... 

As in the case of the / -series, the a-anomer with a free hydroxy group at C2 also showed good diastereoselectivity (13 1) in the Simmons-Smith cyclopropanation with diethylzinc/ diiodomethane in fert-butyl methyl ether at 0 C. Several substituted allylic ethers, e g. 70, were subjected to this reaction with success. While the auxiliary can be easily removed by a ring-contraction method to give cyclopropylmethanol derivatives, this methodology provides an efficient method to prepare both enantiomers. 

Similarly, reactions of the modified Simmons-Smith reagent with acyclic (Z)-allylic alcohols are highly diastereoselective (Table 3) while those of the corresponding -isomers are rather unselcctive40. 

Cycloaddition reactions of ketenes to imines derived from glycosylamine and aldehydes provide access to P-lactams, although the level of selectivity observed with these N-linked auxiliaries is modest. The alkenyl moiety of glycoside 212 undergoes diastereoselective epoxidation using peracid in 80 %d.e. Simmons-Smith cyclopropanation of 212 was reported earlier (Vol. 25, p.335). 

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