Simmons-Smith reaction enantioselectivity

Chiral Ligand for Asymmetric Catalysis. Dimethyl l-tartrate is a demonstrated chiral ligand for the Ti -catalyzed asymmetric epoxidation of allylic alcohols (Sharpless epoxidation), and the Zn -mediated asymmetric cyclo-propanation of allylic alcohols (Simmons-Smith reaction), see lodomethylzinc Iodide Enantioselectivities in these reactions... 

In 1992 Kobayashi et al. [47] reported the first catalytic and enantioselective cyclo-propanation using the Furukawa modification [48] of the Simmons-Smith reaction of allylic alcohols in the presence of a chiral bis(sulfonamide)-Zn complex, prepared in-situ from the bis(sulfonamide) 63 and diethylzinc. When cinnamyl alcohol 62 was treated with EtgZn (2 equiv.), CHgIg (3 equiv.), and the bis(sulfonamide) 63 (12 mol %) in dichloromethane at -23 °C, the corresponding cyclopropane 64 was obtained in 82 % yield with 76 % ee (Sch. 26). They proposed a transition state XXIII (Fig. 5) in which the chiral zinc complex interacts with the oxygen atom of the allylic alkoxide and the iodine atom of iodomethylzinc moiety. They also reported the use of the bis(sulfonamide)-alkylaluminum complex 65 as the Lewis acidic component catalyzing the Simmons-Smith reaction [49]. 

Besides Cu and Rh, various other metals are known to catalyze the decomposition of diazo compounds [6,7,8,9,10]. Palladium complexes, e.g., are efficient catalysts for the cyclopropanation of electron-deficient C-C double bonds with diazoalkanes [19,20, 21], in contrast to Cu and Rh catalysts which are better suited for reactions with electron-rich olefins. Unfortunately, attempts to develop chiral Pd catalysts for enantioselective cyclopropanation have not been successful so far [22]. More promising results have been obtained with cobalt and ruthenium complexes. These and other chiral metal catalysts, that have been studied besides Cu and Rh complexes, are discussed in chap. 16.3. The same chapter also covers a new direction of research that has recently been taken with the development of catalytic enantioselective Simmons-Smith reactions. 

Small ring synthesis. Simmons-Smith reactions using CH2l2-Et2Zn as reagent are enantioselective in the presence of chiral rrans-I,2-cyclohexanedisulfonamides... 

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. 

The Simmons-Smith reaction is the conversion of olefins to cyclopropanes by the use of halomethylzinc halides or related agents. Charette et al. found that a catalytic amount of chiral titanium-TADDOLate complex 78 was able to induce an enantioselective cyclopropanation of allylic alcohols. After optimisation of the catalytic structure, good yields and enantioselec-tivities were obtained, especially when 3-aryl and 3-heteroaiyl substituted allylic alcohols were used (Scheme 7.47). However, the reaction required the use of a high catalyst loading (25 mol%). 

Several catalytic systems have been reported for the enantioselective Simmons Smith cyclopropanation reaction and, among these, only a few could be used in catalytic amounts. Chiral bis(sulfonamides) derived from cyclo-hexanediamine have been successfully employed as promoters of the enantioselective Simmons-Smith cyclopropanation of a series of allylic alcohols. Excellent results in terms of both yield and stereoselectivity were obtained even with disubstituted allylic alcohols, as shown in Scheme 6.20. Moreover, this methodology could be applied to the cyclopropanation of stannyl and silyl-substituted allylic alcohols, providing an entry to the enantioselective route to stannyl- and silyl-substituted cyclopropanes of potential synthetic intermediates. On the other hand, it must be noted that the presence of a methyl substituent at the 2-position of the allylic alcohol was not well tolerated and led to slow reactions and poor enantioselectivities (ee<50% ee). ... 

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. 

Several procedures deal with optically active auxiliaries employed in stoichiometric amounts or more, but which are not covalently bonded to one of the reagents. These catalysts influence Simmons-Smith type cyclopropanations of allylic alcohols with moderate to excellent enantiose-lectivities. Whereas the reaction of ( )-3-phenyl-2-propen-l-ol (1) with diethylzinc and diiodo-methane in the presence of (17 ,25 )-A,-methylephedrine (2 equivalents) gives an enantiomeric excess of only 24% under optimized conditions107, the same reaction with (/ ,/f)-diethyl tartrate (1.1 equivalents) as ligand affords (1 ) ,27t)-fra i-l-hydroxymethyl-2-phenylcyclopropane (2) with up to 79% ee108, Similar results are achieved with the corresponding (Z)-olefin, and even higher enantioselectivities are obtained for dimethylphenylsilyl-substituted allylic alcohols such as 3109. 

The asymmetric synthesis of cyclopropanes has attracted continual efforts in organic synthesis, due to their relevance in natural products and biologically active compounds. The prevalent methods employed include halomethylmetal mediated processes in the presence of chiral auxiliaries/catalysts (Simmons-Smith-type reactions), transition-metal-catalyzed decomposition of diazoalkanes, Michael-induced ring closures, or asymmetric metalations [8-10,46], However, the asymmetric preparation of unfunctionahzed cyclopropanes remains relatively undisclosed. The enantioselective activation of unactivated C-H bonds via transition-metal catalysis is an area of active research in organic chemistry [47-49]. Recently, a few groups investigated the enantioselective synthesis of cyclopropanes by direct functionalization reactions. 

Kobayashi and coworkers reported catalytic asymmetric Simmons-Smith type reaction of allylic alcohols (Scheme 6.98). In this reaction, Lewis acid (R,R)-(112) prepared by premixing of (1R,2R)-cyclohexane bis-sulfonamide and i-Bu2AlH was found to realize good enantioselectivity. Since, in the similar reaction catalyzed by chiral Zn complex derived from (1R,2R)-cyclohexane bis-sulfonamide and Et2Zn instead of chiral aluminum complex, the same enantioselectivity was observed, chiral Zn carbenoid species formed from (R,R)-(112) and Et2Zn via Al-Zn transmetallation was proposed as an active species [117]. 

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