Simmons-Smith reaction, cyclopropane derivatives from

The mechanism for the formation of this carbenoid and for its reaction with alkenes need not concern us here. Just remember that it reacts as though it is methylene. The Simmons-Smith reaction is an excellent way to prepare cyclopropane derivatives from alkenes, as shown in the following examples. Note the stereochemistry in the second equation. 

The reaction is known as the Simmons-Smith reaction, after the two chemists at the DuPont chemical factory who discovered it in 1958. Even after several decades, it is the most important way of making cyclopropane compounds, though nowadays a variant that uses more easily handled starting materials is often used. Diethyl zinc replaces the Zn/Cu couple of the traditional Simmons-Smitji reaction. In this example, a double cyclopropanation on a C2 symmetric diene derived from tartaric acid gives very good stereoselectivity for reasons we will soon discuss. 

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 Simmons-Smith reaction is an efficient and powerful method for synthesizing cyclopropanes from alkenes [43]. Allylic alcohols are reactive and widely used as substrates, whereas a,j8-unsaturated carbonyl compounds are unreactive. In 1988, Ambler and Davies [44] reported the electrophilic addition of methylene to a,/3-unsaturated acyl ligands attached to the chiral-at-metal iron complex. The reaction of the racemic iron complex 60 with diethylzinc and diiodomethane in the presence of ZnCl2 afforded the c/s-cyclopropane derivatives 61a and 61b in 93 % yield in 24 1 ratio (Sch. 24). 

The fact that the Simmons-Smith reaction is regio- and stereoselective enabled the preparation of tritium containing cyclopropane derivatives useful for biological studies. The tritiated diiodomethane was prepared by reduction of iodoform with sodium arsenite in the presence of tritiated water. The carbene generated from tritiodiiodomethane and triisobutylaluminum in chloroform underwent regioselective addition to the unhindered double bond in perillyl alcohol (34). ... 

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). ... 

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... 

More recently, dioxaborolane derived from (RR)- +)-N,N,N, W -tetramethyltartaric acid diamide has been used as an efficient chiral controller in Simmons Smith cyclopropanation reaction of allylic alcohols to produce substituted cyclopropyl methanols in high... 

No matter how they are generated, carbenes and carbenoids undergo four typical reactions. The most widely used reaction is cyclopropanation, or addition to a TT bond. The mechanism is a concerted [2 + 1] cycloaddition (see Chapter 4). The carbenes derived from chloroform and bromoform can be used to add CX2 to a 7T bond to give a dihalocyclopropane, while the Simmons-Smith reagent adds CH2. Carbenoids generated from diazoalkanes with catalytic Rh(II) or Cu(II) also undergo cyclopropanations. 

Dimethylsulfonium methylide and dimethylsulfoxonium methylide also differ in their reachons with a,p-unsaturated carbonyl compounds. The sulfonium ylide reacts at the carbonyl group to form an epoxide, but with the sulfoxonium ylide a cyclopropane derivative is obtained by Michael addihon to the carbon-carbon double bond. The difference is again due to the fact that the kinehcally favoured reachon of the sulfonium yhde with the carbonyl group is irreversible, whereas the corresponding reaction with the sulfoxonium yhde is reversible, allowing preferenhal formahon of the thermodynamically more stable product from the Michael addihon. For example, the cyclopropane 112 is obtained from the reaction of dimethylsulfoxonium methylide with the enone 111 (1.105). Other methods for the formahon of cyclopropanes include carbene and Simmons-Smith-type... 

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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