Stereoselectivity Simmons-Smith cyclopropanation

Recently, Charette et al. have also demonstrated this behavior in the stereoselective cyciopropanations of a number of enantiopure acyclic allylic ethers [47]. The high degree of acyclic stereocontrol in the Simmons-Smith cyclopropanation has been extended to synthesis several times, most notably in the synthesis of small biomolecules. Schollkopf et al. utilized this method in their syntheses of cyclopropane-containing amino acids [48 a, b]. The synthesis of a cyclopropane-containing nucleoside was also preformed using acyclic stereocontrol [48c]. 

The stereoselectivity of conjugate addition and cyclopropanation of the chiral nitrovinyldioxolanes 17 can be effectively controlled <96TL6307>, and good selectivity is observed in the ultrasound-promoted cycloaddition of nitrile oxides to alkenyldioxolanes 18 <95MI877,95JOC7701 >. Asymmetric Simmons-Smith cyclopropanation of 19 proceeds with... 

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). ... 

Some of the evidence for this comes from a reaction that not only throws light on to the mechanism of Simmons-Smith cyclopropanations, but makes them of even greater value in synthesis. When an allylic alcohol is cyclopropanated, the new methylene group adds stereoselectively to the same face of the double bond as the alcohol group. 

Stereoselective samarium-based Simmons-Smith cyclopropanation of cyclopentyl allylic alcohols is the key step in the synthesis of the precursor of 1,25-dihydroxy vitamin The... 

Stereoselective samarium-based Simmons-Smith cyclopropanation of cyclopentyl allylic alcohols is the key step in the synthesis of the precursor of 1,25-dihydroxy vitamin D3.128 The desired chirality was generated in one case under the influence of the two stereogenic centers on the (R,/ )-butane-2,3-diol acetal 121 and in the other case was directed entirely by the allylic hydroxy group of 122. 

A process for the asymmetric cyclopropanation of the enol ethers of cyclic and acyclic ketones has been developed by Tai [109-111]. In this process, a 2-symmetric acetal is isomerized to a hydroxy enol ether which serves as substrate or the Simmons-Smith cyclopropanation, as shown in Scheme 6.29. The stereoselectivity is nearly perfect, but a mechanistic hypothesis has not been proposed. The auxiliary may be removed either by hydrolysis, to give the methyl ketone, or by oxidation of the alcohol and p-elimination [111]. 

Consider the C2-symmetrical precursor 28, in which both acetoxy groups are homotopic (identical). Desymmetrization by hydrolysis of just one acetyl residue could be readily achieved late in a projected synthesis. This would enable a hydroxyl-directed Simmons-Smith cyclopropanation. Mitsunobu esterihcation (with inversion of configuration) would then set the stage for a concluding alkyne metathesis [39] (Scheme 3.24). This approach does not yet address the formation of the stereogenic center in the middle of the target structure, be it by oxidation to a ketone and stereoselective reduction. 

When trans-cyclododecen-3-ol is subjected to CH2l2-Cu/Zn treatment the trans,anti-bicyclotridecane (66) is produced in a highly stereoselective manner. The Simmons-Smith cyclopropanation procedure has also been employed in a new synthesis of (+ )-caryophyllene and in the preparation of the parent cyclohepta[a]acenaphthyl-enyl cation. ... 

Cyclopropanation with organometallic carbenoid reagents is one of the most popular. Advantages include broad substrates generality, tolerance of a variety of functional groups, and high stereoselectivity. Among the many efforts, the Simmons-Smith cyclopropanation is the most notable. 

Cyclopropanation of iron complex 301 also progressed but the stereoselectivity was moderate (Scheme 1.147) [213]. Iron complex 301 was also useful for the Simmons-Smith cyclopropanation reaction. 

Chemo- and stereoselective reduction of (56) to (55) is achieved In highest yield by sodium borohydride in ethanol. The isolated ketone is reduced more rapidly than the enone and (55) is the equatorial alcohol. Protection moves the double bond out of conjugation and even the distant OH group in (54) successfully controls the stereochemistry of the Simmons-Smith reaction. No cyclopropanation occurred unless the OH group was there. Synthesis ... 

A simpler example of this kind of stereochemical control is the cyclopropanation of cyclopenten-2-ol (5) by the Simmons-Smith reagent in which the cij-biciclo[3.1.0]hexan-2-ol (7) is the diastereomer exclusively formed. As in the case of the hydrogen in strychnine, the methylene enters stereoselectively by intramolecular transference from an intermediate complex ( . 

All these methods using carbenes, metal complexes of carbenes or carbenoids are stereospecific in that the geometry of the alkene is faithfully reproduced in the stereochemistry of the cyclopropane so trans-61 gives trans-68 specifically. They can also be stereoselective, particularly the Simmons-Smith on allylic alcohols thus the cyclopropane in 68 is on the same side of the alkene as the OH group in 67. We now come to a widely used method that is not stereospecific on the alkene. 

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