Simmons-Smith cyclopropanations, allylic alcohols

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. 

The landmark report by Winstein et al. (Scheme 3.6) on the powerful accelerating and directing effect of a proximal hydroxyl group would become one of the most critical in the development of the Simmons-Smith cyclopropanation reactions [11]. A clear syw directing effect is observed, implying coordination of the reagent to the alcohol before methylene transfer. This characteristic served as the basis of subsequent developments for stereocontrolled reactions with many classes of chiral allylic cycloalkenols and indirectly for chiral auxiliaries and catalysts. A full understanding of this phenomenon would not only be informative, but it would have practical applications in the rationalization of asymmetric catalytic reactions. 

Scheme 6.20 Simmons-Smith cyclopropanations of allylic alcohols with cyclohexanediamine-derived bis(snlfonamides) ligands.

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). ... 

Corey exploited the remarkable configurational stability of cyclopropyllithiums in his synthesis of hybridalactone. The stannane 28 was made by Simmons-Smith cyclopropanation of the allylic alcohol 27 and resolved by formation of an O-methyl mandelate ester. Transmetallation of 29 with 2 equiv. BuLi gave an organolithium which retained its stereochemistry even in THF over a period of 3 h at 0 °C, finally adding to 31 to give 32. 

The alkylboronic ester of chiral diol was used as the most efficient chiral ligand for the enantioselective Simmons-Smith cyclopropanation of substituted allylic alcohols (Equation (252)).1056-1059... 

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. 

Asymmetric Simmons-Smith cyclopropanation using no covalent-bound auxiliary but a chiral catalyst have only been successful with allylic alcohols so far. Fujisawa had shown that allylic alcohols such as 38 are converted into the corresponding alcoholate by Et2Zn (1.1 equivalents) first [31]. Addition of diethyltartrate (1.1 equivalents) results in the formation of an intermediate 39, which is cyclopropanated under Furukawa conditions (Et2Zn + CH2I2) to give compound... 

The excellent affinity of the alkylzinc reagent for ethereal oxygen in the Simmons-Smith cyclopropanation of allylic alcohols and ethers has been exploited for the asymmetric cyclopropanation of a, -unsaturated aldehydes and ketones using homochiral protecting groups. ... 

The Simmons-Smith cyclopropanation of the same 3-(2-phenylcydopropyl)prop-2-enol (110) in its racemic form afforded an inseparable mixture of and a t/-bicyclopropanes 111 in a 1.3 1 ratio. Therefore, the Charette protocol (p 286) was used first to prepare the required allylic alcohol in its optically pure form and the cyclopropanation was carried out in the presence of the tartrate derived dioxaborolane 93. By using (+)- and (— )-tartrate derived dioxaborolane 93, both the syn- and antf-bicyclopropyls 111 were obtained. The diastereoselectivities observed in their formation were consistently greater than 12 1. ... 

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... 

The Simmons-Smith cyclopropanation reaction Stereochemically controlled epoxidations Regio- and Stereocontrolled Reactions with Nucleophiles Claisen-Cope rearrangements Stereochemistry in the Claisen-Cope rearrangement The Claisen-Ireland rearrangement Pd-catalysed reactions of allylic alcohols Pd-allyl acetate complexes Stereochemistry of Pd-allyl cation complexes Pd and monoepoxides of dienes The control of remote chirality Recent developments Summary... 

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 combination of resolution and diastereofacial cyclopropanation has been used to prepare a variety of cyclopropyl ketones with high optical purity77. Optically active lithiated (S)-N,S-dimethyl-S-phenylsulfoximine (17) is added to prostereogenic enones such as 16, and the resulting diastereomeric allylic alcohols 18 are separated by column chromatography. Hydroxyl-directed Simmons-Smith cyclopropanation (see Section 1.6.1.5.1.2.) provides intermediates which are thermally decomposed to release the optically pure cyclopropyl ketones 20 and the sulfoximine 19. 

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... 

Three- and four-membered rings are versatile intermediates for further transformation. Tsutomu Katsuki of Kyushu University developed Angew. Chem. Int. Ed. 2008, 47, 2450) an elegant Al(salalen) catalyst for the enantioselective Simmons-Smith cyclopropanation of allylic alcohols such as 3. Kazuaki Ishihara of Nagoya University found J. Am. Chem. Soc. 2007,129, 8930) chiral amine salts that effected enantioselective 2-1-2 cycloaddition of a-acyloxyacroleins such as 5 to alkenes to give the cyclobutane 7 with high enantio- and diastereocontrol. 

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