Asymmetric Simmons-Smith reactions

Simmons-Smith reaction. Asymmetric methylene transfer to allyl glycosides containing a free hydroxyl group at C-2 arises from its directing effect. Both /3-l-glucopyranosides and their a-o- analogs have been exploited for the access of chiral cyclopropanes. 

These initial reports demonstrated that a catalytic asymmetric variant of the Simmons-Smith reaction could be developed. Although good yields and selectivities were obtained, the lack of a clear understanding of the origin of activation, the limited structural information on the active species and the absence of a stereochemical model made rational improvements difficult at best. The next... 

Brookhart Liu Organometallics 1989, 8, 1572,J. Am. Chem. Soc. 1991,113, 939 Brookhart Liu Goldman Timmers Williams J. Am. Chem. Soc. 1991, 113, 927 Lowenthal Abiko Masamune Tetrahedron Lett. 1990, 31, 6005 Evans Woerpcl Hinman Faul J. Am. Chem. Soc. 1991, 1/3, 726. For asymmetric Simmons-Smith reactions, sec Mori Arai Yamamoto Tetrahedron 1986, 42, 6447 Mash Nelson Heidt Tetrahedron Lett. 1987, 28, 1865 Sugimura Futagawa Yoshikawa Tai Tetrahedron Lett. 1989, 30, 3807. See also Ojima Clos Bastos, Ref. 232, pp. 6919-6921. 

Asymmetric cyclopropanation of olefins can also be achieved by the Simmons-Smith reaction (231). Reaction of ( )-cinnamyl alcohol and the diiodomethane-diethylzinc mixed reagent in the presence of a small amount of a chiral sulfonamide gives the cyclopropylcarbinol in up to 75% ee (Scheme 97) (232a). ( )-Cinnamyl alcohol can be cyclopro-... 

The synthesis of substituted glutamic acid analogues has been pursued by many routest94-106 using asymmetric alkylation, Simmons-Smith reactions, Diels-Alder reactions, and nickel complexes of glycine or alanine equivalents. 

Scheme 24 Synthesis of a y,y-Disubstituted Glutamic Acid via an Asymmetric Simmons-Smith Reaction 97-1081...

The methods for stereocontrolled synthesis of cyclopropylboronic esters have been studied (Scheme 29). The palladium-catalyzed reaction of diazoalkanes (method A), Simmons-Smith reaction (method B), or asymmetric Simmons-Smith reaction using chiral diamines such as 270 (method C) for chiral or achiral 1-alkenylboronic esters... 

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... 

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... 

The first asymmetric Simmons-Smith reaction with a chiral Lewis acid catalyst was introduced in 1994 by Charette and Juteau and featured a chiral boron Lewis acid prepared from tartaric acid [32]. Although this process resulted in excellent enantioselec-tivity, it would not turnover, i.e. the yield was less than 10 %. In the same year Imai, Takahashi and Kobayashi introduced a chiral aluminum Lewis acid that would catalyze the cyclopropanation of allylic aleohols with significant turnover numbers but their system did not lead to asymmetric induction as high as that resulting from the dioxaborolane catalyst [33]. The catalyst is prepared from the bis-sulfonamide 132... 

The scope of the reaction was examined with a catalyst prepared from the benzene sulfonamide and DIBAL, because it was found that essentially the same induction could be obtained as with those obtained from tri-/so-butyl aluminum. Two years earlier the authors had reported that this Simmons-Smith reaction could also be catalyzed by the aluminum-free sulfonamide 132 (optimum with Ar = /7-NO2C6H4) the induction obtained is listed in the far right column of Table 8 [34]. It was proposed that a zinc complex of 132 is generated in-situ. Surprisingly, with the exception of the silyl-substituted allyl alcohol (the last entry in the table) [35], almost identical asymmetric induction obtained by use of the aluminum-containing and aluminum-free catalysts. The main advantage of the diazaaluminolidine catalyst is that it is apparently more soluble than the aluminum-free bis-sulfonamide catalyst, with the result that a tenfold increase in concentration (0.1 m) can be used this might explain the increased rate observed for the diazaaluminolidine catalyst. Finally, it has recently been reported that a catalyst formed from the Ci symmetrical sulfonamide 135 and DIBAL will induce the formation of 131 from cinnamyl alcohol in 68 % ee [36]. 

An asymmetric Simmons-Smith reaction was reported by Kang et al. [18]. The reaction of (3-D-fructopyranoside 13 with a,(3-unsaturated aldehydes gave enrfo-acetals 14 along with exo-isomers 15 in a ratio of about 1.5 1. The enrfo-acetals afforded the best selectivity, typically giving (2/f,3/f)-hydroxymethyl cyclopropanes 17 with up to 85% ee. It should be noted that the corresponding exo-acetals 15 underwent the cyclopropanation reaction with lower stereoselectivity. In these cases, the group cannot effectively block either side of the alkene in contrast to the endo-isomer [18] (Scheme 10.3). 

Normally the chiral auxiliaries are introduced and removed in the asymmetric synthesis of Simmons-Smith reactions of allylic alcohols to provide mostly /rani-disubstituted cyclopropanes. Stereoselective syntheses of c -disubstituted cyclopropanes are difficult to achieve. Starting from (Z)-3-phenylprop-2-en-l-ol (80a) and (Z)-6-phenylhex-2-en-l-ol (80b), the corresponding c -disubstituted cyclopropanes 81a and 81b were prepared by first treating them with diethylzinc followed by diethyl (- -)-(/ ,7 )-tartrate (DET). A zinc-bridged intermediate is assumed to be formed first. This is subsequently treated with diethylzine and diiodomethane to give the products 81. The reaction conducted at — 12 "C gave the cyclopropanated products 81a and 81b with 70 and 81% ee, respectively.This method has the advantages that the introduction of the chiral auxiliary to the substrate and its removal are not neccessary and that both cis- and trans-disubstituted cyclopropanes could be prepared from (Z)- and ( )-allylic alcohols, repectively. 

Cycloadditions. Asymmetric Simmons-Smith reaction of allylic alcohols performed in the presence of an aluminum complex of the salen 127 has been reported. ... 

Compund 78 is among the new transition metal catalysts that have found good use in the decomposition of diazo compounds and delivery of the metal carbenoids to alkenes." Iminodiazaphospholidine (79) possesses a stereogenic phosphorus center and its applicability to effect asymmetric cyclopropanation" is now known. The Zn chelate of 80 is effective for the Simmons-Smith reaction of allylic alcohols. ... 

Asymmetric induction is possible in the Simmons-Smith reaction if a suitable auxiliary is used, or if the chirality is built in via a chiral template precursor (sec. 10.9). When 418 was prepared from diethyl tartrate. 

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. ... 

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