Allylic alcohol asymmetric cyclopropanation

Scheme 5-66 shows another example of chiral bis(sulfonamide) 205 catalyzed asymmetric cyclopropanation of allylic alcohol.119... 

Enantiopure allylic alcohols are employed widely as building blocks for asymmetric synthesis, and particularly as substrates for various diasteroselective allcene functionalization reactions such as cyclopropanation and epoxidation directed by the hydroxyl group [129]. 

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... 

Kobayashi et al. successfully performed asymmetric cyclopropanation using substoichio-metric amounts of catalyst 45 (Scheme 9). [32] The levels of enantioselectivity achieved are in the 70-90 % range. Both, E- and Z-allylic alcohols are readily converted. Vinylstannanes 46 are also appropriate substrates. The resulting enantio-merically pure cyclopropanated stannanes hold great synthetic potential [33]. Thus, the cyclopropanated stannane 48 can be converted into the substituted cyclopropane 49 after successful tin-lithium exchange and electrophilic substitution. 

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. ... 

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. 

However, this asymmetric cyclopropanation of allylic alcohols can be used only up to 1 mmol equivalent. When run on a larger scale, e.g. 8 mmol, a violent explosion of the reaction mixture was observed. Accordingly, the authors have improved the procedure by adding the bis(iod-omethyl)zinc reagent as its 1,2-dimethoxyethane complex in dichloromethane. The cyclo-propanations were safely carried out on > 1 mmol scale with 93% ee and > 98% yield, e.g. cyclopropanation to give 95. The chiral alcohol and butylboronic acid could be recovered and used again. 

Olefins are very important industrial raw materials, and much effort has been devoted toward using them as substrates in asymmetric synthesis [811, 812, 853], The industrial synthesis of nonracemic a-aminoacids by catalytic hydrogenation was ore of the first important uses of olefins in asymmetric synthesis [859], Today, the Sharpless epoxidation of allylic alcohols [807, 808, 809] is one of the most popular methods in asymmetric synthesis. The importance of pyrethrinoid pesticides, bearing a cyclopropane skeleton, justifies the efforts devoted to the asymmetric synthesis of cyclopropanes from alkenes [811,812, 937],... 

Scheme 6.28. Asymmetric cyclopropanation of allylic alcohols (a) Using a glucose-derived auxiliary [106] (b) A cyclohexane diol auxiliary [107].

Conformational considerations restrict the number of possible transition state geometries in intramolecular cyclopropanations, which are quite selective, as shown by the examples from Doyle, Martin, and Muller illustrated in Scheme 6.38a [140,141]. Intramolecular cyclopropanation of diazo esters of chiral allylic alcohols are subject to double asymmetric induction, as shown by the series of examples in Scheme 6.38b. For all of these substrates, the exo product is slightly preferred when cyclopropanation is mediated by an achiral catalyst [142], but this selectivity is reversed dramatically when the S ester is allowed to react with the 5-S-MEPY catalyst. This pronounced endo selectivity persists for both the E and the Z-alkenes, although it is higher for the Z alkenes. Note also that when the chirality sense of the substrate and the catalyst are mismatched (5 substrate and R catalyst), the endo selectivities are low, unless R1/R2 are trimethylsilyl. For the matched case of double asymmetric induction, the same features that cause the endo selectivity can be used... 

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. ... 

An allylic alcohol may undergo an asymmetric cyclopropanation by attachment of a chiral ligand (e.g., a tartrate ester) to the derived zinc alkoxide. 

Asymmetric cyclopropanation reactions have been developed by using diiodomethane and diethyl zinc in the presence of a chiral Lewis acid. A particularly effective chiral Lewis acid, introduced by Charette, is the dioxaborolane 112, which induces high levels of optical purity in the resultant cyclopropanes derived from allylic alcohols (4.90). This methodology has been used in natural product synthesis, such as in the preparation of the antifungal agent FR-900848 (4.91). ... 

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