Asymmetric cyclopropanation, of allylic alcohols

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

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. 

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

Scheme 7.47 Asymmetric cyclopropanation of allylic alcohols using complex 78.

Titanium isopropoxide-TADDOLate, 99, system was used by Charette et al. for asymmetric cyclopropanation of allylic alcohols, 100, (reaction 7.18) with acceptable yield and enantioselectivity [68]. 

High enantioselectivities are obtained using N,N,N, N -tetramethyltartaric acid diamide-derived boronate ester 32 in combination with bis(iodomethyl)zinc for asymmetric cyclopropanation of allylic alcohols. Various chiral, non-racemic cyclopropyl-methanols can be obtained in enantiomeric excesses of 91-94%. This methodology has been extended with success to the cyclopropanation of unconjugated and conjugated polyenes and homoallylic alcohols (Equation 47) [45]. 

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. 

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],... 

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. ... 

The use of catalytic amounts of a chiral source is important to improve the efficiency of asymmetric induction. Charette and coworkers used 10mol% of chiral phosphoric acid 116, derived from a binaphthol derivative, and achieved catalytic asymmetric cyclopropanation to form allylic alcohols 117 (Scheme 1.57) [96]. Walsh and cowoikers reported that the efficient asymmetric synthesis of cyclopropylmethyl alcohol... 

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