Cyclopropanation of allylic alcohols

O Connor, S.P. Catalytic, Enantioselective Cyclopropanation of Allylic Alcohols PhD Thesis, University of Illinois, Urbana-Champaign, 1993. 

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

Copper(II) triflate is quite inefficient in promoting cyclopropanation of allyl alcohol, and the use of f-butyl diazoacetate [164/(165+166) = 97/3%] brought no improvement over ethyl diazoacetate (67/6 %)162). If, however, copper(I) triflate was the catalyst, cyclopropanation with ethyl diazoacetate increased to 30% at the expense of O/H insertion (55%). As has already been discussed in Sect. 2.2.1, competitive coordination-type and carbenoid mechanisms may be involved in cyclopropanation with copper catalysts, and the ability of Cu(I) to coordinate efficiently with olefins may enhance this reaction in the intramolecular competition with O/H insertion. 

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

A. Cyclopropanation of Allylic Alcohols with Magnesium Carbenoids. . . 722... 

The Simmons-Smith-type cyclopropanation of olefins is one of the most well-known reactions of carbenes and carbenoids. However, cyclopropanation of simple olefins with magnesium carbenoids is usually very difficult and only cyclopropanation of allylic alcohols was reported. Thus, treatment of allylic alcohols (23) in CH2CI2 at —70°C with i -PrMgCl and diiodomethane for 48 to 60 h afforded cyclopropanes in up to 82% yield as a mixture of syn- and and-isomers. In this reaction, 5yn-isomers were mainly or exclusively obtained (synianti = 5 1-400 1) (equation 10). 

The cyclopropanation of allylic alcohols in which a non-Lewis basic stereogenic center is located at the other allylic position does not generally proceed with high enantiocontroF. One interesting exception is the cyclopropanation of E-vinylcyclopropanes, which produced the anti isomer with high induction (equation 69) . 

The cyclopropanation of alkenes using external stoichiometric chiral additives can be divided according to their general mechanistic scheme into two classes. The enantios-elective cyclopropanation of allylic alcohols, in which a pre-association between the corresponding zinc alkoxide and the zinc reagent probably takes place, constitutes the first class. The second class involves the enantioselective cyclopropanation of unfunctionalized alkenes. The latter implies that there will be no association between the reagent and the alkene through alkoxide formation. 

V,A,iV, Ai -Tetraethyl-l,l -bi-2-naphthol-3,3 -dicarboxamide (20) has been shown by KatsuTi and coworkers to be quite effective as a stoichiometric additive in the cyclopropanation of allylic alcohols (equation 89) . The best enantioselectivities were obtained with aryl-substituted allylic alcohols however, 6 equivalents of diethylzme were needed. 

Enantioselective cyclopropanation of allylic alcohols using chiral catalysts... 

There is only one example of a catalytic enantioselective cyclopropanation of allylic alcohols using an electron withdrawing chiral disulfonamide 19 as a chiral ligand (Protocol 6).33 Stoichiometric highly enantioselective cyclo-propanations of allylic alcohols are reported using a chiral diethyl tartrate34 and a chiral tartamide.35... 

Preparation of the Zn(CH2l)2 DME complex enantioselective cyclopropanation of allylic alcohols with chiral ligand... 

Recently, many efforts have focused on the development of the enantioselective (iodomethyl)zinc-mediated cyclopropanation of allylic alcohols. Kobayashi and co-workers reported that moderate to good enantioselectivities were observed if a C2-symmetric chiral disulfonamide was added. To reduce the rate of uncatalyzed... 

Denmark et al. studied the effect of zinc iodide on the catalytic, enantioselective cyclopropanation of allylic alcohols with bis(iodomethyl)-zinc as the reagent and a bismethanesulfonamide as the catalyst 17]. They found significant rate enhancement and an increased enantiomeric excess of the product cyclopropane upon addition of 1 equivalent zinc iodide. Their studies and spectroscopic investigations showed that the Schlenk equilibrium appears to lie far on the left (IZnCHjI). Charette et al. used low temperature - C-NMR spectroscopy to differentiate several zinc-carbenoid species [18]. They also found evidence that in the presence of zinc iodide, bis(iodomethyl)zinc is rapidly converted to (io-domethyOzinc iodide. Solid-state structures of (halomethyl)zinc species have been described by Denmark for a bis(iodomethyl)zinc ether complex (6a) [19] and Charette for an (iodo-methyl)zinc iodide as a complex with 18-crown-6 (6b) [20] (Fig. 2). 

Cyclopropanation of Allylic Alcohols. Simmons-Smith type cyclopropanation of the allylic alcohol 22 in the presence of a catalytic amount of the bis-sulfonamide la leads to formation of the corresponding cyclopropane 23 in high yield and selectivity (eq 6, Table 3). The reaction is rapid (< 1 h) and can be performed at low temperature (either 0 °C or —20 °C). Substrate scope encompasses both di- and tri-substimted allylic alcohols (24 and 26). However, substimtion at the 2 position, as in 28, leads to a drastic decrease in selectivity. The presence of additional oxygenated functionality (30) in the proximity of the alkene also lessens selectivity." The method is limited to the cyclopropanation of allylic alcohols. Other alkene-containing substrates, such as allylic ethers, homo-allylic alcohols and allylic carbamates, do not react with high selectivity. 

Table 8. Cyclopropanation of allylic alcohols with the aluminum catalyst 133 (Ar = Ph).

The chiral version of the Simmons-Smith reaction requires the presence of proper ligands for the organozinc reagent. Representatives are 99, 100, 101 " for cyclopropanation of allylic alcohols. Enals undergo diastereoselective cyclopropanation (de >99%) via acetals with (+)-phenyl exo,ex o-2,3-dihydroxybomane-10-sulfonate. ... 

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 A, A -bis(arenesulfonyl)cyclohexane-1,2-diamines used as chiral controllers (see also Houben-Weyl, Vol. E21, pp 1327, 3895) can also be employed as their aluminum complexes to catalyze the cyclopropanation of allylic alcohols with diethylzinc and diiodomethane. ° The bis(sulfonamide)aluminum complex was first prepared in situ in 1,2-dichloroethane and after removal of the solvent in vacuo, cyclopropanation was carried out in dichloromethane at — 20 °C. The enantioselectivities are similar to those obtained with the chiral zinc catalyst described above. However, the most characteristic feature of the chiral aluminum complex catalyzed reaction is that no decrease in the enantioselectivity was observed even at a higher concentration. An electron-withdrawing group on the benzene ring of the sulfonamide or the... 

A much higher and more efficient chiral version (>90%) of the cyclopropanation of allylic alcohols is obtained by using the amphoteric bifunctional ligand (R,R)-93 prepared from commercially available (+)-(/ ,7 )-At,TV,A, A -tetramethyltartaric acid diamide and butyl-boronic acid. The dioxyborolane chiral ligand proved to be extremely effective with several types of substituted allylic alcohols 92. The chiral ligand 93 can easily be removed and recovered (> 80%) by a simple aqueous extraction of the organic layer after the reaction. 

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. 

Optimization of the reaction protocol and the study of the effect of promoter structure on selectivityin the catalytic enantioselective cyclopropanation with bis(halomethyl)zinc reagents have been reported recently. Prior formation of a zinc alkoxide and the use of added zinc iodide are critical for efficient catalytic enantioselective cyclopropanation of allylic alcohols using chiral bis(sulfonamides), the simple A7,iV -dimesylcyclohexane-l,2-diamine being the most effective in terms of rate and enantioselectivity. 

The zinc metal in the Simmons-Smith reaction was replaced by samarium for the cyclopropanation of allylic alcohols with chloroiodomethane. High yields of cyclopropanes, often with high diastereoselectivities, were obtained using samarium amalgam/diiodomethane. Cyclo-hex-2-enol (115a) gave exclusively s y -bicyclo[4.1.0]heptan-2-ol (116a), no traces of the anti-... 

Cyclopropanation of Allylic Alcohols Using Samarium/Dihalomethane General Procedure ... 

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