Cyclopropanes from alkenes

By application of the Simmons-Smith reaction it is possible to synthesize a cyclopropane from an alkene by formal addition of carbene to the carbon-carbon double bond, without a free carbene being present in the reaction mixture the... 

A simple one-pot preparation of cA-cyclopropanes from y,8-ketoal-kenes using intramolecular alkylation under aqueous conditions was reported. Sequential treatment of y,8-keto alkenes with aqueous NBS in DMSO and then with solid KOH provides cA-cyclopropanes in good overall yields with a diastereoselective excess >99% (Eq. 6.18).38... 

Furthermore, Rhg(CO)16, which can be used advantageously for cyclopropanation of more electron-rich alkenes, furnished only insignificant amounts of cyclopropane from acrylonitrile or ethyl acrylate and ethyl diazoacetate from methacrylonitrile and ethyl diazoacetate, equally low yields of vinyloxazole, cyclopropane and carbene dimers resulted (Scheme 20)145). The use of Rh2(OAc)4 or [Rh(CO)2Cl]2 as catalysts did not change this situation. 

Scheme 4. Mechanism proposed by Evans for the cyclopropanation of alkenes. [Adapted from (35).]...

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

Selected examples of cyclopropanes from non-activated alkenes and in situ produced iodomethylene compounds... 

Calculations [28] on the formation of cyclopropanes from electrophilic Fischer-type carbene complexes and alkenes suggest that this reaction does not generally proceed via metallacyclobutane intermediates. The least-energy pathway for this process starts with electrophilic addition of the carbene carbon atom to the alkene (Figure 1.9). Ring closure occurs by electrophilic attack of the second carbon atom... 

Non-heteroatom-substituted vinylcarbene complexes are readily available from alkynes and Fischer-type carbene complexes. These intermediates can undergo the inter- or intramolecular cyclopropanation reactions of non-activated alkenes. Cyclopropanation of 1,3-butadienes with these intermediates also leads to the formation of cycloheptadienes (Entry 4, Table 2.24). 

There are numerous examples of highly syn diastereoselective cyclopropanation of allylic ethers in the literature, and most of them are alkenes prepared from protected glyc-eraldehyde. Some examples are illustrated in Figure 596.140-143 jjj cases, the... 

Preparation of Cyclopropanes from Alkyl Halides. Alkenes, and Lithium 2,2,6,6-Tetramethylpiperidide... 

A ketone, resulting from the normal oxidation of a secondary alcohol, is obtained along with an alkene, resulting from an opening of the cyclopropane. The secondary product can be explained by the intermediacy of either a chromate ester, or a protonated alcohol. Treatment of the starting alcohol with 10% HC1 leads to a 87% yield of the secondary product, suggesting a mechanism involving PCC as a proton donor. 

These carbene (or alkylidene) complexes are used as either stoichiometric reagents or catalysts for various transformations which are different from those of free carbenes. Reactions involving the carbene complexes of W, Mo, Cr, Re, Ru, Rh, Pd, Ti and Zr are known. Carbene complexes undergo the following transformations (i) alkene metathesis (ii) alkene cyclopropanation (iii) carbonyl alkenation (iv) insertion to C—H, N—H and O—H bonds (v) ylide formation and (vi) dimerization. Their chemoselectivity depends mainly on the metal species and ligands, as discussed in the following sections. 

Acylation of alkenes. Friedel-Crafts acylation (AlCl,) of alkenes suffers from lack of selectivity and low yields. The reaction is markedly improved by use of CHdj-Zn/Cu (3, 255) as catalyst. No cyclopropanation is observed. 

The Simmons-Smith reaction is an efficient and powerful method for synthesizing cyclopropanes from alkenes [43]. Allylic alcohols are reactive and widely used as substrates, whereas a,j8-unsaturated carbonyl compounds are unreactive. In 1988, Ambler and Davies [44] reported the electrophilic addition of methylene to a,/3-unsaturated acyl ligands attached to the chiral-at-metal iron complex. The reaction of the racemic iron complex 60 with diethylzinc and diiodomethane in the presence of ZnCl2 afforded the c/s-cyclopropane derivatives 61a and 61b in 93 % yield in 24 1 ratio (Sch. 24). 

The Bamford-Stevens reaction is the base-catalyzed decomposition of arenesulfonylhydrazones of aldehydes and ketones, leading to the formation of alkenes an or cyclopropanes. There are several important general reviews in this area of organic synthesis. Since the reactions are mostly carried out either in protic or in aprotic solvents, the reaction types are divided into the protic and aprotic Bamford-Stevens processes. This section reviews recent examples in the synthesis of alkenes and cyclopropanes from arenesulfonylhydrazones, which is closely related to the following Shapiro reaction. 

Table 11. Cyclopropanes from Addition of 9-Fluorenylidene to Acyclic Alkenes... 

Table 13. Cyclopropanes from Addition of 9-Fluorenylidene Derivatives, Generated by Decomposition of the Corresponding 9-Diazo-9i/-fluorene Derivatives, to Alkenes... 

Table 14. Cyclopropanes from Photolysis of Various Diazobenzocycloheptene Derivatives in the Presence of Alkenes... 

Table 15. Cyclopropanes from Polycyclic Diazoarenes and Alkenes... 

Starting from (2-oxoalkylidene)sulfur-5, triacylcyclopropanes are often the dominant products, regardless of the decomposition mode of the sulfonium ylide. . In fact, no example of an efficient alkene cyclopropanation using these synthetic equivalents of oxocar-benes is yet known. The photochemical decomposition (2> 300nm) of (2-oxo-2-phenylethylidene)sulfur-5" in cyclohexene yielded only a minor amount of 7-benzoyl-bicyclo[4.1.0]heptane (2, 5%) in addition to tranj-l,2,3-tribenzoylcyclopropane (3, 40%), acetophenone (37%), bicyclohex-2-enyl (38%), and propiophenone (3%). In an inert solvent (benzene, chloroform) without an additional trapping reagent,, 2,3-tribenzoylcyclo-... 

Table 5. Cyclopropanes from Diazocarbonyl Compounds and Electron-Deficient Alkenes ...

With the chiral bis(semicorrinato)copper(II) complex 9 developed by Pfaltz, enan-tioselectivities for cyclopropanes from monosubstituted alkenes are significantly higher than with Aratani s catalysts. Again, enantiocontrol can be increased by utilizing bulky diazoacetic esters (see Houben-Weyl, Vol.E19b, plll2). For menthyl diazoacetate and alkenes such as styrene, hept-l-ene, buta-1,3-diene and penta-1,3-diene, de values of 92-97% have been obtained. However, cyclopropanation of 1,2-disubstituted and trisubstituted alkenes occurs with lower chemical yield and asymmetric induction when catalyst 9 rather than 7 (R = Me) was used. ... 

This method also allows the preparation of cyclopropanes from electrophilic alkenes, usually in good yields, e.g. preparation of 6. ... 

Historically, potassium /er/-butoxide was the first base used for the preparation of 1,1-dibromo-cyclopropanes from bromoform and an alkene. Since generation and cycloaddition of dibromo-carbene to alkenes proceeds rapidly, this method is still in laboratory practice. 

Tosylhydrazones of aliphatic aldehydes and ketones react with a base in an aprotic solvent at 90-180 C to give diazo compounds which undergo thermal decomposition with loss of nitrogen to yield alkenes derived from hydrogen migration and cyclopropanes from intramolecular insertion. In proton donor solvents decomposition of y-tosylhydrazones by base occurs primarily by a cationic mechanism involving diazonium and/or carbenium ion intermediates. 

Besides rearrangements, ligand exchange, formation of alkanes, alkenes and other products, release of cyclopropanes is one of the most important reactions of metallacyclobutanes. Of course, this latter reaction is only useful in cyclopropane synthesis if the product is not identical with the starting material used to form the metallacyclobutane. Nevertheless, the discovery of a complex formed from hexachloroplatinic acid and cyclopropane and later structural elucidations have initiated intensive investigations on the conversion of cyclopropanes to metallacyclobutanes and release of cyclopropanes from the latter. These results have been thoroughly discussed in several reviews. " Therefore in this section only some general aspects of cyclopropane formation from metallacyclobutanes and selected synthetically useful methods are discussed. 

Decomplexation of cyclopropanes from metallacyclobutanes is facilitated thermally or photo-chemically as well as by numerous reagents such as phosphanes, alkenes, cyanides, or oxidants [Ij, Oj, Ce(IV), etc.]. Depending on the method used, striking differences in product selectivities are observed, even with respect to stereochemical results. Thus, decomplexation of trans-1,2-... 

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