Cyclopropanations of enol ethers

For cyclopropanation of enol ethers with in situ-generated acyloxycarbene complexes of chromium and in the absence of CO, see reference [10a]... 

Reipig (39,40), Pfaltz (41), and Andersson and their co-workers (42) independently showed that these catalysts are capable of effecting the selective cyclopropanation of enol ethers and enolsilanes. Methyl vinyl ketone and acetophenone enolsilanes provide high selectivities in the cyclopropane products, but both isomers are formed equally. The trisubstituted dihydropyran 65 leads to cyclopropane adducts in high diastereoselectivities and enantioselectivities using 55c CuOTf as catalyst. 

In cyclopropanations with electrophilic carbene complexes, yields of cyclopropanes tend to improve with increasing electron density of the alkene. As illustrated by the examples in Table 3.5, cyclopropanations of enol ethers with aryldiazomethanes often proceed in high yields. Simple alkyl-substituted olefins are, however, more difficult to cyclopropanate with diazoalkanes. A few examples of the cyclopropanation of enamines with diazoalkanes have been reported [650]. 

The oxidative ring opening of 3-oxabicyclo[4.1.0]hept-4-enes, formed by the intramolecular Pt(ll)-catalyzed cyclopropanation of enol ethers by alkynes, gives oxepane derivatives. Alternatively, the acid-catalyzed opening of the cyclopropane ring leads to dihydrobenzofurans or 3,4-dihydro-2//-chrorncncs <20040L3191>. 

Diastereoselective cyclopropanation of enol ethers preparation of cyclopropanol derivatives27 ... 

Enol ethers may also be cyclopropanated using zinc carbenoids stereoselectively. Furukawa cyclopropanation of enol ether 32 proceeds with high stereoselection, and the obtained cyclopropyl ether 33 can be easily transformed into the enantiomerically pure cyclopropyl alcohol 35 [30]. In this case, high stereoselectivity is achieved by employing the chiral diol 36, which is not commercially available. Using the commercially available enantiopure diol 37, the level of stereoselectivity is significantly lower (Scheme 7). 

Cyclopropanation of enol ethers, for example the conversion of 399 - 400, proceeds especially easy under Simmons-Smith conditions. This reaction offers additional options for the synthetic utilization of carbonyl compounds capable of forming enol ethers. Some of them will be considered later in this chapter (see Section 2.23.2). 

Rhodium-catalyzed cyclopentene formation has been observed in cyclopropanations of enol ethers 8 and found to depend on the nature of the ligand and the ester of the diazo compound 9 42,43 Cyclopentenes 10 were isolated exclusively with 2,6-di-ter -butyl-4-methylphenyl esters. 

Lewis acid catalysis of the vinylcyclopropane rearrangement has been reported for vinylcy-clopropane 3, a key intermediate in the synthesis of the plant hormone antheridogen-An. Most recently, a report has appeared describing a highly stereoselective, diethylaluminum chloride promoted rearrangement of vinylcyclopropanes 5 to cyclopentenes 6. The cyclopen tenes appear to be formed directly, in some cases as a consequence of the rhodium-promoted cyclopropanation of enol ethers (see Section 2.4.3.1.3.). ... 

The groups of de Meijere and Kostikov utilized the Bamford-Stevens reaction whilst demonstrating the dirhodium(II) tetraacetate catalyzed (chlorovinyl)cyclopropanation of enol ethers and dienol ethers. The resulting vinylcyclopropanes 17 play an important role as precursors to cyclopentenes en route to cyclopentanoid natural products."... 

Considering the above-mentioned facts, according to which simple diazoketones yield dihydrofurans with ketene acetals but cyclopropanes with enol ethers, one exports an interlink between these clear-cut alternatives to exist, i.e. substrates from which both cyclopropanes and dihydrofurans result. In fact, providing an enol ether with a cation-stabilizing substituent in the a-position creates such a situation The Rh2(OAc)4-catalyzed decomposition of -diazoacetophenone in the presence of ethyl vinyl ether produces mainly cyclopropane 82 (R=H), but a small amount of dihydro-... 

Ring expansion (7, 153-154). Details are available for expansion of cyclohexanone to 2-cycloheptenone via cyclopropanation of enol silyl ethers (equation 1). The report includes six other examples of this method yields range from 80 to 98%. In all cases the more highly substituted C C bond of the cyclopropane ring is cleaved by FeCI,.1... 

Thermolysis of ethyl diazopyruvate (136) in the presence of enol ethers and bis(acetylacetonato) copper(II) catalyst did not lead to cyclopropane formation but instead a dihydrofuran (140) was generated (equation 33) . 

The results of a series of reactions of Fischer carbene complexes with enynes are summarized in Tables 1 and 2. Cyclopropane synthesis is accomplished in the alkoxy series (Y = OMe) by the generation of a mixture of geometric isomers of enol ethers, whereas in the dialkyl-amino series, ketones are directly obtained after hydrolysis of the enamines. Higher yields have been obtained using the amino analog pentacarbonyl(l-pyrrolidinoethylidene)chromium [Y = N(CH2)J. - ... 

D.ii. Addition to Aromatic Derivatives. Aromatic compounds also react with carbenes, but ring expansion usually follows the initial cyclopropanation. In a typical example, 2-methoxynaphthalene (373) reacted with dichlorocarbene to give 374, and subsequent ring expansion gave 375, 99 which is a general reaction of enol ethers, which give either unsaturated acetals or unsaturated carbonyls. oo... 

Vinylcyclopropanols have been prepared by the addition of alkenyl Grignard reagents to a variety of cyclopropanone equivalents. Upon treatment with acid, the vinylcyclopropanols rearrange to o-substituted cyclobutanones. Alternatively, a variety of o-heteroatom-substituted cyclopropyl lithium reagents have been developed. These react with aldehydes and ketones to afford cyclopropylcarbinols which also rearrange to cyclobutanones under acid catalysis.Lastly, vinylcyclopropanols and cyclopropylcarbinols have been prepared by the cyclopropanation of enol silyl ethers and allylic alcohols. 

Cyclopropanation of enol sttyl ethers. Cyclopropanation of these substrates with the Simmons-Smith reagent has been reported by several laboratories (4, 588-589). Cyclopropanation can also be effected with diethylzinc-methylene iodide in ether or in n-pentane under controlled conditions (70-80% yields). This reagent can also be used to convert cyclic enol silyl ethers (1) to spiro ethers... 

Boronic acids and their derivatives are very popular as components of chiral Lewis acids and promoters for various reaction processes [481]. Indeed, the chiral acyloxyb-oranes and the oxazaborolidines (Section 1.2.3.5) described in Chapter 11 made a mark in organic synthesis. Recently, Ryu and Corey extended the apphcation of chiral oxaborolidinium catalysts to the cyanosilylation of aldehydes [482]. Chiral diaz-aborohdine salts were evaluated in the enantioselective protonation of enol ethers [145]. Likewise, a tartramide-derived dioxaborolane is key as a chiral promoter in the asymmetric cyclopropanation of allyhc alcohols [483]. More examples and details on the applications of boronic add derivatives as reaction promoters and catalysts are provided in Chapter 10. 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Tab. 3.4 Cyclopropanation of the chiral enol ether 89 under Simmons-Smith conditions...

Tab. 3.5 Cyclopropanation of the chiral enol ethers 92-95 under Furukawa conditions...

The Simmons-Smith cyclopropanation method has also found application for the a-methylation of ketones via an intermediate cyclopropane. The starting ketone—e.g. cyclohexanone 9—is first converted into an enol ether 10. Cyclopropanation of 10 leads to an alkoxynorcarane 11, which on regioselective hydrolytic cleavage of the three-membered ring leads to the semiketal 12 as intermediate, and finally yields the a-methylated ketone 13 ... 

The Simmons-Smith reaction has been used as the basis of a method for the indirect a methylation of a ketone. The ketone (illustrated for cyclohexanone) is first converted to an enol ether, an enamine (16-12) or silyl enol ether (12-22) and cyclopropanation via the Simmons-Smith reaction is followed by hydrolysis to give a methylated ketone. A related procedure using diethylzinc and diiodomethane allows ketones to be chain extended by one carbon. In another variation, phenols can be ortho methylated in one laboratory step, by treatment with Et2Zn and... 

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