Chemoselective cyclopropanation

Trimethylsilyloxy-substituted alkenes are by far the most widely used enol ethers because of their straightforward preparation from the corresponding ketones (equation 20)78-82 -pjjg electron-rich character of silyl enol ethers allows for highly chemoselective cyclopropanations in the presence of additional double bonds (eqnation 21). ... 

The use of stoichiometric ruthenium-NHC complexes generated in situ from [Ruljd-COCKp-cymene)], an imidazohnm salt [4] or an imidizol(idin)ium-2-carboxylate [4] has been applied in the cyclopropanation of styrene 5 with ethyl diazoacetate (EDA) 6 (Scheme 5.2). No base was necessary when imidazolium-2 carboxylate were employed. The diastereoselectivity was low and the cis/trans ratio was around 50/50 (Table 5.1). Although the diastereoselectivity was moderate, the reaction was highly chemoselectivity as possible side reactions (homologation, dimerisation and metathesis) were totally or partially suppressed. 

The different synthetic applications of acceptor-substituted carbene complexes will be discussed in the following sections. The reactions have been ordered according to their mechanism. Because electrophilic carbene complexes can undergo several different types of reaction, elaborate substrates might be transformed with little chemoselectivity. For instance, the phenylalanine-derived diazoamide shown in Figure 4.5 undergoes simultaneous intramolecular C-H insertion into both benzylic positions, intramolecular cyclopropanation of one phenyl group, and hydride abstraction when treated with rhodium(II) acetate. 

Intramolecular C-H bond insertion and ylide formation can compete with cyclopropanation. As shown in Figure 4.21, however, the chemoselectivity of the intermediate carbene complex can sometimes be controlled by the remaining metal-bound ligands [21,990,1075,1081,1223]. 

Cyclopropenation reactions are also effectively catalyzed by dirhodium(II) compounds, and high enantiocontrol has been achieved with the Rh2(MEPY)4 catalysts (Scheme 15.3) [47]. A striking example of the catalyst effect on selectivity is found in the behavior of substrate 25 toward Rh2(5S-MEPY)4 and the more reactive Rh2(4S-IBAZ)4 (Eq. 10) [48]. With the less reactive Rh2(5S-MEPY)4 it preferentially undergoes allyhc cyclopropanation with high chemoselectivity and enantiocontrol. With the more reactive Rh2(4S-IBAZ)4 addition to the carbon-carbon triple bond is favored even though this involves construction of a ten-membered ring. 

Carbenoids derived from the metal catalysed decomposition of diazo compounds undergo various chemical transformations. Control of chemoselectivity by choice of the appropriate catalyst has significantly increased the synthetic viability of catalytic cyclopropanation reactions. Intermolecular reaction of unsaturated alcohols with carbenoids derived from catalytic decomposition of alkyl diazoesters has been reported by Noels and... 

Examples are known where intermolecular carbenoid transformations between diazomalonates or certain diazoketones and appropriate olefins result in competition between formation of cyclopropane and products derived from allylic C—H insertion2-4. For example, catalytic decomposition of ethyl diazopyruvate in the presence of cyclohexene gave the 7-ejco-substituted norcarane 93 together with a small amount of the allylic C—H insertion product 94 (equation 95)142 143. In some cases, e.g. rhodium(II) decomposition of a-diazo-j8-ketoester 95, the major pathway afforded C—H insertion products 96 and 97 with only a small amount of the cyclopropane derivative 98. In contrast, however, when a copper catalyst was employed for this carbenoid transformation, cyclopropane 98 was the dominant product (equation 96)144. The choice of the rhodium(II) catalyst s ligand can also markedly influence the chemoselectivity between cyclopropanation and C—H... 

Thus changing the ligands on dirhodium(II) can provide a switch which, in some cases, can turn competitive transformations on or ofT146. Other examples include the use of dirhodium(II) carboxamides to promote cyclopropanation and suppress aromatic cycloaddition146. For example, catalytic decomposition of diazoketone 105 with dirhodium(II) caprolactamate [Rh2(cap)4] provides only cyclopropanation product 106. In contrast, dirhodium(II) perfluorobutyrate [Rh2(pfb)4] or dirhodium(II)triphenylacetate [Rh2(tpa)4] gave the aromatic cycloaddition product 107 exclusively (equation 100)l46 148. Although we have already seen that rhodium(II) acetate catalysed decomposition of diazoketone 59, which bears both aromatic and olefinic functionalities, afforded stable norcaradiene 60 (equation 70)105, the rhodium(II) acetate catalysed carbenoid transformation within an acyclic system (108) showed no chemoselectivity (equation 101). However, when dirhodi-um(II) carboxamides were employed as catalysts for this type of transformation, only cyclopropanation product 109 was obtained (equation 101). ... 

Carbenoid transformations involving competition between intramolecular cyclopropa-nation and /8-hydride elimination have been investigated149. The chemoselectivity of these catalytic transformations can be effectively controlled by the choice of catalyst. Rhodium(II) trifluoroacetate catalysed decomposition of diazoketone 111 proceeds cleanly to give only enone 112. However, rhodium(II) acetate or bis-(iV-t-butylsalicyladiminato) copper(II) cu(TBs)2 provides exclusively cyclopropanation product 113 (equation 102)149. 

Aviv and Gross developed an interesting insertion reaction of diazo compounds into a secondary amine-hydrogen bond in the presence of Fe-corrole complexes (Scheme 7.8) [12], Competition experiments performed in the presence of an amine and an alkene revealed the N—H-insertion reaction to be much faster than the cyclopropanation of the C=C bond. Apart from this chemoselectivity issue, the reactions are characterized by their very short reaction times most insertion reactions were completed within 1 min at room temperature. Most recently, Woo s group reported on a similar process using commercially available iron tetraphenyl-porphyrin [Fe(TPP)] dichloride [13]. 

A rhodium(I)-.A-heterocyclic carbene complex has brought about a chemoselective decarbonylation, converting a cyclobutanone to the corresponding cyclopropane, while leaving an aldehydic substituent untouched.336... 

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. 

In contrast, the related silyl enol ethers are available by mild selective transformations from carbonyl compounds or other precursors 55). Their stability and that of products derived from these alkenes can easily be regulated by choosing suitable substituents at silicon. Selective cleavage of a Si—O-bond is possible with fluoride reagents under very mild conditions, and this is why cyclopropane ring opening can now be performed with high chemoselectivity. 

The acceptor quality of vinyl ketones liberated from methyl 2-alkenyl 2-siloxycyclo-propanecarboxylates can also be used in cycloaddition reactions. Thus y-oxoester 147 adds smoothly to 2-siIoxybutadien 146 affording a cyclohexene derivative which after desilylation gives the tricarbonyl compound 148. This crucial intermediate can be obtained from vinyl cyclopropane 132 as a precursor of 147 in 72 % overall yield 85). Its chemoselective methylation, lactonization, and dehydration make norbisabolid available — a constituent of the root bark of atalantia monophylla. 

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