Enol ethers, addition carbenes

Alkenes are scavengers that are able to differentiate between carbenes (cycloaddition) and carbocations (electrophilic addition). The reactions of phenyl-carbene (117) with equimolar mixtures of methanol and alkenes afforded phenylcyclopropanes (120) and benzyl methyl ether (121) as the major products (Scheme 24).51 Electrophilic addition of the benzyl cation (118) to alkenes, leading to 122 and 123 by way of 119, was a minor route (ca. 6%). Isobutene and enol ethers gave similar results. The overall contribution of 118 must be more than 6% as (part of) the ether 121 also originates from 118. Alcohols and enol ethers react with diarylcarbenium ions at about the same rates (ca. 109 M-1 s-1), somewhat faster than alkenes (ca. 108 M-1 s-1).52 By extrapolation, diffusion-controlled rates and indiscriminate reactions are expected for the free (solvated) benzyl cation (118). In support of this notion, the product distributions in Scheme 24 only respond slightly to the nature of the n bond (alkene vs. enol ether). The formation of free benzyl cations from phenylcarbene and methanol is thus estimated to be in the range of 10-15%. However, the major route to the benzyl ether 121, whether by ion-pair collapse or by way of an ylide, cannot be identified. 

In addition to reactions characteristic of carbonyl compounds, Fischer-type carbene complexes undergo a series of transformations which are unique to this class of compounds. These include olefin metathesis [206,265-267] (for the use as metathesis catalysts, see Section 3.2.5.3), alkyne insertion, benzannulation and other types of cyclization reaction. Generally, in most of these reactions electron-rich substrates (e.g. ynamines, enol ethers) react more readily than electron-poor compounds. Because many preparations with this type of complex take place under mild conditions, Fischer-type carbene complexes are being increasingly used for the synthesis [268-272] and modification [103,140,148,273] of sensitive natural products. 

Another access to 1-alkoxy-l-siloxycyclopropanes 5, precursors of substituted cyclopropanone hemiacetals 6, was developed with the addition of carbenes, generated from alkylidene iodides and diethylzinc, to the trimethylsilyl enol ethers of carboxylic... 

Quite recently a modification of the carbene addition reaction has been published and applied to the synthesis of phoracantholide I (11/88) [70]. The silyl enol ether 11/85 prepared from ( )-8-nonanolide underwent addition of chlorocarbene to give the intermediate bicyclic adduct 11/86, which rearranged into an E/Z-mixture of a,/J-unsaturated lactones 11/87 by heating. Phoracantholide I (11/88) was formed by hydrogenation of the latter, Scheme 11/12. 

Dipolar cycloaddition reactions are most commonly applied for the synthesis of five-membered heterocyclic compounds.86 87 [3+2] cycloaddition reactions of transition-metal propargyl complexes have been reviewed.88 Addition of diazomethane to carbene complexes (CO)5Cr= C(OEt)R results in cleavage of the M = C bond with formation of enol ethers H2C = C(OEt)R,3 89 but (l-alkynyl)carbene complexes undergo 1,3-dipolar cycloaddition reactions at the M = C as well as at the C=C bond. Compound lb (M = W, R = Ph) affords a mixture of pyrazole derivatives 61 and 62 with 1 eq diazomethane,90 but compound 62 is obtained as sole... 

Addition of propargylic alcohol to a (l-alkynyl)carbene complex le,f (M = Cr, W) affords the enol ether adduct ( )-158, whose chromium... 

Addition of cyclohexyl isocyanide to enol ether 164 derived from addition of phenol to a (l-alkynyl)carbene complex la results in formation of a... 

Table 9 Ring Expansion of Ketones via Halo Carbene Addition to Silyl Enol Ethers...

Ring expansion of the substituted bicyclo[4.1.0]heptanes 8, formed by addition of chloromethyl-carbene to silyl enol ethers, was accomplished almost equally effectively by refluxing in toluene, or by heating in methanol containing triethylamine. In each case, the crude mixture of cis- and /rani-7-chloro-7-methylbicyclo[4.1. Ojheptanes 8 was used, although it was observed that the traui-isomers, with the chlorine and trimethylsiloxy substituents tram to each other, rearranged more rapidly. 

Chloro-l-methyl-2-siloxycyclopropanes are interesting synthetic intermediates as they are easily cleaved to 2-methyl-substituted a,/8-unsaturated aldehydes or ketones. Addition of chloro(methyl)carbene (carbenoid) to trimethylsilyl enol ethers gives l-chloro-l-methyl-2-tri-methylsiloxycyclopropanes 11,70-72 which are usually rearranged without purification, due to their restricted stability. A few examples are given in Table 5 (see also Houben-Weyl, Vol. E19b, p 1516). 

One of the most widely used methods for the formation of C-glycosides involves electrophilic species derived from the sugar component. Some representative examples, shown in Figure 2.0.1, include oxonium compounds, lactones, enones, carbenes, and enol ethers. Once formed, nucleophiles can be induced to react with these reactive species thus providing tremendous diversity in the types of C-glycosides accessible. This chapter focuses on various approaches made use of in the formation of C-glycosides via the addition of nucleophiles to carbohydrate-derived electrophiles. 

Another side reaction can occur in ylids that bear a heteroatom substituent, decomposition to a carbene intermediate (sec. 13.9.B). Butoxymethyl ylid 516 spontaneously fragmented to triphenylphosphine and carbene 517, for example. This carbene reacted with an additional molecule of the ylid (516) to give the bis(enol)ether (519) via the zwitterion 518. ... 

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... 

From a methodological point of view, it should be pointed out the formation of 51, which is a result of the addition of acetone to an allenylidene ligand. Heteroatom-containing cyclic metal-carbene complexes [24] have been conveniently prepared via metal co-haloacyl, carbamoyl, alkoxycarbonyl, or imido intermediates [25], opening of epoxides by deprotonated Fischer-type carbene complexes [26], and activation of homopropargylic alcohols with low-valent d complexes [27], including ruthenium(II) derivatives [28]. In general, the preparation of unsaturated cyclic carbene complexes requires the previous preparation of functional carbenes to react with P-dicarbonyl derivatives, acrylates, and enol ethers [29]. 

The first step in this scheme is a Michael addition of the nucleophile to the j5-carbon of the alkynyliodonium salt to give the ylide 102. Loss of iodobenzene from 102 gives alkylidenecarbene 103, which rearranges to alkyne 104 in the absence of external traps. This mechanism is experimentally supported by the isolation of cyclic by-products 108 besides the major products, the alkynyl esters 107 in the reaction of alkynyliodonium salt 105 with nucleophiles (equation 67). These cyclic enol ethers are the result of the insertion of the intermediate carbene 106 into the tertiary-8-carbon-hydrogen bond. 

An interesting study reports carbene additions to the androstane enol ether (139). Addition of dibromo- and dichloro-carbene gave the D-homo-a-halo-genoenones (140a) and (140b), respectively. The Simmons-Smith reaction on (139) afforded the l6a,17a-cyclopropyl steroid (141). Whereas treatment of (141) with acid provided the D-homo-derivative (142), reaction with iodine, followed by... 

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