1 - Alkoxy-1 -siloxycyclopropanes

In 1977, an article from the authors laboratories [9] reported an TiCV mediated coupling reaction of 1-alkoxy-l-siloxy-cyclopropane with aldehydes (Scheme 1), in which the intermediate formation of a titanium homoenolate (path b) was postulated instead of a then-more-likely Friedel-Crafts-like mechanism (path a). This finding some years later led to the isolation of the first stable metal homoenolate [10] that exhibits considerable nucleophilic reactivity toward (external) electrophiles. Although the metal-carbon bond in this titanium complex is essentially covalent, such titanium species underwent ready nucleophilic addition onto carbonyl compounds to give 4-hydroxy esters in good yield. Since then a number of characterizable metal homoenolates have been prepared from siloxycyclopropanes [11], The repertoire of metal homoenolate reactions now covers most of the standard reaction types ranging from simple... 

The carbenoid from Et2Zn/CH2I2 [17], particularly when generated in the presence of oxygen [18], is more reactive than the conventional Simmons-Smith reagents. The milder conditions required are suitable for the preparation of 1-[16, 19] or 2-alkoxy-l-siloxycyclopropanes [20], which are generally more sensitive than the parent alkyl substituted siloxycyclopropanes (Table 2). Cyclopropanation of silyl ketene acetals is not completely stereospecific, since isomerization of the double bond in the starting material competes with the cyclopropanation [19]. 

The common Lewis acids in this group, A1C13 and BX3, do not form metal homoenolates in their reaction with siloxycyclopropanes, only GaCl3 reacts with 1-alkoxy-l-siloxycyclopropanes 1 to give propionate homoenolates [11]. 

Application of this ring enlargement and oxidation procedure to 2-alkoxy-l-siloxycyclopropanes incorporated in a large ring provides macrocyclic diketones which act as potent chelating agents for metal cations [50]. 

There are a few points to be addressed in order to understand the mechanism of homoenolate formation. Several lines of experimental evidence for the reaction of 1-alkoxy-l-siloxycyclopropanes have provided insights into the nature of the metal interacting with the siloxycyclopropane. 

Heterosubstituted cyclopropanes can be synthesized from appropriate olefins and car-benes. Since cyclopropane resembles olefins in its reactivity and is thus an electron-rich car bo-cycle (p. 76ft). it forms complexes with Lewis acids, e.g. TiCL, and is thereby destabilized This effect is even more pronounced in cydopropanone ketals. If one of the alcohols forming the ketal is a silanol, the ketal is stable and distillable. The O—Si-bond is cleaved by TiCl4 and a d3-reagent is formed. This reacts with a -reagents, e.g. aldehydes or ketals. Various 4-substituted carboxylic esters are available from 1-alkoxy-l-siloxycyclopropanes in this way (E. Nakamura, 1977). If one starts with l-bromo-2-methoxycyclopropanes, the bromine can be selectively substituted by lithium. Subsequent treatment of this reagent with carbonyl compounds yields (2-methoxycyclopropyl)methanols, which can be transformed to /7,y-unsaturated aldehydes (E.J. Corey, 1975B). 

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... 

Again, much efficiency was gained by switching from alkoxy to siloxycyclopropanes . Dibromocarbene addition to silyl enol ethers generates cyclopropanes which open to a-bromo a,j5-unsaturated carbonyl compounds on thermolysis or treatment with acid in methanol (equation 137) . It has been shown that this homologation process also works for siloxycyclopropanes obtained by addition of other carbenoids (equation and that it is useful for terpene preparation . ... 

TMS-Cl or TMS-I, formed in situ, worics as the promoter in addition reactions of zinc homoenolates ((3-metallocarbonyl compounds), generated from 1-alkoxy-l-siloxycyclopropanes and ZnXz (equation 7). No reaction t es place with the purified zinc homoenolates. In contrast, titanium homoenolates are reactive enough to add to aldehydes in the absence of the Lewis acid promoter.Related reactions of zinc esters with aldehydes in the presence of (lVO)3TiCl have been reported (equation 8). ... 

Ring opening is not observed in the reaction of 1-alkoxy-l-siloxycyclopropanes with phosphorus tribromide at 20 "C, which yields the 1-bromo-substituted alkoxycyclopropanes without ring opening. 

Table 8. /1-Trichlorostannyl Carbonyl Compounds by Tin(IV)-Induced Cleavage of 1-Siloxycyclo-propanes and 1-Alkoxy-l-siloxycyclopropanes...

The palladium-catalyzed reaction of 1-alkoxy-l-siloxycyclopropanes with carbon monoxide gives 1,4,7-tricarbonyl compounds in good yield. The reaction is rationalized by formation of a /6-palladio ester from the cyclopropane and a palladium(II) salt, which then undergoes... 

Palladium-catalyzed arylative and acylative ring openings (vide supra) can be successfully applied to 1-alkoxy-l-siloxycyclopropanes. Thus, ) -arylated esters and 4-oxo esters, respectively, are synthesized. Yields are generally higher and the reaction conditions milder for doubly oxygen-substituted cyclopropanes than for siloxycyclopropanes. For acylation, the procedure can be extended from aroyl chlorides to aliphatic acyl chlorides and carbon monoxide is no longer necessary for successful acylation. 

Alkoxy-l-siloxycyclopropane, e.g. 30, on treatment with zinc(II) chloride gives a stable zinc homoenolate, that can, for example, be reacted via an intermediate cuprate with enones to afford the Michael addition product.Addition of a palladium catalyst to the zinc species allows for arylation and for vinylation of the homoenolate in good yield. 

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