Siloxycyclopropanes, synthesis

A major advantage of the sequence presented here is that the aldehyde group is protected at the siloxycyclopropane stage, which allows convenient storage of this stable intermediate. Of equal importance is the valuable carbanion chemistry that can be carried out a to the ester function. Efficient substitution can be achieved by deprotonation with LDA and subsequent reaction with electrophiles.12-13-6 This process makes several a-substituted [1-formyl esters available. Other ring opening variants of siloxycyclopropanes - mostly as one-pot-procedures - are contained in Scheme I. They underscore the high versatility of these intermediates for the synthesis of valuable compounds.6 Chiral formyl esters (see Table, entries 2-5) are of special... 

The recent surge of interests in metal homoenolate chemistry has been stimulated by the recognition that the siloxycyclopropane route can afford novel reactive homoenolate species that are stable enough for isolation, purification, and characterization. The stability of such homoenolates crucially depends on the subtle balance of nucleophilic and electrophilic reactivity of the two reactive sites in the molecule. Naturally, homoenolates with metal-carbon bonds that are too stable do not serve as nucleophiles in organic synthesis. 

Although alkylations of enolates with a-halo ester compounds are quite effective in singular cases, these reactions often proceed with poor yield and selectivity. Therefore the siloxycyclopropane route is to be considered even for large scale preparations of relatively simple y-oxoesters. Synthesis of rather sensitive formyl esters (entries 9, 13, 16, 17) or the stereoselective generation of /ranj-substituted cyclic y-oxoesters as mentioned above can hardly be achieved with comparable efficiency by other methods. 

The mild cleavage conditions with NEt3 HF, which do not cause epimerization at centers a to the carbonyl group, are essential for an enantioselective synthesis of y-oxoesters using optically active catalysts 641 in the cyclopropanation step. Up to 50 % ee have been obtained so far 65). Improvements should be possible, if the trans/cis-ratio of the siloxycyclopropane can be increased. Formylesters of type 99 are promising building blocks for further transformations (e.g. synthesis of y-butyrolactones). 

Siloxycyclopropane 132 — which is a masked vinyl ketone — has served as test substrate for many in situ transformations. It cleanly reacts with several of O-, N-, and S-nucleophiles under mild acidic or basic conditions leading to polyfunctionalized y-oxoesters 137 (Eq. 55) 83), which for instance can be further converted to y-butyrol-actones, as exemplified by the one-pot-synthesis of 138 76). 

The synthesis of dihydrofuran derivatives such as 177 has been performed to explore scope and limitations of the Lewis acid promoted hydroxyalkylation of siloxycyclopropanes. Table 6 shows that aromatic as well as aliphatic ketones can efficiently be incorporated. Enolization of ketones does not occur and a 1-methyl group at the cyclopropane is no obstacle for the reaction, which now binds the carbonyl compound to a quartemary center with surprisingly high efficiency (entry 5). Albeit there are some restrictions with regard to the substitution pattern of the cyclopropanes, bicyclic siloxycyclopropanes also give good yields (e.g. entry 6 and Eq. 76). Further examples of the tetrahydrofuran synthesis from intermediate y-lactols with... 

Scheme 10. Synthesis of Different Furan(one) Derivatives from a Siloxycyclopropane and Acetone...

Siloxycyclopropanes are known as homoenolate anion equivalents and have been favorably utilized in organic synthesis. Murai, Sonoda, and coworkers found that desi-lylative dimerization of the siloxycyclopropanes occurs on exposure to AgBp4 [26a], The reaction of 54 gives 1,6-diketone 55 in good yield (Sch. 13). The 8-silver ketone 56 is considered to be a key intermediate in the dimerization. The intermediary ver ketone, generated from siloxycyclopropane 57 and AgP, can be successfully trapped with allyl chloride to afford a (5,e-unsaturated ketone 58 [26b]. 

A carbonylation reaction with Ni(CO)4 generating 1,4,7-tricarbonyl compounds has also been published Synthesis of 1,6-dicarbonyl systems via mercury(II) intermediates and radical chain additions to electrophilic olefins has been achieved (equation 70). This sequence constitutes an umpolung if one considers that the carbonyl moiety is masked in siloxycyclopropanes TTireo-juvabione has been synthesized from a methoxycyclo-propane via a mercury(II) salt cleavage/reduction sequence ... 

These epoxides can be converted to vinyl siloxycyclopropanes m high yield by treatment with base and trimethylsilyl chloride. Transformations of these interesting intermediates (see Section VII) into various products are demonstrated in equation 103. Isolation of oxaspiropentanes is not required in a route to cyclobutanones which are formed by straightforward acid workup (equation 104) . These can either be expanded to y-butyrolactones by oxidation or to an enol ester by a-formylation and acid-induced fragmentation. The latter sequence has been utilized in a synthesis of acorenone... 

Basic treatment of siloxycyclopropanes with methanolic sodium hydroxide at room temperature induces desilylation, providing a convenient synthesis of cyclopropanols. 

A similar rearrangement occurs with phenylhalocarbene adducts of alkylsilyl ketene acetals 16/ and with siloxycyclopropanes obtained by addition of other carbenoids. ° The method is useful in terpene synthesis. ° ° ... 

The Cu(acac)2-catalyzed cycloaddition between a TBDMS enol ether and alkyl diazoacetates provides a useful method for the preparation of siloxycyclopropanecarboxylates (eq 44). Since these siloxycyclopropane derivatives possess a masked ketone group, and serve as important building blocks for the synthesis of the corresponding y-oxo esters (eq 45). ... 

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