Cyclopropanone ketals

Figure 4.8 The ketene acetale 187 is the expected product of [3+2]-cycloaddition of methylene cyclopropanone ketal to Qo-...

Addition of cinnamyl(mesityl)zinc to the C2 symmetrical cyclopropenone ketal 133 led to excellent diastereoselectivities with respect to the newly formed carbon—carbon bond (de = 97%) and induction from the chiral ketal (de = 91%). Deuteriolysis afforded the cyclopropanone ketal 134 in which three stereocenters have been generated99,10°. A product-like transition state model was proposed, in which the cyclopropene underwent considerable rehybridization and the zinc became preferentially attached to the less hindered equatorial olefinic carbon from the face opposite to the axial ketal methyl group (equation 65). 

Allylzincation of the monosubstituted cyclopropenone ketal 137 with the chiral reagent 138 proceeded regioselectively so as to generate the less substituted secondary cyclo-propylzinc species 139. After hydrolysis, the resulting cyclopropanone ketal was obtained with high enantiomeric excess ( = 99%). The reaction was very slow at 20 °C but was considerably accelerated under high pressure (1 GPa) (equation 67)102. 

Besides the activation of the olefinic partner by a metal, the unfavorable thermodynamics associated with the addition of an enolate to a carbon—carbon multiple bond could be overwhelmed by using a strained alkene such as a cyclopropene derivative286. Indeed, Nakamura and workers demonstrated that the butylzinc enolate derived from A-methyl-5-valerolactam (447) smoothly reacted with the cyclopropenone ketal 78 and subsequent deuterolysis led to the -substituted cyclopropanone ketal 448, indicating that the carbometallation involved a syn addition process. Moreover, a high level of diastereoselectivity at the newly formed carbon—carbon bond was observed (de = 97%) (equation 191). The butylzinc enolates derived from other amides, lactams, esters and hydrazones also add successfully to the strained cyclopropenone ketal 78. Moreover, the cyclopropylzincs generated are stable and no rearrangements to the more stable zinc enolates occur after the addition. 

The reaction with optically active hydrazones provided an access to optically active ketones. The butylzinc aza-enolate generated from the hydrazone 449 (derived from 4-heptanone and (,S )-1 -amino-2-(methoxymethyl)pyrrolidine (SAMP)) reacted with the cyclopropenone ketal 78 and led to 450 after hydrolysis. The reaction proceeded with 100% of 1,2-diastereoselectivity at the newly formed carbon—carbon bond (mutual diastereo-selection) and 78% of substrate-induced diastereoselectivity (with respect to the chiral induction from the SAMP hydrazone). The latter level of diastereoselection was improved to 87% by the use of the ZnCl enolate derived from 449, at the expense of a slight decrease in yield. Finally, the resulting cyclopropanone ketal 450 could be transformed to the polyfunctional open-chain dicarbonyl compound 451 by removal of the hydrazone moiety and oxymercuration of the three-membered ring (equation 192). 

Cyclopropanecaiboxylic acid, 56, 70 Cyclopropanes, em-dihalo, 56, 32 Cyclopropanone ketals, 58, 40 Cyclopropenes, 58, 40 CYCLOPROPENONE, 57, 41 CYCLOUNDECANONE, 56, 107 Cycloundecanone, 2-hydroxy-, 56, 110 Cycloundecene, 1-caiboxy-, 56, 111 Cycloundecene, 1-methoxy-, 56, 111 1-Cycloundecene-l-carboxylic acid, methyl ester, 56, 108... 

Dimethoxycyclopropene has been converted into a number of cyclopropanone ketals as shown in Scheme 12.61) Alternatively, the ketal 76... 

Allenes and cyclopropanone ketals. Magnesium in THF (or zinc in HMPT) reacts with a,a -dibromo ketals (1) to give allenes (2) and cyclopropanone ketals (3). If zinc IS used in place of magnesium, HMPT is necessary as solvent. 

Recently it has been shown that cyclopropanone ketals and hemiketals can be prepared conveniently by cyclopropanation of ketene alkylsilyl ketals or ketene disilyl ketals with diethylzinc-methylene iodide in ether ... 

More vigorous conditions are required for ring cleavage of cyclopropanone ketals (concentrated acid and heat). As shown in Scheme 18, the reaction may take two pathways (a) 0-protonation, and (b) C-protonation. In the case of 1,1-diethoxycyclopropane where both paths are competitive, refluxing hydrochloric acid yields both chloroacetone and ethyl propionate (Table 10) . 

TABLE 10. Ring-opening reactions of cyclopropanone ketals under acidic conditions ... 

Cyclopropanone ketals have been synthesized by several cyclization processes. Eliminative cyclization of appropriately functionalized propanes (72) is a particularly effective and general method (equation 37). Many anion stabilizing groups X and Y have been successfully employed in combination with a number of different leaving groups, Z. 

TABLE 13. Cyclopropanone ketals by the diazoalkane-ketene ketal reaction ... 

Ketene ketal Conditions Cyclopropanone ketal Yield (%) Ref. 

TABLE 15. Cyclopropanone ketals from carbene additions... 

When certain jS-keto-dithioesters (87) are treated with Grignard reagents, thiophilic addition occurs and 2-hydroxycyclopropanone dithioketals (88) are produced (Scheme 35) Only one isomer is obtained and a concerted cis-homo-l,4-addition has been proposed to account for the stereospecificity observed. Along somewhat similar lines, Giusti and coworkers have synthesized several cyclopropanone ketals by treating l,3-dibromo-2-propanone ketals with active metals (Table 20). Allenes are a byproduct in this reaction. Dihaloketals may also be cyclized electrolytically (Table 21). ... 

TABLE 21. Cyclopropanone ketals from electrolytical reduction of dihaloketals ... 

Scheme 39) The 2-phenylsulfonyl cyclopropanone ketals could be converted to orthoesters (101) on prolonged treatment with alkoxides. 

Tishchenko and coworkers obtained dihydrofuran derivatives when 2-benzoyl-1,1-dichlorocyclopropane (102) was treated with alkoxides (Scheme 40) . Product (107) is highly reminiscent of butenolide (70) obtained by the addition of chloromethoxycarbene to acrolein as discussed earlier (Scheme 29) and may result from ring-opening of cyclopropanone ketal (104). Perhaps a more likely mechanism involves addition of alkoxide to intermediate 103 followed by cyclization 106 - 107. When treated with thiophenoxide, 102 gave cyclopropanone dithioketal (108). A similar result has been obtained by Ban well (Scheme 41) . Treatment of 109 with thiophenoxide gave dithioketal 110 in 98 % yield. In contrast to the results of Tishchenko, however, keto ester products (112) were obtained from 2,2-dichloro-l-acylcyclopropanes (111) and alkoxides (Scheme 42) ... 

The tetraphenyldiene 125 (Scheme 48) undergoes a photochemical rearrangement yielding cyclopropanone ketal (126) and tetraphenylbutadiene " ". ... 

Cyclopropanone ketals undergo a unique [2s + 2a] cycloaddition reaction with tetracyanoethylene (TCNE) ". In the case of cis- and trans-dimethyl 0,S ketals 151... 

Cyclopropanes, 101, 267 Cyclopropanone ketals, 315-316 Cyclopropene, 113 Cyclopropenone, 519 Cyclopropenones, 27, 399 Cyclopropylacetylene, 401 Cyclopropyl azides, 323 Cyclopropylcarbinyl compounds, 53 Cyclopropyldiphenylsulfonium fluoroborate, 211,213-214... 

The yield and the dr (21A/21B) were determined for the cyclopropanone ketals obtained after aqueous workup of the reaction mixture. 

There have been a number of reports aimed at the synthesis of 1-aminocyclop-ropylphosphonates and the corresponding acids. A new, more efficient route to 1-aminocyclopropanephosphonic acid (266) involves a one-pot reaction of cyclopropanone ketal (265) with a benzylamine in acetic acid/ethanol, followed by the addition of triethyl phosphite. Finally deprotection gives the free amino acid (Scheme 44). The reaction is suggested to take place via an imminium... 

Heterosubstituted cydopropanes can be synthesized from appropriate olefins and car-benes. Since cydopropane resembles olefins in its reactivity and is thus an electron-rich carbo-cycle (p. 76ff.), it forms complexes with Lewis adds, e.g. TiCU, and is thereby destabilized. This effect is even more pronounced in cyclopropanone 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 a1-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 / ,y-unsaturated aldehydes (E.J. Corey, 1975B). 

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