Acetals cyclopropanones

Ethenylcyclopropyl tosylates 131 and 2-cyclopropylideneethyl acetates 133, readily available from the cyclopropanone hemiacetals 130, undergo the re-gioselective Pd(0)-catalyzed nucleophilic substitution via the unsymmetrical 1,1-dimethylene-jr-allyl complexes. For example, reduction with sodium formate affords a useful route from 131 to the strained methylenecyclopropane derivatives 132. The regioselective attack of the hydride is caused by the sterically... 

Product distribution in the reaction of 4 with furan depends on the reaction conditions as well as on the oxy group of the acetal substrates 4a-c. The diverse products formed in the reaction of 4a-c with furan are rationalized by the reaction pathways illustrated in Scheme 13. All products arise from nucleophilic addition of furan to alkylideneallyl cation intermediate 5M (5S), which is generated by acid-mediated ring opening of cyclopropanone acetals 4a-c (Scheme 5). The [4 + 3] cycloadduct 23 is simply formed via 27, and the furanyl... 

However, the hemiaminal 17 is unstable as a free base and readily undergoes exchange reactions. Since the hydroxy moiety of 17 is more easily displaced than the amine moiety, a highly reactive cyclopropyliminium salt 18 is formed, which then reacts with weak nucleophiles such as ethanol, to give e. g., 19. Otherwise in water solution 17 can also probably eliminate ammonia to form the highly reactive cyclopropanone 20, which is in equilibrium with its hydrate 21 and hemi-acetal 22, Eq. (8) [20]. It has been reported that hydrate 21 is also a potent inhibitor of ALDH [20,21]. 

Bis(oxazoline) ligands have been shown to be useful in the many carbon-carbon bond-forming reactions previously listed. They have also been used in a myriad of other carbon-carbon bond-forming reactions. For example, Nakamura and coworkers used bis(oxazoline) ligands ent-2, ent-22, and ent-39 in ligand-induced enantioselective allylzincation. This reaction consisted of the transformation of the cyclopropenone acetal 198 into allylic cyclopropanone acetal 199 in yields ranging from 73 to 90% with selectivities from >98 2 for the isomer shown to 1 99 (Fig. 9.57). 

Alternatively, the reaction of cyclopropylethynylmagnesium bromide with cyclo-propanone hemiacetal gives l-(cyclopropylethynyl)cyclopropanol (equation 152)232. The reaction of cyclopropanone acetal with other alkynyl Grignard reagents serves as a general route to alkynylcyclopropanols. Similarly, alkynyllithium derivatives of vitamin D were coupled with cyclopropane carbonyl isoxazolidine to give the corresponding alkynyl-cyclopropyl ketones (equation 153). 

When getw-dibromocyclopropanes are heated with alcoholic potash, cyclopropanone acetals and propargylic ethers are obtained.42 The mechanism was discussed. 

Until quite recently, cyclopropanones were known only as transient intermediates, or in the form of derivatives such as the hydrate or hemi-acetal. x> During the past decade, however, through the work of the groups at Columbia 2> and Amsterdam 3> among others, methods have been developed for preparing a number of representatives of this class. Table 1 lists various cyclopropanones which have been isolated as well as several, more elusive examples which have been characterized in solution. 

As shown in Table 2, the application of this method to the synthesis of aryl-substituted cyclopropanones 16> and cyclopropanone acetals 17>18> has been moderately successful, although products other than the expected ketones may be obtained. For example, the oxadiazoline 4 and not tetraphenylcyclopropanone is formed when diphenylketene is allowed to react with diphenyldiazomethane.19>... 

The Simmons-Smith reagent also adds to ketene acetals forming cyclopropanone acetals, as shown in the formation of 1,1-dimethoxy-2,2-dimethylcyclopropane (8) from l,l-dimethoxy-2,2-dimethylethyl-ene.17) Similarly, with methylene iodide, ketene o-xylylene acetal (9) affords the corresponding cyclopropanone derivative (JO) (70%).24)... 

Cyclopropanone acetals may also be prepared by the addition of other one-carbon species to ketene acetals as shown in Table 3. Thus, McElvain and Weyna have synthesized several cyclopropanone deriv-... 

Schollkopf and co-workers have synthesized a number of cyclopropanone acetals by the addition of various sulfur- and oxygen-containing carbenes to ketene diethylacetals (Table 3).26>27> Similarly, cyclopropanone dithioacetals may be prepared by the addition of the Ws-thiomethyl and Ws-thiobenzylcarbenes 12a, b to olefins.29) However, cyclopropanone acetal formation by this method requires double bonds with considerable electron enrichment and the yields are generally low. With unsubstituted olefins such as cyclohexene, the carbenes 12 a, b tend to form dimeric and trimeric products such as 13 and 14, instead of the double bond addition products. 

Table 3. Cyclopropanone acetals and thioacetals from carbene additions...

The cyclopropyl enone 31 was photoisomerized to the cyclopropanone 32 at liquid nitrogen temperatures.34) The unstable 32 was characterized on the basis of ir spectra and thermal and photochemical reactions (see Section 4.1.5). When 31 was irradiated at room temperature in 45% acetic acid, the phenol 33 was produced, most probably through 32 and the spiro dienone intermediate 34 (Scheme 5).35>... 

Cyclopropanone hemiacetals and hydrate react with ketene to form acetoxy derivatives, e.g. 86 and 87, respectively. 5 15>80) As shown in Scheme 14, the diacetoxy compound 87 may also be obtained from the reaction of cyclopropanone with acetic acid and excess ketene. 83>... 

Presumably, 1-acetoxycyclopropanol (88) is the intermediate in this reaction as well as that between the hydrate and ketene. 80> Although 88 has not been isolated in the above cases, it may be prepared from acetic acid and cyclopropanone and reacts with ketene to give 87. 5>15>... 

Cyclopropanone acetals require far more vigorous conditions (concentrated acid and heating) for ring cleavage compared to hemiacetals. As shown in Scheme 28, the reaction may proceed in two directions, one involving O-protonation (a) and the other C-protonation (b). In the case of 1,1-diethoxycyclopropane where both paths are competitive, refluxing hydrochloric acid yields both chloroacetone and ethyl propionate (Table 17).25)... 

Table 17. Ring opening reactions of cyclopropanone acetals under acidic conditions... 

The cyclopropanone ring is susceptible to attack by electrophilic reagents other than acids, e.g. bromine, phenol, acid chlorides. Most of these reactions have been observed in cyclopropanone acetals and all proceed by attack at C2 or Cg in a manner analogous to path b, Scheme 28. As shown in Table 18, esters are usually obtained but, under special bro-mination conditions, 1,1-dialkoxycarbonium halides are formed.109) These salts lose ROBr upon warming to — 30 °C to give the expected esters. 

Tellurium tetrachloride and 1-isopropoxy-l-trimethylsiloxycydopropane, an acetal of cyclopropanone, reacted in dichloromethane solution at 20° to give bis[2-isopropoxy-curboriylethyH tellurium dichloride2. 

The procedures described herein illustrate the preparation of a substituted cyclopropenone acetal and an alkylidene cyclopropanone acetal.The latter compound has been used to generate a dipolar trimethylenemethane (TMM) species that undergoes [3+2] cycloaddition with electron-deficient 2p-electron C=C and C=X compounds. ... 

The substitution reactions of cyclopropanone acetals and aminals have been reviewed and are discussed in Chapters 22 and 23. These compounds readily undergo the substitution with various nucleophiles, such as Grignard reagents (equation... 

---