Cyclopropanone acetal

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... 

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. 

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...

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. 

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... 

Carbonyl-protected acetals, acylals and aminals were used " in their reductive cyclization to form spiro derivatives of cyclopropanone. Good yields of the three-membered spiro compounds were obtained from the acetals while poor yields were obtained by using the acylals and aminals (Table 3). For example, however, the resulting cyclopropanone acetals... 

Homologiauion. The rea nt catalyzes the reaction of ketene acetals with diazomethane to give cyclopropanone acetals ... 

A similar cyclization to give cyclopropanone acetals 33 was accomplished with magnesium in tetrahydrofuran or zinc in hexamethylphosphoric triamide. However, considerable amounts of allenes were also isolated as byproducts. Acetals derived from linear 1,3-dibromo ketones gave a mixture of spiroacetals and allenes, while acetals derived from cyclic ketones, e.g. 2,6-dibromocyclohexan-l-one, afforded cyclopropanone acetals exclusively. In general, the more substituted the substrate, the greater the yield of cyclpropanone acetals. ... 

For example, irradiation of 3,5-di-fert-butyl-6,6-dimethoxycyclohexa-2,4-dienone (5) furnished l,4-di- ert-butyl-6,6-dimethoxybicyclo[3.1.0]hex-3-en-2-one (6). When a small amount of p-toluenesulfonic acid was added to the irradiated solutions, the cyclopropanone acetal 6 underwent protonation followed by ring opening of the three-membered ring and hydrolysis to give methyl 2,5-di-terr-butyl-4-oxocyclopent-2-enecarboxylate (7) in 72% overall yield. ... 

The addition of carbenes or carbenoids to 1,1-dioxygenated alkenes provides access to cyclopropanone acetals or related compounds. ... 

Cyclopropanone acetals can also be obtained by addition of dialkoxycarbenes to C — C double bonds (see Section 5.2.3.5.). Dialkoxycarbenes can be generated by thermolysis of chlorinated 7,7-dialkoxybicyclo[2.2.1]heptadiene derivatives by photolysis or thermolysis... 

The latter cyclization is also obtained with acetals of a,a-dibromo ketones upon treatment with magnesium in tetrahydrofuran or zinc in hexamethyl phosphoramide. However, a drawback to this method is the formation of considerable amounts of allenes. With magnesium as reagent cyclopropanone acetals were formed in 37-93% (and allenes in 0-47%), while with zinc the yields of cyclopropanone acetals are much lower (20-28%) than those of the allenes (20-70%). ... 

A reactive source of cyclopropane derivatives capable of furnishing cyclopropanone acetals is 1-chloro-l-methoxycyclopropane (33), which reacts with methanol in the presence of silver salts to give cyclopropanone dimethyl acetal (34) without rupture of the three-membered ring. It was subsequently shown that methanolysis, which occurs via an S l mechanism, does not require silver salts and occurs in quantitative yield with or without added base. ... 

Much more reactive are cyclopropanone acetals 5 (X = O) and l-methoxy-2-phenylcyclo-propanes 5 (R = Me R = Ph XR" = H). Thus, methyl substituents at C2 (or C3) decrease, and a phenyl substituent increases the reaetion rate. Several facts are in agreement with a concerted [ 2, +, 2a] mode the reaction of cyclopropanone diethyl acetal proceeds ten times more rapidly in the less polar dichloromethane than in aeetonitrile, the molar volume of activation is large and negative, and l-methoxy-2,3-c -dimethyl-l-(methylsulfanyl)cyclopropane (5, R = R = R = Me XR = SMe) reacts with TCNE with inversion at C2 (or C3) to give the fra/15-dimethylcyclopentane derivative 6. 

Cyclopropanone acetals were oxidized by 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) or tetrachlorobenzoquinone in refluxing acetonitrile to the corresponding radical cations which rearranged to o , -unsaturated esters in moderate yields. ... 

Cyclopropanone acetals with a quaternary carbon atom in chiral form can be established by addition of bisoxazoline-ligated allylzinc reagents to the cyclopropenes.The t-BuLi/(-)-sparteine combination favors Br-Li exchange and also promotes enantioselection in the intramolecular addition of aryllithium to an o-alkenyl side chain (e.g., indoline synthe-j.ijj) I28.I29 Moderate asymmetric induction is shown in the hydroarylation of norbomene in the presence of 63. 

An unusual outcome of addition of dichlorocarbene to olefins has been the direct synthesis of cyclopropanone acetals. When dichlorocarbene is generated from ethyl trichloroacetate by sodium alkoxide in a heptane-alcohol medium, carbene addition and solvolysis apparently proceed to a cyclopropanone acetal subsequent acid hydrolysis leads to the corresponding cyclopropanone. This same report claims the synthesis of the dichlorovinylcyclopropanone (68) without loss of the original chloro-substituents. 

From Diazo-compounds. The Wolff rearrangement of a-diazo-ketones has been reviewed and a discussion of the Bamford-Stevens reaction and its associated mechanisms has appeared. The details of a cryochemical synthesis of cyclo-propanone from keten and diazomethane have been described, as have syntheses of cyclopropanone and cyclopropanone acetal. The photolysis of 1-diazobutane, resulting in methylcyclopropane, has been subjected to physico-chemical study. 

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