Cyclopropyl ketones protonation

Larger changes in bond lengths, as expected, are observed for more localized carbocations. Most of the structures available are for stabilized systems, such as protonated carbonyl compounds [e.g. the protonated cyclopropyl ketones referred to on page 110 (Childs et al., 1990), and dioxacarbocations (Paulsen and Dammeyer, 1973, 1976 Paulsen and Schuttpelz, 1979 Childs et al., 1986, 1991). It is normal to see one of the atoms of the counterion (in most cases MXJ or MX ) packing in the position expected for addition to the activated C=OH(R)+ system, apparently just within the sum of the van der Waals radii for the neutral centres (Childs et al., 1986). This can happen without significant pyramida-lization, however (Childs et al., 1991), and on both sides of the planar carbon centre it tells us little new about reactivity. 

Another widely used approach is the cyclization of oximes either under acidic, as in the conversion (147 ->148) (71MI22700), or basic conditions (149- 150) (78JOC2020). Cyclopropyl ketones (151) also react with hydroxylamine hydrochloride to give dihydro-1,2-oxazines (153), probably via the protonated oxime (152). If this is so then this reaction represents a rare example of a 6-endo-tet ring closure <80AG(E)199). 

Alkyl cyclopropyl ketones or dicyclopropyl ketones in fluorosulfuric acid/sulfuryl chloride fluoride at about -90 °C undergo O-protonation to a-hydroxycyclopropyl-carbinyl cations (equation 7). These cations are essentially protonated ketones, as the positive charge heavily resides on the oxygen atom16. X-ray structural studies have also been carried out on hydroxycyclopropylcarbinyl cation salts, since they are easily obtained as crystalline materials17. 

The reductive opening of a cyclopropane ring of a conjugated cyclopropyl ketone with lithium in liquid ammonia can be viewed as an overall two electrons reduction which yields the equivalent of a carbanion and an enolate ion (cf. 237). Successive protonations of 237 then gives the reduced ketone. 

It has been found that cyclopropyl ketone exhibits a conformer mixture The preferred component has been identified as the bisected s-c/s conformer At the present time, however, it is not clear whether the second conformer (less stable) corresponds to the bisected s-trans form or anti-gauche form. On the other hand, on the basis of a theoretical analysis (on the semiempirical INDO-level) and a proton NMR investigation for the cis-trans isomeric 2-methylcyclopropyl-l (methyl) ketones 15 and 16 it was suggested that the trans compound 15 exists as an equilibrium of the bisected s-cis and s-trans conformers. The s-c/s and s-trans conformers are separated by a rotational barrier of 5.7 kcal mol ... 

Acceptor ability of a group can be enhanced by interaction with a suitable electrophile (proton, Lewis acid). This is very likely in the Ni(acac)2-catalysed reaction of cyclopropyl ketones with trimethylaluminium and in the synthetically more significant addition of several cuprates to alkyl cyclopropyl ketones. The BFs-activated organometallic reagent attacks the less substituted cyclopropane carbon regioselectively. Yet steric hindrance can be a problem in this reaction (equation 40) . 

Cyclopropyl ketone oximes 35 were converted to 5,6-dihydro-l,2-oxazines 36 on refluxing in ethanol with acid. Alternatively, the original ketones 34 sustained the same transformation on prolonged heating with hydroxylamine hydrochloride in ethanol. A plausible mechanism involves protonation of the nitrogen atom followed by endo-tet ring closure. 

The rearrangement of protonated cyclopropyl ketones to 1,4-diones has been described previously. Now the important prostaglandin precursor (7) has been prepared from the keto-acid (8) through such a rearrangement (Scheme 22). ... 

A project directed towards the synthesis of chrysanthemic acid enantiomers illustrates some of our recent work on cyclopropano-pyranosides. The sequence (Scheme 40) that had worked so well (25) for the preparation of the simple cyclopropyl ketone (169) from the methanol adduct (168) was not adaptable for preparation of the gem-dimethyl analogue (171). The photoaddition of isopropanol to (83) gave an excellent yield of (170), but efforts to convert this into (171) were not encouraging. However, the Wittig cyclopropanation (24) of epoxide (51) gave the ester (172) whose stereochemistry was deduced by two pieces of nmr data (a) the value J12 < 1 Hz (76) (see Scheme 4), and (b) a ten percent Nuclear Overhauser Effect between H-1 and the methyl protons. 

In extensions of some earlier studies, Wada et al. have shown that a useful method of cyclopentane annelation is by rearrangement of protonated cyclopropyl ketones, to y-hydroxy-ketones, viz. (51), followed by oxidation to 1,4-diones and base-catalysed cyclization (Scheme 16). Both oxidation of a-allyl-ketones, using PdCl2-CuCl in DMF under an oxygen atmosphere, and the oxidative cleavage of t-cyclobutanols using Jones reagent provide alternative new approaches to... 

Gassman and Creary have reported that the centra bond of succinic esters can be cleaved with sodium in liquid ammonia. This method gives dimethyl glutarate from dimethyl cis- and trans-cyclopropane-l,2-dicarboxylates. The C-1—C-2 cleavage of a 1,2-diphenylcycIopropane which is part of a more complex, tricyclic compound has been effected by lithium in ammonia. Although it is known that lithium-ammonia reduction of a cyclopropyl ketone cleaves the bond which will allow tlw best overlap with the carbonyl Tt-system, the steric course of protonation at the f(-carbon has not, until recently, been known. Reduction of (301) at — 78 °C gives (302X the product with inversion, and (303),... 

In terms of the bicyclo[3.1. OJhexenyl ions, the structure of the protonated ketone 65 was determined by Childs, Lock and colleagues60. The bond distances associated with the protonated carbonyl group and unsaturated portion of 65 were completely consistent with those expected for a protonated enone (Table 5). However, comparison of the cyclopropyl portion of structure 65 with that of the 2-hydroxyhomotropenylium ion (vide supra) and... 

Cyclopropyl-substituted ketones are suitable substrates for generating distonic radical anions from ketyl radical anions. A series of cycloalkanone substrates with unsaturated side-chains, to trap the primary radical formed after cyclopropylcar-binyl ring opening, has been investigated (Scheme 31) [118, 119]. For the first electron-transfer step triethylamine is used as electron donor. The reaction sequence is terminated by proton or hydrogen transfer from the solvent or the a-amino radical formed after deprotonation of the amine radical cation. 

The gas phase basicity (GB) values in Table 15 for ketones and esters show that cyclopropyl consistently favors protonation relative to isopropyl, although the difference is only 1.3 kcal mol for the esters. Phenyl is slightly more stabilizing than cyclopropyl in each case. In solution the phenyl-substituted compounds in Table 15 are consistently the least basic and cyclopropyl the most basic. The low basicity of the phenyl derivatives in dilute acid has been ascribed to the poor hydrogen bonding to the protonated aryl carbonyP. ... 

The heats of protonation of the ketones 131-135 (Table 17) indicate that the vinyl and cyclopropyl groups both give a nearly 5 kcal mol more favorable heat of reaction, and consideration of ground state energies probably would make the difference even greater... 

Conjugative and substituent properties of the cyclopropyl group TABLE 17. Heats of protonation of ketones... 

Trost and co-workers used this type of rearrangement to generate oxaspiropentane derivatives that were converted to cyclo-butane derivatives. In section 8.8.B.ii, oxaspiropentanes such as 61 were prepared by the reaction of ketones and sulfur stabilized cyclopropyl ylids. Treatment of 61 with aqueous tetrafluoroboric acid (HBF4) gave cation 62, which rearranged to 63. Loss of a proton gave the final product, ketone 64. ... 

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