Cyclobutanone, diastereoselectivity

For example, an oxaspirohexane <52, readily available by condensing cyclobutanone 61 with dimethylsulfonium methylide, rapidly rearranges (isomerizes) to the cyclopentanone 63 upon exposure to a catalytic amount of lithium bromide55). The high diastereoselectivity of the initial cyclobutanone formation translates into a high diastereoselectivity for cyclopentanone annulation as this example of Eq. 74 demonstrates. 

Using (-)-lOO [46] as a chiral auxiliary tethered to the enolether, one face of the alkene can be specifically blocked by a n-n interaction of the phenyl rest for the [2 r5+2 r ] cycloaddition with a ketene [47], resulting in the highly diastereoselective formation of the cyclobutanone 102 (Scheme 15). The observed regio- and stereoselectivity is in accord with the stereochemical predictions made on the basis of the Woodward-Hoffmann... 

Intermolecular coupling of ketones and alkenes, promoted by SmH, occurs with excellent stereochemical control. In one such reaction, samarium(II) iodide has been used to prepare cyclobutanones and cyclobutanols from chiral, 6-oxohex-2-enoates (equation 137)520. The reaction is performed in THF in the presence of HMPT and occurs in good yield with excellent stereocontrol. If appropriately located carbonyl and alkene moieties are present in a molecule, then Sml2-HMPT can be used to form cyclooctanols by a radical cyclization process in some cases there is a reasonable degree of diastereoselectivity (equation 138)521,522. 

An ab initio study of the 2 + 2-cycloadditions of allene to isocyanic acid and ketene to vinylimine found the reactions to be concerted and mostly asynchronous.28,29 The diastereoselective 2 + 2-cycloaddition of dichloroketene with a chiral enol ether (26) produced the cyclobutanone (27), which leads to a key intermediate (28) in (g) the total synthesis of the natural alkaloid (-)-Swainsonine (29) (Scheme 8).30 The... 

Similar to the thermal reaction of ketenes with alkenes, the photolysis of alkoxycarbenes 18 in the presence of (electron-rich) olefins 19 leads to cyclobutanones (Scheme 6) [9]. In these reactions the sterically more strained [2 + 2] cycloadducts of type rac-17 are generally formed with good regio- and diastereoselectivity. Starting from complexes of type 21, the intramolecular version of this reaction affords bicyclic products of type rac-20 (Scheme 7) [9]. 

The efficiency of this method was demonstrated in a total synthesis of the antibiotic (-r)-tetrahy-drocerulenin 28 (Scheme 8) and (-h)-cerulenin [11]. Irradiation of complex 22 in the presence of the chiral iV-vinyl-oxazolidinone 24, which is easily prepared from the amino carbene complex 23 [12], leads to the cyclobutanone 25 with high diastereoselectivity. Regioselective Baeyer-Villiger oxidation followed by base-induced elimination of the chiral carbamate yields the butenolide 26 in high enantiomeric purity. This is finally converted, using Nozoe s protocol [13], to the target molecule 28 by diastereo-selective epoxidation (- 27) and subsequent aminolysis. 

Irradiation of alkoxycarbene complexes in the presence of aUcenes and carbon monoxide produces cyclobutanones. A variety of inter- and intramolecular [2 + 2]cycloadditions have been reported. The regioselectivity is comparable with those obtained in reactions of ketenes generated from carboxylic acid derivatives. Cyclobutanones can be obtained with a high degree of diastereoselectivity upon reaction of alkoxy carbenes with chiral A-vinyloxazolidinones. For example, photolysis of (19) in the presence of (20) gives cyclobutanone (21) (Scheme 31). In addition to aUcoxycarbenes, carbenes having a thioether or pyrrole substituent can also be employed. Related intramolecular cycloadditions of y,5-unsaturated chromimn carbenes afford bicyclo[2.1. IJhexanones (Scheme 32). 

Induced diastereoselectivity is also observed with chiral ketenes. Menthyloxymethylketene adds to (Z)-l-benzvloxy-l-hexene to give 50% of a 5 1 mixture of cyclobutanones. The structure of the major diastereomer was established by conversion to (—)-blastmycinone18. 

The first reported examples of Lewis acid-catalyzed ketene-alkene [2+2] cycloadditions provide efficient and diastereoselective routes to cyclobutanones (Scheme 7.53). In this procedure, the alkene is added to a ketene solution generated by dehydrochlorination but is not reactive until the mixture is added to the catalyst solution. Catalyzed reactions with conjugated alkenes such as cyclopentadiene favor the opposite diastereoselectivity to that of the corresponding thermal reactions. 

The racemic mixture of cyclobutanones is converted into bisulphite adducts (note that diastereoselective attack of the bisulphite anion takes place exclusively anti to the two adjacent substituents). Fractional crystallisation of the salt formed with enantiomerically pure (5)-l-phenylethylamine allows separation of the (25,4/ )-diastereomer (1), which, after decomposition of the bisulphite adduct, undergoes a Favorskii-type ring contraction and elimination of HCl to give enantiomerically pure (2). The undesired (2R, 45) diastereomer can be converted back to the racemic mixture for recycling, rendering the process highly efficient. "... 

The 2 -I- 2-cycloaddition reactions of chiral Al-alkynylated sulfoximines with ketenes afforded sulfoximine-functionalized cyclobutenes in high yields. The first examples of Lewis-acid-promoted ketene-alkene 2-i-2-cycloadditions yielded cyclobutanone cycloadducts with good yields and diastereoselectivity. " ... 

Ketiminium salts have been shown to participate readily in [2-r 2]-cyclo-additions with olefins [35]. Ghosez reported a classic in this area, involving the use of prolinol-derived ketiminium species (Scheme 18.28) [122]. Treatment of a-chloroenamine 172 with ZnCl2 facilitated chloride abstraction under mild conditions to yield an intermediate ketiminium salt 173. The reactive cumulene participated in a diastereoselective cycloaddition with cyclo-pentene to afford the chiral ketone 174 (> 97 % ee), after hydrolytic removal of the auxiliary. These diastereoselective [2 2]-cycloadditions of Ghosez provide a rare example of a chiral auxiliaiy-based approach to chiral cyclobutanones. 

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