Acyloin cyclization

Azacyclanones,2 The usual syntheses of medium-sized azacyclanones involve Dicckmann or acyloin cyclization conducted under high dilution. An interesting new approach involves hydroboration-cyanidation (4, 446-447 5, 606-607) of a diunsaturated carbamate such as 1. llydroboration of I with thexylboranc followed by cyanidation under standard conditions gives the cyclic ketone 2 in moderate yield in one step. The product can be rcductivcly cyclizcd to the indoliz.idinc alkaloid 5-coniceine (3). 

From a synthetic point of view, the titanium-induced mframolecular cyclization of dicarbonyl compounds is especially attractive in that carbocyclic rings of all sizes may be prepared in good yields, competitive with those obtained using the Dieckmann and acyloin cyclization methods. The synthesis of medium- and large-ring cycloalkenes by the McMurry reaction requires high-dilution conditions (< 0.0 IM) to repress intermol-ecular polymerization. ... 

Cyclobutane-l,2-dione has been isolated from the bromination of 1,2-bis(trimethyl-siloxy)cyclobutene, prepared by sodium induced acyloin cyclization of butanedioate in the presence of chlorotrimethylsilane . The acyloin cyclization of 1,4-, 1,5- and 1,6-diesters to give four-, five- and six-membered rings and the cyclization of )9-chloro esters to three-membered rings in the presence of chlorotrimethylsilane, which usually requires highly dispersed sodium, has been recently simplified by the use of sonochemical activation. The ring contraction of cyclobutane-1,2-diones to 1-hydroxyeyclopropanecarboxylic acid (7) and derivatives may be catalyzed by aqueous acid or base, by methoxide anion, amines or hydrazines and even takes place, though more slowly, in pure water or ethanol. ... 

Effectively, addition of bromine (1 equivalent) to 3-methyl-l,2-bis(trimethylsiloxy)cy-clobutene, prepared by sodium induced acyloin cyclization of methyl 2-methylbutanoate in the presence of chlorotrimethylsilane, followed by treatment with sodium hydroxide and acidification, gave cfs-l-hydroxy-2-methylcyclopropanecarboxylic acid (9) quantitatively (dia-stereoselectivity > 96%). ... 

The bicyclic a-hydroxy acid 10a was obtained from the ring contraction of the 7,8-bis(trimethyl-siloxy)bicyclo[4.2.0]oct-3,7-diene (product of an acyloin cyclization) either by selective bro-mination at — 40 °C and subsequent hydrolysis or by simple autoxidation under an air stream. On further bromination at 20 °C and subsequent solvolysis in aqueous sodium hydroxide the hydroxycyclopropanecarboxylic acid 10a was transformed into 4-bromo-6-oxatri-cyclo[3.2.1.0 ]octane-7-carboxylic acid (11) by intramolecular cyclization, resulting from the addition of the c <7o-hydroxy group to the cyclohexene double bond. Formation of the product resulting from the addition of the carboxy group was not observed. ... 

Therefore, it must be emphasized that the configuration of the stereocenter was not affected during the sodium induced acyloin cyclization of the enolizable dimethyl (7 )-2-methyl-butanedioate as well as during the subsequent base induced C4 - Cj ring contraction, involving however, a (/ )-3-methylcyclobutane-l,2-dione as an intermediate. 

The value of this cyclization is that yields are satisfactory for all ring sizes, unlike the Thorpe-Ziegler cyclization or the acyloin cyclization, in-which yields are low in the formation of 7-11 membered rings. 

Leonard prepared the nine-membered hydroxyketone (69) in good yield by acyloin cyclization of the aminodiester (174), utilizing high-speed stirring and high dilution (Equation (14)) <54JA5708>. 

Fig. 13 (a) Acyloin cyclization, an example of macroeyelization in an heterogeneous medium (b) scheme for cyclization on a polymer support (c) and synthesis of a cyelopeptide on a polymer support. 

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