Baeyer cyclobutanone

Cyclobutanone annulation onto a carbonyl group translates into y-butyrolactone annulation because of the facility of the Baeyer-Villiger reaction (Eq. 68 a)8). Indeed, the reaction proceeds sufficiently rapidly that even basic hydrogen peroxide effects the oxidation whereas, with less reactive carbonyl partners, peracids must be used. 

At this time, we can focus on the creation of the butenolide. Sulfur based methodoly allows simplification to the simple butanolide as in 170. While cyclobutanone spiroannulation of 171 followed by a Baeyer-Villiger reaction would create 170,... 

In Grieco s total synthesis of the antileukemic secoeudesmanolides ivangulin (194)67) and eriolanin (197)68), the Baeyer-Villiger oxidation was again found to be indispensable in the conversion of the cyclobutanones (192) and (195) to the y-lactones (193) and (196)respectively 67,68). 

A systematic study of the Baeyer-Villiger oxidation of cyclobutanones was recently reported by Jeffs71). The cycloalkenes (206) reacted readily with dichloro-ketene to give the gem-dichlorocyclobutanone (205), which were reduced by Zn to the cyclobutanone (204). Baeyer-Villiger oxidation of (204) yielded the y-lactone (207) in fair yields. (Table 11)71). 

The stereoselective [2+2] cycloaddition between ketenes and enolethers can be used as a key step in the construction of y-butyrolactones (Scheme 14) [45], if the resulting cyclobutanones can subsequently undergo ring enlargement by a regioselective Baeyer-Villiger oxidation. 

In the same year, chiral phosphoric acids were found to catalyze the enantioselective Baeyer-ViUiger (BY) oxidation of 3-substituted cyclobutanones 140 with aqueous... 

Scheme 56 Baeyer-Villiger oxidation of 3-substituted cyclobutanones...

SCHEME 171. Titanium-catalyzed asymmetric Baeyer-VilUger oxidation of cyclobutanones... 

Another method for the asymmetric version of the Baeyer-Villiger reaction was presented by Lopp and coworkers in 1996 . By employing overstoichiometric quantities of Ti(OPr-t)4/DET/TBHP (1.5 eq./1.8 eq./1.5 eq.), racemic andprochiral cyclobutanones were converted to enantiomerically enriched lactones with ee values up to 75% and moderate conversions up to 40% (Scheme 171). Bolm and Beckmann used a combination of axially chiral C2-symmetric diols of the BINOL type as ligands in the zirconium-mediated Baeyer-Villiger reaction of cyclobutanone derivatives in the presence of TBHP (or CHP) as oxidant (Scheme 172) . With the in situ formed catalysts 233a-d the regioisomeric lactones were produced with moderate asymmetric inductions (6-84%). The main drawback of this method is the need of stoichiometric amounts of zirconium catalyst. 

TO PALLADIUM-CATALYZED ASYMMETRIC BAEYER-VILUGER OXIDATION OF PROCHKAL CYCLOBUTANONES. 256... 

SYNTHESIS OF 2-(PHOSPHINOPHENYL)PYRINDINE LIGAND AND ITS APPLICATION TO PALLADIUM-CATALYZED ASYMMETRIC BAEYER-VILLIGER OXIDATION OF PROCHIRAL CYCLOBUTANONES... 

Table 7.1 Asymmetric Baeyer-ViUiger oxidation of several cyclobutanones using chiral palladium complex"...

The use of a chiral hydroperoxide as oxidant in the asymmetric Baeyer-Villiger reaction was also described by Aoki and Seebach, who tested the asymmetric induction of their TADOOH hydroperoxide in this kind of reaction98. Besides epoxidation and sulfoxidation, for which they found high enantioselectivities with TADOOH (60), this oxidant is also able to induce high asymmetry in Baeyer-Villiger oxidations of racemic cyclobutanone derivatives in the presence of DBU as a base and LiCl as additive (Scheme 174). The yields and ee values (in parentheses) of ketones and lactones are given in Scheme 174 as... 

The Baeyer-Villiger oxidation of acyl-substituted cyclobutanones 1 is reported to be very slow with ordinary peracids such as 3-chloroperoxybenzoic acid24- 31 37 38 and peracetic acid.24,36 Generally, reaction times of several weeks are needed to obtain acceptable yields of acyloxycy-... 

Linkers that enable the preparation of y-lactones by cleavage of hydroxy esters from insoluble supports are discussed in Section 3.5.2. Resin-bound y-lactones have been prepared by Baeyer-Villiger oxidation of cyclobutanones [39], by intramolecular addition of alkyl radicals to oximes [48], by electrophilic addition of resin-bound sele-nenyl cyanide or bromide to 3,y-unsaturated acids (Figure 9.2 [100]), and by palladium-mediated coupling of resin-bound aryl iodides with allenyl carboxylic acids (Entry 10, Table 5.7 [101]). 

The key steps in the ring expansion of the cyclobutanones (186) and (787) are the Baeyer-Villiger oxidation effected by H202—HOAc. It is noteworthy to point out that the Baeyer-Villiger oxidation is regiospecific and serves to be an excellent method for the preparation of y-lactone from cyclobutanones. 

Incorporation of substituted BINOL ligands improved the enantioselectivity of asymmetric Baeyer-Villiger oxidations of prochiral cyclobutanones with CHP and... 

Alphand V, Mazzini C et al (1998) A new microorganism for highly stereospecific Baeyer-Villiger oxidation of prochiral cyclobutanones. J Mol Catal B Enzym 5 219-221... 

Both the Baeyer-Villiger and the Beckmann rearrangement are used on the cyclobutanones formed in these cycloadditions. Dechlorination of adduct 12 with zinc and rearrangement with a peroxy-acid gives a lactone 25 widely used in prostaglandin synthesis.5 Note that the more substituted carbon migrates and does so with retention of configuration. 

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