Other Syntheses of Six-membered Rings

Thus reaction of an enolate anion, formed either by proton 

A double Michael reaction of a,8-unsaturated ketones with 

but lengthy annulation sequence which controls three 

The power of radical ring closure reactions is demonstrated most elegantly in a synthesis of isoamijiol, in which a whole range of carbon-carbon bond forming reactions are used including the cyclization of the ketone (63).11,6 Additionally, the use of a new substrate in radical cyclizations (64) allows access to both six and five-membered rings in a process which for success requires the halide to be on an sp carbon.1 Furthermore a useful, and 

Polyene Cyclizations. - This too is an area of decreasing activity but some interesting contributions have appeared. For instance the 

Other Syntheses of Six-membered Rings.- Comprehensive details of 

Michael reaction has been used in the total synthesis of atisiran-15-one. 

Multiple carbon-carbon bond forming reactions are of course invaluable and now a Michael-Michael-r ing closure (MIMIRC) process 

B-Keto-esters containing an alkene will undergo a manganese(III) oxidation reaction resulting in ring closure as shown in the reaction of (91). However other examples proceed in poor yield only. a,w-Bis-allylie acetates such as (92) undergo a palla-dium(0)-induced reductive cyclization in the presence of hexa- 

In a further elegant example of the utility of intramolecular radical cyclizations in ring formation, ( )-alliacolide has been synthesized using the cyclization of (93)In a well conceived 

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Other Syntheses of Six-membered Rings. - The use of multi-component, one-pot annulation sequences offers considerable synthetic scope as demonstrated by a new cyclohexanone forming reaction (Scheme 13). 

The groups of Burczyk, Takeda, and others have made thorough studies of cyclic acetals, such as 1,3-dioxolane (five-membered ring) and 1,3-dioxane (six-membered ring) compounds, illustrated in Fig. 13. They are typically synthesized from a long-chain aldehyde by reaction with a diol or a higher polyol. Reaction with a vicinal diol gives the dioxolane [40-42] and 1,3-diols yield dioxanes [43,44]. 

According to the reaction types these syntheses may be classified as cyclocondensations, cycloadditions, or oxidative cyclizations (80PAC1611). To some extent TPs are prepared by other transformations of the five- and/or six-membered ring. 

As indicated in Scheme VII/32, cyclononanone (VII/165) is transformed into hydroperoxide hemiacetal, VII/167, which is isolated as a mixture of stereoisomers. The addition of Fe(II)S04 to a solution of VII/167 in methanol saturated with Cu(OAc)2 gave ( )-recifeiolide (VII/171) in quantitative yield. No isomeric olefins were detected. In the first step of the proposed mechanism, an electron from Fe2+ is transferred to the peroxide to form the oxy radical VII/168. The central C,C-bond is weakened by antiperiplanar overlap with the lone pair on the ether oxygen. Cleavage of this bond leads to the secondary carbon radical VII/169, which yields, by an oxidative coupling with Cu(OAc)2, the alkyl copper intermediate VII/170. If we assume that the alkyl copper intermediate, VII/170, exists (a) as a (Z)-ester, stabilized by n (ether O) —> <7 (C=0) overlap (anomeric effect), and (b) is internally coordinated by the ester to form a pseudo-six-membered ring, then only one of the four -hydrogens is available for a syn-//-elimination. [111]. This reaction principle has been used in other macrolide syntheses, too [112] [113]. 

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