Systems Ireland- Claisen rearrangement

Ireland-Claisen rearrangement as an alternative approach to the syn isomer with a high degree of diastereoselectivity was also examined. This reaction might be similar to the system of ester-enolate [2,3]-Wittig shift in the case of OR (R=protective group). 

Alkenyl-2-azetidinone systems could be converted to bicyclic (3-lactam carboxylic esters and hence carboxylic acids (Fig. 5) via tandem Ireland-Claisen rearrangement and subsequent alkene metathesis [250],... 

Por a competitive retro-Diels-Alder-Diels-Alder sequence in the attempted Ireland-Claisen rearrangement of a perhydroindane ring system, see S. D. Burke, D. M. Armistead and K. Shankaran, Tetrahedron Lett., 1986, 27, 6295. 

The Claisen rearrangement of bis-allyl vinyl ethers and related systems has been studied by several groups [98]. Modest to high levels of regioselectivity were obtained in the parent Claisen as well as Johnson, Eschenmoser and Ireland variants of the reaction. Parker and Farmar applied the ester enolate variant of the Ireland-Claisen rearrangement of a bis-aUylic ester to the synthesis of biflora-4,10(19),15-triene, using the rearrangement to install the 1,3-diene component for a subsequent intramolecular Diels-Alder reaction [99]. 

Curran proposed a vinylogous anomeric effect concept to explain the observed rate difference of the Ireland-Claisen rearrangements of dihydropyran 152 and cyclohexene system 155. Oxygen attached to Ce is proposed to stabilise the polar Ireland-Claisen intermediates 160-161 which contribute to a faster rate of reaction. ... 

R. E. Ireland and J. P. Vevert, A chiral total synthesis of (—) and (+) nonactic acids from carbohydrate precursors and the definition of the transition for the enolate Claisen rearrangement in heterocyclic systems, J. Org. Chem. 45 4259 (1980). 

Previously, Ireland-Claisen ester-enolate rearrangement of the corresponding a-propionyloxy-allylsilane led to model system 5.44 Therefore, elaboration to 4 via rearrangement of 15 was pursued. To complete our retrosynthetic analysis, a plausible route to 15 was devised, involving straightforward homologation of 2P,3a-disubstituted cyclohexanone 17 to cyclohexene-carboxaldehyde 16, which in turn undergoes silylanion addition and subsequent acylation (Eq. 8). 

Although a chairlike transition state is favored for the Claisen rearrangement reactions of acyclic substrates, this is not always the case with cyclic systems. For example, Bartlett and Ireland independently studied the rearrangement reactions of cyclohexenyl silylketeneacetals and found that there was competition between the chairlike and boatlike transition states11 (Scheme l.VII). Clearly, the -isomer IE gives 8a via a chairlike transition state, whereas the Z-isomer 7Z affords the same product (8a) via a boatlike transition state. 

Taking advantage of the likewise mild conditions of the Ireland version of the Claisen rearrangement, easily accessible ester or lactone bonds may be transformed via their enolates into C—C bonds. In the case of cyclic systems, the ring size may be varied by the position of the double bonds. Recently Funk et al. made use of this often applied principle for the synthesis of tricycle 76 (shown in Scheme 18) (76). 

In cyclic systems, however, conformational constraints can override the inherent preference for chairlike transition states in Cope as well as Claisen rearrangements and lead to a partial involvement if not a dominance of boat-like TS structures. In the Ireland rearrangement of lactones of type (247), for example, chair-like transition state (249) is accessible only when the diaxial bridging methylene chain becomes sufficient in length (n = 7, Scheme 44). The preference of boat-like transition state (250) over (251) is due to a serious A - -type interaction between the endocyclic oxygen atom and pseudoaxial substituent R in (251). 

The Ireland variant of the Claisen rearrangement relies on the generation of the vinyl moiety of the double unsaturated system by enolization of an ester. The principle of this technique is given in Scheme 11.42 and it allows the transformation of allylic alcohol 177 into 180 via ester 178 and the ketene acetal 179. Application of this chemistry to the construction of the chiral quaternary carbon atom of the zaragozic acid core is shown in Scheme 11.47 [142]. Additional examples of this rearrangement are found in Section 11.5.2.2. 

The potential of the ester enolate Claisen rearrangement for the stereocontrolled synthesis of highly functionalized, complex systems has been demonstrated in numerous applications in natural product synthesis. Utilizing the 1,3-chirality transfer Ireland has synthesized oxygen heterocycles with chiral side chains, such as are found as units in polyether antibiotics and macrolides, starting from enantiomerically pure furanoid or pyranoid glycal systems of type (41), which are easily accessible from carbohydrates (Scheme 65). ... 

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