Rearrangement Ireland

CLAISEN - IRELAND Rearrangment Rearrangement ol allyl phenyl ethers to o (or p-)allylphenols or of allyl vinyl ethers to y.S-unsaturated aldehydes or ketones (Claisen) Rearrangement ol allyl esters as enolale anions to y.S-unsaturated acids (Ireland)... 

Claisen rearrangement of glycolates. Two laboratories 2 have reported that allylic glycolate esters undergo Claisen-Ireland rearrangement (6, 276-277) with useful diastereoselectivity. This rearrangement was used in a synthesis of 1, the aggregation pheromone of the European elm bark beetle.1... 

A Claisen-Ireland rearrangement has been applied to 1-exo-methylene pyranoses bearing enolizable ester functionalities at C-2 (Scheme 12a).65... 

Claisen-Ireland rearrangement of 239 followed by DIBALH reduction gives a mixture of syn and anti isomers 240 (equation 194)34-347. In a similar manner, orthoester Claisen rearrangements of 241 give stereoselectively the corresponding chiral allylsilanes 242 (equation 195)348. 

Ireland-Claisen rearrangements obviously occur under much milder conditions than the classical Claisen rearrangements of Figures 14.46 and 14.47. Among other things, this is due to product development control. The rearranged product of a Claisen-Ireland rearrangement is an a-allylated silyl ester, and its C=0 bond is stabilized by ester resonance (=14 kcal/mol... 

In this chapter we will be dealing primarily with [1,2]-rearrangements. In addition, the most important [3,3]-rearrangements, namely, the Claisen and the Claisen-Ireland rearrangements, will be discussed. 

Fig. 11.43. Claisen-Ireland rearrangement of two O-allyl-O-silyl ketene acetals. 7ran.v-sclective synthesis of disubstituted and E-selective synthesis of trisubstituted alkenes.

The product of a Claisen-Ireland rearrangement essentially is a silyl ester. However, silyl esters generally are so sensitive toward hydrolysis that one usually does not attempt to isolate them. Instead, the silyl esters are hydrolyzed completely during workup. Thus, Claisen-Ireland rearrangements de facto afford carboxylic acids and, more specifically, they afford y,S-unsaturated carboxylic acids. 

Claisen-Ireland rearrangements are extraordinarily interesting from a synthetic point of view for several reasons. First, the Claisen-Ireland rearrangement is an important C=C bond-forming reaction. Second, Claisen-Ireland rearrangements afford y,8-unsaturated carboxylic acids, which are valuable bifunctional compounds. Both of the functional groups of these acids can then be manipulated in a variety of ways. 

Claisen-Ireland rearrangements frequently are used for the synthesis of alkenes.This works particularly well if the allyl ester is derived from a secondary allyl alcohol. In this case a stereogenic double bond is formed in the rearrangement. The examples in Figure 11.43 show that the alkene is mostly fnms-configured if this C=C bond is 1,2-disubstituted and almost completely -configured if it is trisubstituted. 

Structure B corresponds to the most stable transition state of the Claisen-Ireland rearrangement of Figure 11.44. In this transition state, the substituent at the allyllic stereocenter is in a quasi-equatorial orientation with respect to the chair-shaped skeleton. This is the same preferred geometry as in the case of the most stable transition state B of the Claisen rearrangement of Figure 11.43. The reason for this preference is as before that is, an allylic substituent that is oriented in this way experiences the smallest possible interaction with the chair skeleton. The obvious similarity of the preferred transition state structures of the Claisen-Ireland rearrangements of Figures 11.44 and 11.43 causes the same fnms-selectivity. 

Fig. 11.45. Irani-selective Claisen-Ireland rearrangements with 1,4-chirality transfer. (See Figures 10.42 and 10.43, respectively, with R = vinyl in both cases, for preparations of the starting materials syn-A and anti-A, respectively.)...

Fig. 11.46. Claisen-Ireland rearrangements with simple diastereoselectivity.

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). 

Ireland rearrangement of the unsaturated macrolide (288) in THF/HMPA (3 1), followed by desilyl-ation in aqueous hydrogen fluoride in acetonitrile, led in 70% yield to a 72 28 mixture of acids (289) and (290) (Scheme 51). The intermediate silylketene acetal was found to be a single isomer, therefore both transition states (291) and (292) seem to participate in product formation (Figure 6). 

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