Stereo- and regioselective organic transformations based on main group organometallic reagents- application to the stereocontrolled Claisen rearrangements

Unprecedented stereocontrolled Claisen rearrangement of allylic vinyl ethers has been developed with modified organoaluminum reagents A and B as an example of diastereoselective activation of ethereal substrates. The stereoselective activation of ether moiety is the subject of our current interest. Oxygenophilic organoaluminum reagents are known to exhibit the great tendency to form stable ether-aluminum complexes.1 Our expectation is the stereoselective activation of ethereal oxygen by selective coordination of one out of the two lone pair electrons of the oxygen atom to aluminum reagent. Here, when R and R are different, ethereal oxygen is prochiral and by the selective coordination to aluminum, this oxygen is now chiral. Hence, with chiral ethers diastereoselective activation of the ether oxygen would be possible, while combination of chiral organoaluminum reagents with prochiral substrates would enable enantioselective activation of ethers. Chiral Substrates Diastereoselective Activation Chiral A1 Reagents Enantioselective Activation First, we have examined our concept by applying it to the stereo-selective Claisen rearrangement. The Claisen rearrangement and its variants (Carroll, the ortho ester, Eschenmoser, and Ireland rearrangements)z provide an excellent stereoselective route to a$-unsaturated carbonyl compounds (aldehydes, ketones, esters, amides, and acids) from allylic alcohols, and offer a crucial step in the stereoand regiochemically defined synthesis of a wide variety of natural products.3 The reactions involve a [3,3]-sigmatropic rearrangement and take place by a concerted mechanism through a cyclic six-membered chairlike transition state.4 The principle value of these rearrangements in organic synthesis stems from the fact that they are highly stereoselective, particularly when X = H in ally1 vinyl ether 1, leading almost exclusively to the E-configuration of the newly created double bond. Examination of the two chairlike transition-state conformations as depicted in Scheme 1 reveals why the E-product ( E ) 3 invariably predominates. Conformation 2a, with the R substituent equatorial, leads to the (E)-olefinic aldehyde (E)-3, whereas the less likely conformation 2b, with the R axial, leads to the (Z)-olefinic aldehyde (Z)3. In fact, the strong preference for E-products has been observed for Claisen as well as Carroll, the ortho ester, Eschenmoser, and Ireland rearrangements, and is clearly a general attribute of the Claisen family. In simple Claisen rearrangement of 1 (X = H), the E/Z ratio in the product is approximately 90: 10,s but when X is larger than H, as in the Eschenmoser (X = NMe2), ortho ester (X = OEt), and Ireland (X = OSiR3) rearrangements, the E/Z ratio can be greater than 99:l due to the increased 1,3-diaxial interaction in the transition state 2b, which dramatically decreases its participation.6 Consequently, it is difficult to obtain the Z-selectivity by using conventional methodologies. In this context, we have been interested in the development of organo-aluminum-