Anionic rearrangement synthetic utility

Aliphatic 3-aza-4-oxa-Cope rearrangement of ester-amide dienolates increases the synthetic utility of anionic [3,3]-sigmatropic rearrangement initiated by N—O bond cleavage. Treatment of the enehydroxylamine 94 with KHMDS in the presence of TMSCl at —80°C provided a mixture of iV,0-disilylated 95 and 0,0-disilylated 96 derivatives (equation 30). Both of these would, on [3,3]-sigmatropic rearrangement, provide the corresponding silyl ethers 97 and 98, from which 99 and 100 are obtained on workup. 

Allyl, pentadienyl, and heptatrienyl anions can in principle undergo electrocyclic rearrangements (81). The thermal conversion of a pentadienyl into a cyclopentenyl anion is predicted to be a disrotatory process. The cyclooctadienyl anion cyclizes to the thermodynamically stable isomer of the bicyclo[3.3.0]octenyl ion having cis fused rings (52,82,83). The acyclic pentadienyl anions, however, do not normally cyclize. On the other hand, heptatrienyl anions cyclize readily at — 30°C by a favorable conrotatory thermal process (41,84). This reaction sets a limit upon the synthetic utility of such anions. 

The synthetic utility of this annulation methodology is significantly enhanced by the fact that the cy-clopentenylmethyl sulfone anions generated in the rearrangement step can be tnq> in situ with a variety of organic electr hiles, and that desulfonylation can then be conveniently achieved in the same flask under mild conditions. The transformations outlined in Scheme 14 illustrate this strategy. Thus, re-... 

The K-alkoxide of the startg. m. prepared with KH in anhydrous tetrahydrofuran heated several min. at 66° product. Y 98%. - Both the increased yield and lower reaction temp, in this anionic oxy-Cope process should improve the synthetic utility of these and related rearrangements. F. e. s. D. A. Evans and A. M. Golob, Am. Soc. 97, 4765 (1975). 

Although the anionic oxy-Cope rearrangement of 47 served admirably as a means for accessing 50 and 52, the utility of the major tetracyclic product was not viewed with optimism. We identified a variety of options for central bond cleavage therein, but the steps needed to accomplish this chemistry were certain to result in appreciable lengthening of the synthetic undertaking. For these reasons, we turned our attention instead to the deployment of 45 as the precursor to the nucleophile of choice. 

In this chapter, we present unique aspects of the rearrangement with a focus on (1) the production of carbanions under mild conditions, (2) the generation of synthetically valuable enol silyl ethers that are often the products, (3) the potential for incorporation of die Brook rearrangement in tandem and sequential anion relay processes, and (4) the utility of the rearrangement in generating chiral, configurationally stable carbanions. 

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