Schlosser conditions

During the stereospecific total synthesis of (7S,15S) and (7R, 15S)-dolatrienoic acid by G.R. Pettit et al., the C7-C10 and C11-C16 subunits were coupled using the highly ( )-selective Wittig-Schlosser reaction The traditional Wittig conditions resulted in a mixture of alkenes in which the (Z)-stereoisomer was predominant. When the Schlosser conditions were applied, the stereoselectivity was reversed in favor of the ( )-alkene. 

For the synthesis of sulfobacin A (158) and flavocristamide A (160), TBS ether of (f )-3-hydroxy-15-methylhexadecanoic acid was necessary, which was synthesized from 10-bromo-l -decanol (A) as shown in Figure 6.20. Chain elongation of A under the Schlosser conditions gave B, which was oxidized with PCC to give aldehyde C. ( )- 3-Hydroxy ester D was prepared from C by treatment with ethyl acetate and LDA. The corresponding ( )-acid was acetylated with vinyl acetate in the presence of lipase PS to give enantiomerically pure (R)-hydroxy acid and the acetylated (S )-acid. The former was converted to its TBS ether E. 

Toluene itself can be lithiated by w-BuLi-TMEDA at or above room temperature, and deprotonation occurs almost exclusively at the methyl group—about 10% ring metallation (mainly in the meta position) is observed with w-BuLi-TMEDA (Scheme 188) . At lower temperatures deprotonation is very slow , and the best conditions for achieving the metallation of toluene are the Lochmann-Schlosser superbases (see Section VI) °. 

The Schlosser-Marcus variational principle is derived for a single surface a that subdivides coordinate space 9i3 into two subvolumes rm and rout. This generalizes immediately to a model of space-filling atomic cells, enclosed for a molecule by an external cell extending to infinity. The continuity conditions for the orbital Hilbert space require i>out =a i>in This implies a vanishing Wronskian surface integral... 

A different reaction mode of lithiobetaines is used in the Schlosser variant of the Wittig reaction. Here, too, one starts from a nonstabilized ylide and works under non-salt-free conditions. However, the Schlosser variant is an olefination which gives a pure frans-alkene rather than a trans.cis mixture. The experimental procedure looks like magic at first ... 

This arbitrariness was noticed by Cohen and Heine and by Schlosser who suggested that one way of resolving the difficulty would be to place extra conditions on the pseudopotential operator. In particular they proposed that the eigenfunctions xm should be required to have the minimum possible radial kinetic energy ... 

As pointed out in this woric, the mild conditions of the Cr reaction resulted in no observed epimeriza-tion, and offered an excellent alternative to the Schlosser modification of the Witdg reaction. Both the C1CI2 chemistry and the TiCU/Zn method discussed in Section 3.1.12.1.2 have the advantage of preparing the metallocarbene complex in situ. 

The Wittig reaction was carried out by the Schlosser method - the ylid was generated with PhLi and the aldehyde added at low temperature (-70 °C). A second equivalent of PhLi was added and the intermediates allowed to equilibrate at -30 °C. Elimination of Ph3P=0 occurred under these conditions to give the E-alkene. Deprotection and aldol condensation gave the cyclopentenone in a very impressive 46% yield over the five steps from the original aldehyde. 

Prolonged interaction at room temperature between BuLi TMEDA and an excess of isobutene affords isobutenyllithium, as appeared from the results of subsequent reactions with electrophilic reagents [1]. When the metallation is carried out with a 1 2 molar ratio of isobutene and BuLi-TMEDA in hexane, mainly dilithiated isobutene is formed [2], Bates et al. [3] reacted isobutene with two mol equivalents of the Lochmann-Schlosser reagent in hexane and observed a much faster dimetallation. It should be pointed out that this dimetallation takes place under heterogeneous conditions and in the apolar, inert solvent hexane. Our attempts to achieve a more complete dimetallation by carrying out the reaction in the presence... 

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