Vedejs model

The stereochemical outcome of the Wittig reaction is believed to be the result of steric effects that develop as the phosphonium ylide and the aldehyde approach one another. A few transition state models have been proposed by Schlosser [29], McEwen [30, 31], and Vedejs [27, 28, 32]. Among them, the Vedejs model best accounts for the stereoselectivity on the basis of an interplay of 1,2- and 1,3-steric interactions in the four-center transition state (Scheme 3). The addition of the nonstabilized phosphonium ylide to the aldehyde proceeds through an early transition state that is fairly flexible. A preferred geometry for the cis transition state is... 

Scheme 3 Transition state structures according to the Vedejs model...

According to the density functional theory (DPT) calculations of the salt-free Wittig reaction performed by Aggarwal and Harvey et al. [33, 34], the puckering ability of the transition states in the Vedejs model does not depend on ylide stabilization. In the case of nonstabiUzed and semistabilized phosphonium ylides, the geometry of the transition states is decided by an interplay of 1,2-, 1,3-, and C-H O interactions. In contrast, a dipole-dipole interaction governs the transition state structures for stabilized phosphonium ylides. 

Another stereochemical aspect of these Diels-Alder reactions which has been studied by the Vedejs group is the facial selectivity in cycloadditions of chiral thioaldehydes. For instance, thioaldehyde (184), generated by the photochemical method, added to cyclopentadiene to give exo adducts (185) and (186) Jong with endo isomers (187) and (188) (Scheme 24). As was the case for achiral thioaldehydes, the endo adducts predominated (-9 1). The facial selectivity obtained can be rationalized via a Felkin-Anh or Comforth model for asymmetric induction. 

Angular hydroxylation.1 Vedejs hydroxylation of 1 affords 2 (62% yield), which is a model for the antibiotic bicyclomycin (3), obtained from S. sapporonensis. 

Vedejs and co-workers " ° applied CeHsSiHa/CsF reduction methodology of oxazolium salts as a means to access the indoloquinone ring present in aziridino-mitosene 1109. In a model smdy," the oxazolium salt 1111 was readily prepared... 

In later work, Vedejs and Piotrowski" expanded the model study to prepare an advanced tricyclic intermediate containing the complete carbon skeleton of 1109. In this case, the authors generated an intramolecular oxazolium salt to achieve their goal. Thus a mixture of 4-chlorobutyronitrile and diazo ketone 1116 was added to... 

Vedejs and Barda adapted Schollkopf s methodology " and prepared an indole-oxazole C-D-E model fragment, which was subsequently incorporated into a more advanced C-D-E-G-1 fragment. 4-Benzyloxyindole was converted to 1496 in four steps and excellent overall yield (Scheme 1.383, p. 337). Treatment of 1496 with lithiomethyl isocyanide produced a 2 1 mixture of the acylisocyanide (not shown) and 1497. Reaction of this mixture with PPTS cleanly provided the C-D-E model fragment, 1497. The triflate 1497a was then prepared in three straightforward steps. 

Vedejs et al., on the basis of both DFT calculations and of X-ray diffraction analysis of compound 6, proposed a qualitative model for the stereochemical induction observed with this catalyst [18b]. These authors conjectured that in the transition state of the Steglich and related rearrangements, to minimize the steric interactions, the endocyclic oxygen of the azlactone is oriented towards the acetoxy group and that the C4-substituent is placed between the two oxygens of the phe-noxycarbonyl group (Figure 40.1). This model would account for the preferred C4 Re-face attack observed with catalyst (R)-6. >... 

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