Control of Diastereoselectivity

Danishefsky et al. [9] reported that stereochemical outcome of cyclocondensation of aldehydes and siloxy dienes was highly dependent on the nature of Lewis acid catalysts. When the reaction of diene 1 and benzaldehyde 2 was performed using BF3 OEt2 consistent tram (threo) selectivity was observed (cis-3/trans-3 = 13) (Sch. 1). High cis specificity was, however, observed in the presence of MgBr2 or ZnCl2 cisitrans = 38 1 and 39 1, respectively). 

This diastereoselectivity was explained as follows. The reactions catalyzed by MgBt2 or ZnCl2 were true pericyclic reactions via an all-carbon framework of the classical Diels-Alder processes. The phenyl group of benzaldehyde, bound to the Lewis acid, was located in an endo orientation I relative to the diene (Sch. 2). Intermediate 4 from the pericyclic pathway with the cis stereochemistry at the 5- and 6-positions, which was actually isolated, was smoothly converted to the final cis pyrone 3 by treatment with trifluoroacetic acid [10]. 

A f/ireo-selective siloxonium (aldol-like) pathway II was favored when BF3 OEt2 was used as catalyst (Sch. 3) [11]. The reaction of benzaldehyde by quenching after 5 min resulted in 48 % yield of the final cyclic products 3 (1 8 cisitrans ratio) and 46 % yield of the Mukaiyama-like aldol products 5 (1 2 threolerythro ratio). When either threo or erythro adduct was re-subjected to trifluoroacetic acid media, each underwent conversion to the corresponding y-pyrones 3. 

In the reaction of a-alkoxyaldehydes the stereochemical outcome is different— reactions in the pericyclic mode now lead preferentially to the 5,6-anti product. The reaction of chiral a-benzyloxyaldehyde 6 under the influence of MgBr2 afforded a single pyrone 7, which was consistent with a chelation-control product [9b,12]. A chelated complex was formed, and the exo transition state III was preferred because of steric repulsion between the diene and the chelated ring (Sch. 4). 

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Alternatively, substrate control of diastereoselectivity can rely on attractive catalyst substrate interactions. This requires in general special functional groups which allow for a directed hydroformylation, which is summarized in Sect. 6 (vide infra). 

Telfer, S. G. Yang, X.-J. Williams, A. F. Complexes of 5,5 -aminoacido-substituted 2,2 -bipyridyl ligands Control of diastereoselectivity with a pH switch and a chloride-responsive combinatorial library. J. Chem. Soc. Dalton Trans. 2004, 699-705. 

This distinction is important because exo and endo transition states lead to different diastereomers. Control of diastereoselection is extremely important to... 

Scheme 3. Design of a catalyst-directing group for the control of diastereoselectivity upon hydroformylation of acyclic methallylic alcohols.

One may improve efficiency of an o-DPPB directed hydroformylation by incorporating this reaction into sequential transformations (domino reactions) [16]. The hydroformylation itself should be ideally suited for such a purpose, since this reaction provides under fairly mild reaction conditions access to the synthetically valuable aldehyde functionality. The aldehyde itself should be ideally suited to allow for further skeleton-constructing reactions. One type of sequential transformations employing the hydroformylation reaction as a key step is the hydroaminomethylation of olefins originally discovered by Reppe [17]. However, efficient control of diastereoselectivity in the course of this hydroaminomethylation reaction was unknown [18, 19]. 

Fig. 3.26. cis-Selective hydration of a chiral, racemic, trisubstituted alkene with induced diastereoselectivity A corresponds to the extent of the substrate control of diastereoselectivity. 

Fig. 3.30. Asymmetric hydration of an achiral alkene via hydroboration/oxidation/hydro lysis AFa corresponds to the extent of reagent control of diastereoselectivity.

If, as in the reaction example in Figure 3.32, during the addition to enantiomerically pure chiral alkenes, substrate and reagent control of diastereoselectivity act in opposite directions, we have a so-called mismatched pair. For obvious reasons it reacts with relatively little diastereoselectivity and also relatively slowly. Side reactions and, as a consequence, reduced yields are not unusual in this type of reaction. However, there are cases in which mismatched paris still give rise to highly diastereoselective reactions, just not as high as the matched pair. 

Conversely, the addition of enantiomerically pure chiral dialkylboranes to enantiomerically pure chiral alkenes can also take place in such a way that substrate control and reagent control of diastereoselectivity act in the same direction. Then we have a matched pair. It reacts faster than the corresponding mismatched pair and with especially high diastereoselectivity. This approach to stereoselective synthesis is also referred to as double stereodifferentiation. 

Thought Experiments II and III on the Hydroboration of Chiral Olefins with Chiral Boranes Reagent Control of Diastereoselectivity, Matched/Mismatched Pairs,... 

The control of diastereoselectivity in the allylation reaction of carbonyl compounds with allylic indium reagents has been an important issue since the discovery of the indium-mediated carbonyl allylation. As earlier discussions have been summarized in the precedent reviews,6-24 only relatively recent references are cited below. 

J. L. Chiara and A. Garcia, Control of diastereoselectivity in C=0/C=N reductive cyclization using an intramolecularly tethered hydrazone, Synlett, 17 (2005) 2607-2610. 

In the synthesis of ( )-homononactic acid, a -selective iodoetherification was achieved with complete control of diastereoselectivity (Equation 77) <1996SL777>. 

For the sake of comparison, the regio- and stereo-selectivity of some nucleophilic openings of vinyl-oxiranes with organometallic reagents derived from copper, lithium, sodium and other metals indicate the control avail le under some conditions. Complete control of diastereoselectivity in the opening of cyclic vinyloxiranes is available, for example by utilizing palladium(0)-catalyzed conditions in the reaction of die sodium salt of dimethyl malonate with cyclic vinyloxiranes.Increased substitution on the vinyl portion of the vinyloxirane leads to isomerization with opening, as in the case of the disub-stituted vinyloxirane (150 equation 49). ... 

Adam, W., Stegmann, V. R. Unusual Temperature Dependence in the cis/trans-Oxetane Formation Discloses Competitive Syn versus Anti Attack for the Patemo-Buchi Reaction of Triplet-Excited Ketones with cis- and trans-Cyclooctenes. Conformational Control of Diastereoselectivity in the Cyclization and Cleavage of Preoxetane Diradicals. J. Am. Chem. Soc. 2002,124, 3600-3607. 

W. Adam, T. Wirth, Hydroxy group directivity in the epoxidation of chiral allylic alcohols Control of diastereoselectivity through allylic strain and hydrogen bonding, Acc. Chem. Res. 32 (1999) 703. 

Table 7 summarizes several important aspects of substrate control of diastereoselectivity. Variation of either the relative configuration of the lactone or of the olefin geometry allows access to the opposite diastereochemical series (Table 7, entries 2-5)80. Since only the ( )-olefins are formed, a successful chirality transfer either requires ionization of the lactone from a single conformation B with nucleophilic attack being faster than stereorandomization or an involvement of solely the, mi,.n -7t-allyl complex generated via n-a-n rearrangement prior to C —C bond formation. The soft carbanion attacks the allyl complex charge directed distal to the carboxylate anion. 

Access to a number of fused thiophene based structures has been gained via intramolecular C-H insertions adjacent to sulfur with control of diastereoselectivity. Thus for instance. 

Furukawa and coworkers have used paUadium/BINAP complexes to catalyse 1,3-dipolar cycloaddition of nitrones to alkenes and whilst enantioselectivity is high (up to 91% ee), control of diastereoselectivity (e do versus exo) is poor. ... 

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