Rigid cyclic substrates

E.3.2.2. Deracemization of Cyclic Substrates Although the ambiguity of synlanti geometry can be removed by the rigidity of the cyclic framework, the interaction between the ligand and a cyclic allyl substrate becomes quite different from that of acyclic systems because relatively... 

When a mineral or Lewis acid replaces the carboxylic component in the Passerini reaction, the final products are usually a-hydroxyamides. Also in this case, when chiral carbonyl compounds or isocyanides are employed, the asymmetric induction is, with very few exceptions, scarce [18, 19]. For example, the pyridinium trifluoroacetate-mediated reaction of racemic cyclic ketone 14 with t-butyl isocyanide is reported to afford a single isomer [19] (Scheme 1.7). This example, together with those reported in Schemes 1.3 and 1.4, suggests that high induction may be obtained only by using rigid cyclic or polycyclic substrates. 

This control, however, can be tested only in acyclic dienes, which lack of the conformational rigidity of cyclic substrates. Loss of the stereochemical information could be due to isomerization of the starting diene [18b,19c], to two-step processes [18], or to the reversible formation of an exciplex which, depending on the substrate structure, may have a zwitterionic and/or diradical character [19]. 

This discrepancy can at least be partially explained by taking into account that in chelation-controlled reactions the acyclic substrate is essentially locked into one rigid cyclic conformation. The reactants taking part in nonchelation-controlled additions have many more degrees of freedom, and exclusive reaction with one conformer is less likely. These reactions rely on reagents which are incapable of chelation and/or substrates containing sterically or electronically differentiated substituents. ... 

Yields in the Sml2-promoted intramolecular Reformatsky reaction are typically higher for ketones than for aldehyde substrates, but in both series diastereoselectivity is virtually complete. It has been suggested that reaction of Smh with the 3-bromoacetoxy initially generates a Sm ester enolate, with cyclization taking place through a rigid cyclic transition structure enforced by chelation (Scheme 4). ... 

The control of stereoselectivity in acyclic substrates is more difficult than in cyclic substrates. As discussed previously, palladium can serve as a template to provide rigidity in an acyclic system thus favoring higher stereoselectivity. Palladium(0)-mediated substitution of the chiral nonracemic ally acetate depicted below yields only racemic material68, n-o-n Rearrangement of the intermediate 7t-allyl complex involving the unsubstituted allyl terminus is probably faster than nucleophilic attack. 

There are a number of processes that can conpete with the di-n-rearrangement and related reactions. As indicated earlier, in the case of the parent DPM rearrangement, unproductive isomerization of the olefins within the substrate can occur when triplet-mediated conditions are applied to acyclic substrates. Electrocyclic processes can also conpete. For exanple, while acetophenone-sensitized irradiation of benzobarrelene (44) affords benzosemibullvalene (8), direct irradiation of the same substrate yields benzocyclooctatetraene (45) via a [2+2] photocycloaddition/cycloreversion sequence. Such electrocyclic processes tend to proceed preferentially from the singlet excited state and take place exceptionally rapidly. In broad terms, cyclic substrates are more likely to suffer from conpeting electrocyclic reactions by conparison with their acyclic counterparts, one reason being the entropic advantage conferred on such processes by more conformationally rigid frameworks. 

To study the effect of conformationally more rigid substrates, some cyclic allylic esters (23 and 24) were employed as substrates. Reaction of these with n-BuMgl, employing 19b as catalyst, produced very low ees, however (Scheme 8.19) [35]. 

---