Stereochemical control, importance considerations

In Chapter 12 we met some basic ideas on stereochemical control in synthesis. Now we reopen this important question and put into perspective the many stereospecific and stereoselective reactions we have met in the intervening chapters. Tables 38.1 and 38.2 give brief summaries. With so many methods at our disposal, a very considerable degree of stereochemical control is possible and stereochemistry is often a dominant factor in strategy. 

The relative frontier molecular orbital (FMO) energies of the reagents are very important for the catalytic control of 1,3-dipolar cycloadditions. In order to control the stereochemical outcome of a reaction with a substoichiometric amount of a ligand-metal catalyst, it is desirable that a large rate acceleration is obtained in order to assure that the reaction only takes place in the sphere of the metal and the chiral ligand. The FMO considerations will be outlined in the following using nitrones as an example. 

Over the past decade, the stereocontrolled reduction of enantiomerically pure P-ketosulfoxides by hydride reagents, particularly within the Solladid research group, has sparked considerable interest, as an approach to many synthetically important intermediates and biologically active molecules of defined chirality. The applications described below outline the effectiveness of the chiral sulfoxide moiety as a stereocontrol element, and highlight the ready removal of the sulfoxide group after its contribution to the synthetic scheme. In all cases, the sense of stereochemical induction can be rationalized and predicted on the basis of steric, stereoelectronic and/or chelation control factors. 

Intramolecular interactions involving the sulphur atom in cyclic sulphur compounds, sometimes with the formation of discrete sulphonium ion intermediates, have played an important role in determining the rate and stereochemical outcome of many reactions. Both steric and electronic factors were important in controlling the stereochemistry of the chlorination of various thiapropellanes by iV-chlorosuccinimide. For example, the ratio (65 35) of (39) to (40) obtained by chlorination of (41) was greater than the ratio (56 44) of (42) to (43) obtained from (44), although consideration of steric effects alone would have predicted the converse result. ... 

Cycloaddition reactions are also orbital symmetry-controlled, pericyclic reactions. We have seen one example already, the Diels-v lder reaction, and we will use it as our prototype. We found the Diels-Alder cycloaddition to be a thermal process that takes place in a concerted (one-step) fashion, passing over a cyclic transition state. Several stereochemical labeling experiments were described in Chapter 12 (p. 549), all of which showed that the reaction involved neither diradical nor polar intermediates. This stereospecificity is important because orbital symmetry considerations apply only to concerted reactions. Of course, all reactions can be subdivided into series of single-step, single-barrier processes, and each of these steps could be... 

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