Regiochemical selectivity

When topological strategies are used concurrently with other types of strategic guidance several benefits may result including (1) reduction of the time required to find excellent solutions (2) discovery of especially short or convergent synthetic routes (3) effective control of stereochemistry (4) orientational (regiochemical) selectivity (5) minimization of reactivity problems and (6) facilitation of crucial chemical steps. 

N-Metalated azomethine ylides generated from a-(alkylideneamino) esters can exist as tautomeric forms of the chelated ester enolate (Scheme 11.8). On the basis of the reliable stereochemical and regiochemical selectivities described below, it is clear that the N-metalated tautomeric contributor of these azomethine ylides is important. Simple extension of the above irreversible lithiation method to a-(alkylideneamino) esters is not very effective, and cycloadditions of the resulting lithiated ylides to a,(3-unsaturated carbonyl compounds are not always clean reactions. When the a-(alkylideneamino) esters bear a less bulky methyl ester moiety, or when a,(3-unsaturated carbonyl compounds are sterically less hindered, these species suffer from nucleophihc attack by the organometalhcs, or the metalated cycloadducts undergo further condensation reactions (81-85). 

The addition of Grignards and organolithium reagents proceeds by attack at the metal center in ir-allylpalladium complexes. The regiochemical selectivity exhibited by these hard carbon nucleophiles with ir-allyl complexes substituted at the termini with alkyl or aryl groups is comparable to the soft carbon nucleophiles (ligand attack) in most cases, with addition occurring predominantly at the less substituted terminus (equations 248 and 249).1591387... 

A syndiesis of the hypocholesterolemic agent (+)-compactin centers around the Diels-Alder reaction of the chiral diene (282) with die chiral dienophile (281), which provided in a single operation die carbon framework of the target molecule (Scheme 67). However, facial and regiochemical selectivities of the additions were only moderate, giving rise to the formation of two legioisomers (283) and (284) the major product (283) was transformed into (+)-compactin. 

The 4-nitrophenyl ether group can be used to provide good regiochemical selectivity. A simple change to the ligand backbone changed the major product regioisomer (Scheme 3.42) [366]. 

Thioketones of various types are readily available and are well documented as effective dienophiles. Representative thioketone cycloadditions are listed in Table 5-1. In general, it appears that thioketones usually add to most dienes in high yield at exceptionally low temperatures to afford stable adducts, although some of these adducts tend to undergo retro-Diels-Alder reactions. - Very little has been done toward establishing the regiochemical selectivity of thioketone additions to unsymmetrical 1,3-dienes, and the few such entries in Table 5-1 indicate that mixtures were obtained. The exo/endo stereochemistry of [4 + 2] cycloadditions with unsymmetrical thioketones has not been probed to date. It has been reported that Diels-Alder cycloadditions of thioketones can also be pho-tochemically induced. 

You are now ready to proceed with the problems in this workbook. To bring all the models required for a particular problem onto the screen, you first need to enter the proper chapter folder ( Chapterl , Chapter ,. ..) and then select the appropriate problem, e.g., 05 Formal Charges from Chapter 1 . A few problems require two screens of models, e.g., 07 Regiochem of Additions from Chapter 7. Here the first screen is labeled A and the second B , e.g., 07 Regiochem of Additions A . 

The differences in the steric effect between catecholborane and pinacolborane, and the valence effect between a cationic or neutral rhodium complex reverse the re-gioselechvity for fluoroalkenes (Scheme 1-4) [26]. The reaction affords one of two possible isomers with excellent regioselectivity by selecting borane and the catalyst appropriately, whereas the uncatalyzed reaction of 9-BBN or SiaiBH failed to yield the hydroboration products because of the low nucleophilicity of fluoroalkenes. The regiochemical preference is consistent with the selectivity that is observed in the hydroboration of styrene. Thus, the internal products are selectively obtained when using a cationic rhodium and small catecholborane while bulky pinacolborane yields terminal products in the presence of a neutral rhodium catalyst. 

A regiochemical outcome of a palladium-catalyzed direct C-H bond functionalization of the pyrrole ring can be directed by choice of IV-substitution with bulky groups directing to C-3. The oxidative alkenylation of (V-(Boc)pyrrole led selectively to a 2-vinylpyrrole whereas the same reaction with the (V-(TIPS)pyrrole produced a 3-vinylpyrrole <06JACS2528>. 

Selective stereochemical and regiochemical combination of the geminate primary pairs. 

Crotti and co-workers work on regiochemical control of ring opening of epoxides by means of chelating agents has continued. Under standard conditions the regio-isomeric C(l) derivatives are the sole products from the trans epoxides (22a) and (22b) and are the predominant products from the cis epoxides (23a) and (23b). Under chelating conditions the cis epoxides unexpectedly show a consistent increase in C(2) selectivity. The results are discussed in terms of electronic and steric effects. 

---