Pyrrolidines bicyclic catalysts

An enantioselective variant of the diene cydization reaction has been developed by application of chiral zirconocene derivatives, such as Brintzinger s catalyst (12) [10]. Mori and co-workers demonstrated that substituted dial-lylbenzylamine 25 could be cyclized to pyrrolidines 26 and 27 in a 2 1 ratio using chiral complex 12 in up to 79% yield with up to 95% ee (Eq. 4) [ 17,18]. This reaction was similarly applied to 2-substituted 1,6-dienes, which provided the analogous cyclopentane derivatives in up to 99% ee with similar diastereoselectivities [19]. When cyclic, internal olefins were used, spirocyclic compounds were isolated. The enantioselection in these reactions is thought to derive from either the ate or the transmetallation step. The stereoselectivity of this reaction has been extended to the selective reaction of enantiotopic olefin compounds to form bicyclic products such as 28, in 24% yield and 59% ee after deprotection (Eq. 5) [20]. 

This observation has led to the preparation of more effective bicyclic oxaza-borolidines such as 1, prepared from (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine and BH3 (la) or methylboronic acid (lb). Both reagents catalyze borane reduction of alkyl aryl ketones to furnish (R)-alcohols in > 95% ee, by face-selective hydride transfer within a complex such as B. Catalyst lb is somewhat more effective than... 

As seen above with the phosphate receptors, researchers are often not satisfied with only binding their targets, but they also want to mimic enzymes and produce some catalytic activity from their receptors. De Mendoza and collaborators used the bicyclic guanidinium 47 to effect the addition of pyrrolidine to a,p unsaturated lactones [79]. Using a 10% catalyst loading in chloroform, an eightfold reduction in the half-life of the starting materials was observed by... 

Both complexes 12 and 13 are active toward atom-transfer cyclization of N-allyltrichloracetamides [40]. Of particular interest is the synthesis of a pyrrozi-lidine alkaloid skeleton. Much milder conditions are needed when using ruthenium-based catalysts instead of copper derivatives, although a high catalyst loading (30 mol %) is still required. Thus, an N-functionalized vinyl pyrrolidine is smoothly converted at room temperature into a bicyclic lactam, in 90% and 85% yield with complexes 12 and 13, respectively. The product is a precursor of the pyrrozilidine alkaloids trachelantamidine and pseudohehotridane (Eq. 10). 

Scheme 77). The product 239 was converted to (+)-pyrrolidine-197B 240. The tandem hydroamination/ cyclization of the allenylalkenylamine 241 occurred in the presence of the samarium catalyst 201 to give the bicyclic pyrrolizidine 242 in a high yield (Scheme 78). Hydrogenation of 242 led to (+)-xenovenine 243. 

Asymmetric nitro-Michael reactions of methyl vinyl ketone (MVK) in the presence of bicyclic guanidine with a benzhydryl group led, disappointedly, to low asymmetric induction (9-12%) [21a] Trials for the reaction of 0 ,p-unsaturated y- or 8-lactones with pyrrolidine in the presence of the conjugate acids of a bicyclic guanidine [50] or the Murphy s guanidine [24a] (R = Me in Scheme 4.7) resulted in the production of racemic compounds. The latter phase transfer catalyst (PTC) catalyses the nitro-Michael addition of chalcone but with limited range (70% yield, 23% ee) [24c]. 

In 1997, the same group disclosed an example of highly enantioselective C—H bond oxidation reactions. As shown in Scheme 1.61, conformationally fixed 3-oxa-bicycle[3.3.0]-octane 156 was oxidized at the a position under the catalysis of the Mn catalyst C25 ligated by a BINOL-derived salen ligand. Subsequently, the same group further expanded the scope to a meso-pyrrolidine derivative (up to 76% ee) and a meso-tetrahydrofuran derivative (up to 90% ee). Later,... 

The intramolecular reaction of bicyclobutane-ene 17, catalyzed by [RhCl(CH2=CH2)2]2 PPh3, led to the formation of pyrrolidine 18 as the major product (Scheme 2.21). On the other hand, in the presence of a catalyst prepared from [RlCl(CO)2]2-DPPE, (DPPE = l,2-bis(diphenylphosphino)ethane) the reaction resulted in exclusive formation of azepine 19 [32]. This selectivity is determined by the step that forms (allylcarbene)rhodium intermediates from the bicyclic rhodacycle. 

In this reaction, the tethered alkene functionality of the aniline derivatives form a Tr-allyl complex with the Pd(II) catalyst, and then the cyclization takes place via intramolecular nucleophilic attack by the N to form another Pd-complex, which reacts with CO as the electrophilic carbon source in the presence of MeOH to afford substituted bicy-clic pyrrolidine derivatives. However, these products were not stereoselective in nature. A similar type of Pd-catalyzed nonstereoselective cyclizations were also reported by Weinreb et al. and by Larock and Yang for the construction of bicyclic and bridged aza-cycles." ... 

The synthesis of bicyclic pyrrolidines has also been reported by the same group via the reaction of tethered iV-substituted cyclopentenyl amine with aryl bromide in the presence of the Pd2(dba)3 catalyst, phosphine ligand, and NaOf-Bu as the base (Scheme 40.6). " ... 

Scheme 17.15 Bicyclic pyrrolidine catalysts and the corresponding enantiomeric excess computed using transition state modeling. The higher and lower ee s are indicated.

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