Stereoselectivity enantioselective intramolecular

Stereoselective Acylations. Intramolecular Ftiedel-Crafts acylation reaction of A/-ataLkyl a-amino acid detivatives gives cycHc ketones with high enantioselectivity (100). This methodology has been used for the enantiospeciftc syntheses of tylophorine [482-20-2] and cryptopleutine [87302-53-2] the ptincipal representatives of phenanthroiadolizidine and phenanthroquiaolizidine alkaloids (qv) (101). 

Major advances have been made in enantioselective intramolecular C-H insertion in a relatively short space of time. Because of the superiority of rhodium catalysts over copper catalysts for C-H insertion, the focus has been very much on development of chiral versions of the former. Both the structure of the diazo precursors and the ligands on the catalyst can have a profound influence on di-astereoselectivity and enantioselectivity, two important determinants on the efficacy of C-H insertion in stereoselective synthesis. Chemoselectivity is another control feature on which catalyst design can have a major influence. 

Enantioselective intramolecular cyclization of secondary phosphines 216 or their boranes, catalyzed by chiral palladium(diphosphine) complexes, afforded P-stereogenic benzophospholanes 217 with moderate stereoselectivity (59-70% ee) and yields. However, the absolute configuration of compounds has not been established. This reaction allowed chiral phospholanes to be obtained, which are valuable ligands in asymmetric catalysis (Scheme 70) [115]. 

Much of the recent hteiature on the mechanism of the enantioselective intramolecular Mizoroki-Heck reaction has focused on the anionic mechanism, o-iodoanilide substrates, pathways involving neutral pentacoordinate palladium intermediates and the influence of additives. The new examples and mechanistic findings indicate that the potential may exist to control the stereoselectivity of the intramolecular Mizoroki-Heck reaction through pathways other than the cationic mechanism. However, further research is needed to obtain the level of effectiveness of the traditional cationic pathway. 

One factor that the mechanistic scheme does not address is the change in stereoselectivity observed for the reaction of o-iodoanilides upon the addition of silver salts (Scheme 12.8). Recently, the influence of additives on the enantioselective intramolecular Mizoroki-Heck reaction of o-iodoaniUde 39 was studied in a series of reactions in which reaction times, temperatures, concentration and catalyst/Ag3P04 loading were varied [19]. It was observed that, in the presence of Ag3P04, the enantioselectivity of the product 40 increased... 

The introduction of the activated allylic bromides and Morita-Baylis-HiUman acetates and carbonates pioneered the development of a number of phosphine-catalyzed reactions in subsequent years [45]. Interestingly, the asymmetric variant of this type of transformation only appeared in the literature seven years later. In 2010, Tang, Zhou, and coworkers disclosed a highly enantioselective intramolecular ylide [3-1-2] annulation using spirobiindane-based phosphine catalyst 31 (Scheme 20.27). BINAP was found inactive in this reaction even at an elevated temperature (70°C). Notably, both optically active benzobicyclo[4.3.0] compounds 32 and 32 with three continuous stereogenic centers could be obtained as major products in high yields and stereoselectivities just by a choice of an additive [Ti(OPr )4], which can block the isomerization of the double bond [46]. 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

A new noncarbohydrate-based enantioselective approach to (—)-swainsonine was developed in which the key step was an aqueous intramolecular asymmetric hetero-Diels-Alder reaction of an acylni-troso diene (Eq. 12.57).128 Under aqueous conditions there was significant enhancement of the trans stereoselectivity relative to the reaction under conventional nonaqueous conditions. 

N-donor ligand. The reaction appears to proceed via an acyclic iminoplatinum(II) intermediate that undergoes a subsequent intramolecular cyclization. Some mechanistic aspects of this versatile reaction have been elucidated.225,226 A4-l,2,4-oxadiazolines have been prepared by the [2+3] cycloaddition of various nitrones to coordinated benzonitrile in m-[PtCl2( D M SO)(PhCN)] precursors.227,228 Racemic and chiral [PtCl2(PhMeSO)(PhCN)] complexes have also been used in order to introduce a degree of stereoselectivity into the reaction, resulting in the first enantioselective synthesis of A4-l,2,4-oxadiazolines, which can be liberated from the complexes by the addition of excess ethane-1,2-diamine. 

Using the results of an earlier study concerning enantioselective copper-catalyzed intramolecular C—H insertion of metal carbenoids,109 an interesting system for optimizing the proper combination of ligand, transition metal, and solvent for the reaction of the diazo compound (75) was devised (see Scheme 19).110 The reaction parameters were varied systematically on a standard 96-well microtiter/filtration plate. A total of five different ligands, seven metal precursors, and four solvents were tested in an iterative optimization mode. Standard HPLC was used to monitor stereoselectivity following DDQ-induced oxidation. This type of catalyst search led to the... 

Stereoselective intramolecular oxymercuration of carbohydrate derivatives was proposed as the key reaction for efficient preparation of mono- and dihydroxylated unsymmetrical bis-tetrahydrofuran skeletons present in naturally occurring biologically active acetogenins. The trans- and. mz-selective intramolecular oxymercurations were explored in an enantioselective synthesis of the bis-tetrahydrofuran skeleton of mucoxin (Fig. 57).73... 

Trons-divinyl-pyrrolidines and -piperidines were prepared by sequential intermolecular and intramolecular aminations of bis-allylic carbonates (Scheme 9.21) [22aj. Due to double stereoselection, these reactions proceeded with high diastereoselectivity and enantioselectivity. 

Section 2 discusses the syntheses of different classes of concave acids and bases. Convergent synthetic strategies were chosen for an easy structural variation of the reagents (modular assembly). Section 3 characterizes the concave acids and concave bases and checks whether the acid/base properties of the parent compounds benzoic acid, pyridine and 1,10-phenanthroline are conserved in the bimacrocyclic structures. In Section 4, the influence of the concave shielding on the reactivity and selectivity of the concave reagents is measured in model reactions. In principle, the concave shielding should be able to influence inter- and intramolecular competitions as well as chemoselectivity and (dia)stereoselectivity. If the reagent is chiral, enantioselectivity should also be observable. 

---