Stereocontroling interaction, intramolecular

Figure 5-3 Stereocontrolling interactions in the intramolecular Pauson-Khand reaction.

The tandem radical cyclization of tetrayne (97) and its derivatives has been performed to generate the polycyclic pyran (98) via a biradical intermediate.238 The cycloaddition reaction of a biradical species (or diyl) and a multiply bonded species (the diylophile)239 has been observed with unique allene diylophiles.240 The short-lived biradical fonned by the irradiation of the diazene (99) is trapped by an allene diester to form a second biradical species (100). Intramolecular cyclization occurs such that all steric interactions are minimized and so enforces stereocontrol in the formation of the cycloadduct (101) see Scheme 14. A paper reports the rearrangement of 2-vinyhnethylenecyclopropane (102) to 3-methylcyclopentene (103) via the triplet biradical (104), which has been characterized for the first tune by IR spectroscopy.241... 

Another more efficient catalytic version of the reaction consists of the interaction of ketones with chiral amines [6] to form enolate-like intermediates that are able to react with electrophilic imines. It has been postulated that this reaction takes place via the catalytic cycle depicted in Scheme 33. The chiral amine (130) attacks the sp-hybridized carbon atom of ketene (2) to yield intermediate (131). The Mannich-like reaction between (131) and the imine (2) yields the intermediate (132), whose intramolecular addition-elimination reaction yields the (5-lactam (1) and regenerates the catalyst (130). In spite of the practical interest in this reaction, little work on its mechanism has been reported [104, 105]. Thus, Lectka et al. have performed several MM and B3LYP/6-31G calculations on structures such as (131a-c) in order to ascertain the nature of the intermediates and the origins of the stereocontrol (Scheme 33). According to their results, conformations like those depicted in Scheme 33 for intermediates (131) account for the chiral induction observed in the final cycloadducts. 

Calculations [46] and studies of intramolecular oxaziridinium epoxidations [47] suggest that, like their dioxirane counterparts, these epoxidation processes proceed via spiro-transition states. However, the iminium epoxidations are generally more substrate-specific than those using dioxiranes, and models to explain the observed trends in stereocontrol have proved more difficult to construct. One complication is the possibility of formation of diastereomeric oxaziridinium salts from most of the iminium catalysts. Houk has rationalized computationally the observed enantioselectivity with Aggarwal s catalyst 16 [46]. The results of a recent study by Breslow suggest that hydrophobic interactions are important in these processes [48], and aromatic-aromatic interactions between catalyst and substrate may also play a role. 

Fustero, S., Navorro, A., Pina, B., et al. (2001) Enantioselective synthesis of fluorinated a-amino acids and derivatives in combination with ring-closing metathesis intramolecular n-stacking interactions as a source of stereocontrol. Org. Lett., 3, 2621-2624. 

The influence of adjacent stereogenic centers on the diastereoselectivity of the cyclization is addressed in entries 4 13. Alkyl or aryl substituents in the homoallylic position lead only to a moderate preference for the 4,6-m-product (Table 14, entries 4 7)9. Surprisingly, the triflu-oromethyl group exerts complete stereocontrol, which is attributed to its steric and additional electronic repulsion of the enolate moiety in the cyclization transition state (for a detailed discussion see the preceding section). The intramolecular reactions of the bissulfone derivatives (Table 14, entries 11 -14)19 feature a contrathermodynamic production of mainly civ-substituted vinylcyclopentanes. Epimerization of the zr-allyl complex is faster than cyclization, so that an equilibrium between the different isomeric zwitterions is established. Due to unfavorable steric interactions with the substituent R, palladium is preferentially located irunx to R in the cyclization transition state favoring the m-product. The use of toluene, tetrahydrofuran, and acetonitrile as solvents results in poorer diastereoselectivities. Some restrictions apply to the kind of nucleophile employed, thus 2-oxo esters may only give the 0-alkylated product (cf. Table 12)2 19-20. 

The development, by Snider, of intramolecular cyclizations of unsaturated p-keio esters with Mn(III) and Cu(II) has been the souree of numerous and speetacular cascades [27]. Intrigued by the potential of this chemistry as a biomimetic approach to polycyclic systems, Zoretic [28] reported the tetracyclization of precursor 46 to provide tetracyclohexyl derivative 47, in which seven asymmetric centers have been established with complete stereocontrol (Scheme 16). This remarkable sequence deserves several comments. The regioselectivity 6-endo-tng) and diastereoselectivity of the initial cyelization is consistent with Snider s seminal studies notably the ester group adopts an axial position to minimize unfavorable dipole/dipole interactions with the ketone. The two subsequent 6-endo-lng cyclizations that can be rationalized by a slower 5-exo mode of cyelization involving a bond formation sandwiched... 

In this regard, the authors probed different substituents and stereochemistries, mainly in position 5, 6, and 9 of the pyranose core of 242-(Z), to explore the role of the stereoelectronic interactions [102-105], conformational restrictions [106-108], and formation of intramolecular hydrogen bonds in the stereocontrol of this reaction. For the anomeric effect, see [109]. For the anomeric effect of protons, see [110], and for the formation of intramolecular hydrogen bonds [111] in the stereocontrol of this reaction. 

---