Diastereoselectivity attractive interactions

Diels-Alder reaction of 2-bromoacrolein and cyclopentadiene using 10 mol% of titanium catalyst 74 gave the synthetically versatile (R)-bromoaldehyde adduct 75 in 94% yield, 67 1 exo. endo diastereoselectivity, and 93% ee. The absolute stereochemical outcome of the reaction is consistent with the proposed transition state assembly 76 in which the dienophile coordinates at the axial site of the metal, proximal to the indane moiety through Ji-attractive interactions. In this complex, the 7t-basic indole and the Ji-acidic dienophile can assume a parallel orientation facilitated by the octahedral geometry of the transition metal. The aldehyde would then react through a preferential s-cis conformation (Scheme 17.27).54... 

Scheme 7.19 Cation-n attractive interactions leading to highly diastereoselective ring expansion...

The tartrate-derived allyl and crotyl boronates 25 developed by Roush [33, 42-48] represent a convenient and elegant alternative to the terpene-derived boranes described above, as a consequence of their ease of handling and configurational stability (Equation 3). Representative examples are summarized in Table 5.2 [42, 45, 47]. These reagents have also enjoyed widespread applications in diastereoselective, reagent-controlled additions to chiral aldehydes, displaying superb levels of diasteroinduction [43, 44, 48], An explanation for the observed stereoselectivity has been proffered by Roush [32] and supported by ab initio calculations [62] minimization of lone pair/lone pair interactions as well as an attractive interaction between the ester lone pairs and the polarized aldehyde are believed to result in a preference for transition state structure 26. 

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

If the substituents are nonpolar, such as an alkyl or aryl group, the control is exerted mainly by steric effects. In particular, for a-substituted aldehydes, the Felkin TS model can be taken as the starting point for analysis, in combination with the cyclic TS. (See Section 2.4.1.3, Part A to review the Felkin model.) The analysis and prediction of the direction of the preferred reaction depends on the same principles as for simple diastereoselectivity and are done by consideration of the attractive and repulsive interactions in the presumed TS. In the Felkin model for nucleophilic addition to carbonyl centers the larger a-substituent is aligned anti to the approaching enolate and yields the 3,4-syn product. If reaction occurs by an alternative approach, the stereochemistry is reversed, and this is called an anti-Felkin approach. 

Alternatively, substrate control of diastereoselectivity can rely on attractive catalyst substrate interactions. This requires in general special functional groups which allow for a directed hydroformylation, which is summarized in Sect. 6 (vide infra). 

The analysis and prediction of the direction of preferred reaction depend on the same principles as for simple diastereoselectivity and are done by analysis of the attractive and repulsive interactions in the presumed transition state. 

The reactions of bare Fe" " ions and related species in the gas phase continue to attract much interest. The remote functionalisation of 1,6-hexanediol by Fe occurs by C-H activation at C(3) and C(4).26 Functionalisation of 3-methyl-2-pentanone at C(4) is diastereoselective, probably because of the conformation of a chair-like intermediate. Reactions of Fe with anisoles and phenols have also been studied.28 Interaction of Fe with silanes gives both silene and silylene species, though the two are not interconvertible. The reactions of Fe(alkene)+ complexes with pentane were found to differ dramatically from those of bare Fe" , and C-H and C-C activation were also observed in reactions of Fe(C2H4) with oxygen. 0,31 interaction of Fe(benzyne)+ with alkyl halides led to C-X or C-C addition followed by p-elimination and loss of HX.32 The gas phase reaction of Fe(NH2)Me" with C2H4 is best explained by insertion into the Fe-C bond followed by P-elimination and loss of propene. The reaction of FeMe with 1-octyne also leads to C-C bond forming processes. 

In the case of the diastereoselective cycloaddition starting from 117, calculations revealed that the selectivity observed arose from a stabilizing attractive edge-to-face CH-n interaction between the furan C-H and the 7i-aromatic ring in the... 

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