Lewis acids bulky substituents

Alkyl-l,4-bis(4-tolylsulfonyl)-l,2,3,4-tetrahydropyridines 196, which can be synthesized from chiral (V-tosylazir-idines 195, are versatile compounds that can be converted into numerous piperidine and tetrahydropyridine species (Scheme 51). Nucleophilic substitution of the 4-tosyl group of 195 requires addition of a Lewis acid. Bulky substituents at the 2-position give 2,-4-anti- 1,2,3,4-tetrahydropyridine 197 while with smaller substituents a mixture of syn- and anti-isomers is formed <2001TL8369>. 

Sterically bulky 3,3 substituents reduced the enantioselectivity, while coordination between La and O atoms of ortho-substituents improved ees. 6,6 -diphenyl-BI-NOL gave the best results (69% ee for para-tolualdehyde) it was proposed that the phenyl substituents affected the Lewis acidity of the catalyst via electronic effects. With this catalyst, ee and yield depended strongly on solvent, THE being the most... 

The scheme below depicts the novel use of a carbonyl ene cyclization (A, Lewis acid-catalyzed) and a closely related Prins cyclization (B, Brpnsted acid-catalyzed) to generate predominantly trans (cyclization condition A) or cis (cyclization condition B), di and tri substituted piperidines 160 and 161 <06JOC2460 06OBC51>. Of note, in the formation of di-substituted derivatives, R1 = H and R2 = Ph, no reaction occurs under cyclization condition B and the cis isomer 160 is obtained exclusively under cyclization condition A. In the case of tri-substituted derivatives, when bulky substituents at the 2-position (R1 = f-Bu or Ph) are present the trans diastereomer 161 is obtained almost exclusively under cyclization condition A, while no diastereoselectivity is seen under cyclization condition B. 

Steric interactions between bulky substituents such as t-Bu, leading to larger C-E-C bond angles, obviously affect the Lewis basicity caused by the increased -character of the electron lone pair. However, the strength of the Lewis acid-base interaction within an adduct as expressed by its dissociation enthalpy does not necessarily reflect the Lewis acidity and basicity of the pure fragments, because steric (repulsive) interactions between the substituents bound to both central elements may play a contradictory role. In particular, adducts containing small group 13/15 elements are very sensitive to such interactions as was shown for amine-borane and -alane adducts... 

Catalysis of Claisen rearrangements has been achieved using highly hindered bis(phenoxy)methylaluminum as a Lewis acid.156 Reagents of this type also have the ability to control the E Z ratio of the products. Very bulky catalysts tend to favor the Z-isomer by forcing the a substituent of the allyl group into an axial conformation. 

In reactions between Lewis acids and bases such as amines and boranes or boron halides, bulky substituents on one or both species can affect the stability of the acid-base adduct. Perhaps the most straightforward type of effect is simple steric hindrance between substituents on the nitrogen atom and similar large substituents on the boron atom. Figure 9.3 is a diagrammatic sketch of the adduct between molecules of tripropylamine and triethylborane. This phenomenon is known as front or F-... 

The addition of donors to the Lewis acidic sp2-hybridized silicon in Si=N systems is a general method to stabilize the multiple bond, even when non-bulky substituents are used. In most cases the donor adduct reacts just like the free Si=N compound, obviously by initial dissociation of the donor molecule. In the absence of trapping agents and when the steric bulk allows it, silanimines dimerize300,308,311, e.g. 672 gives cyclodisilazane 789 (equation 265). 

In three-component allyltin-mediated processes, if the alkenes contain a chiral auxiliary, the allylation step proceeds with a high degree of stereocontrol [35]. In an example in Scheme 6.20, an acrylated oxazolidinone having a chiral substituent in the ring is employed as the alkene portion. Magnesium bromide is used as a Lewis acid to fix the acrylate moiety [36]. Allylation takes place diastereoselectively so as to avoid the face in which the bulky diphenylmethyl group is located. 

For both modern reagents PIFA and MoCls an inner-sphere radical transfer is expected, as depicted in Scheme 7. The Lewis acidic additives involved in the PIFA-mediated transformation create an iodonium species that forms a Jt-com-plex 26 with the substrate this subsequently leads to an electron transfer. In contrast, the electrophilic molybdenum chloride most probably coordinates to the oxygen atoms of the donor functions which will then start the transformation. Smooth conversions are obtained if the substituent R" adjacent to the donor (27) is another methoxy group or a bulky moiety. 

The presence of jr-electron-donating substituents at the 2-position of the vinyl portion of the ether allows for significant acceleration of the Claisen rearrangement.314-318 Aliphatic Claisen rearrangements can proceed in the presence of organoaluminum compounds,286-319-320 although other Lewis acids have failed to show reactivity.286,321 324 Useful levels of (Z)-stereoselection and asymmetric induction have been obtained by use of bulky chiral organoaluminum Lewis acids.325 327... 

Of interest is the fact that a Lewis acid with bulky substituents, such as methylaluminium di(2,6-di-t-butyl-4-methylphenoxide), also has an accelerating effect on the polymerisation of /1-lactone, the extent of acceleration being dependent on the mode of lactone ring cleavage. The polymerisation of /i-butyrolactone in the presence of (tpp)AlOMe [scheme (9)] was slower than that in the presence of (tpp)AlCl [scheme (10)], but the accelerating effect of the bulky Lewis acid was more significant for the (tpp)A10Me catalyst [125]. Thus, the acceleration effect is considered [125] to be due to the coordination of... 

---