Lewis acidity external

The most successful of the Lewis acid catalysts are oxazaborolidines prepared from chiral amino alcohols and boranes. These compounds lead to enantioselective reduction of acetophenone by an external reductant, usually diborane. The chiral environment established in the complex leads to facial selectivity. The most widely known example of these reagents is derived from the amino acid proline. Several other examples of this type of reagent have been developed, and these will be discussed more completely in Section 5.2 of part B. 

The electrophilicity of silicon is enhanced in five-membered ring structures. Chloro dioxasilolanes, oxazasilolidines, and diazasilolidines react with aldehydes in the absence of an external Lewis acid catalyst.113... 

HZSM-5 was used, the starting material (12) was recovered in 69% yield, a result most probably attributable to its more confined-pore structure. However, the highest regioselectivity for the furanoside/pyranoside form (14 1) was obtained with this medium-pore zeolite. It could also be concluded that the external surface area of the zeolites and the Lewis acid sites (Table II), do not have any effect on yield/ regioselectivity of this reaction. 

Also in macrocyclizations the conformation of the starting diene has an influence on the RCM/ADMET ratio. Substituents on the diene which form hydrogen bonds between each other or with the intermediate carbene complex, or external Lewis acids can have an important effect on the course of the reaction. Such effects, often subtle, might explain the variable results sometimes obtained in macrocyclizations [842], but make synthesis-planning and the formulation of general guidelines difficult. 

Most of the useful auxiliaries are chiral amine or alcohol derivatives readily available from the chiral pool, and most of them possess rigid cyclic or bicyclic structures to allow efEcient differentiation of the two competing diastereomorphic transition states. In some cases, additional rigidity was achieved with the aid of an external chelating Lewis acid (entries 6, 10, 12). In certain cases, however, acyclic auxiliaries may also be useful (see entry 15). 

The lactone concept is not restricted to the simple model biaryl synthesis presented here. It has been successfully expanded to a broad series of structurally diverse biaryl substrates (e.g., lactones with additional stereocenters and functional groups, configurationally stable lactones, seven-membered lactones, and again configurationally unstable biaryl hydroxy aldehydes ), to different activation modes in the ring-opening step (e.g., use of metallated nucleophiles, carbonyl activation by Lewis acids, (Ti -complexation, etc.), and for various strategies of stereoselection (e.g., external vs. internal asymmetric induction). ... 

This chapter deals mainly with the 1,3-dipolar cycloaddition reactions of three 1,3-dipoles azomethine ylides, nitrile oxides, and nitrones. These three have been relatively well investigated, and examples of external reagent-mediated stereocontrolled cycloadditions of other 1,3-dipoles are quite limited. Both nitrile oxides and nitrones are 1,3-dipoles whose cycloaddition reactions with alkene dipolarophiles produce 2-isoxazolines and isoxazolidines, their dihydro derivatives. These two heterocycles have long been used as intermediates in a variety of synthetic applications because their rich functionality. When subjected to reductive cleavage of the N—O bonds of these heterocycles, for example, important building blocks such as p-hydroxy ketones (aldols), a,p-unsaturated ketones, y-amino alcohols, and so on are produced (7-12). Stereocontrolled and/or enantiocontrolled cycloadditions of nitrones are the most widely developed (6,13). Examples of enantioselective Lewis acid catalyzed 1,3-dipolar cycloadditions are summarized by J0rgensen in Chapter 12 of this book, and will not be discussed further here. 

Control of reaction selectivities with external reagents has been quite difficult. Unsolved problems remaining in the held of nitrile oxide cycloadditions are (a) Nitrile oxide cycloadditions to 1,2-disubstituted alkenes are sluggish, the dipoles undergoing facile dimerization to furoxans in most cases (b) the reactions of nitrile oxides with 1,2-disubstituted alkenes nonregioselective (c) stereo- and regiocontrol of this reaction by use of external reagents are not yet well developed and (d) there are few examples of catalysis by Lewis acids known, as is true for catalyzed enantioselective reactions. 

When the guest used is p-nitrophenylcholine carbonate (PNPCC) the Lewis acid zinc(n) activates the well-positioned carbonyl group in the P PCC Zn-cavitand towards reactions with external nucleophiles. The energy minimized structure of the PNPCC Zn-cavitand complex shows that cation-n interactions and C —O -Zn coordination bond occurs simultaneously. 

---