Facial selection

The regioselectivity benefits from the increased polarisation of the alkene moiety, reflected in the increased difference in the orbital coefficients on carbon 1 and 2. The increase in endo-exo selectivity is a result of an increased secondary orbital interaction that can be attributed to the increased orbital coefficient on the carbonyl carbon ". Also increased dipolar interactions, as a result of an increased polarisation, will contribute. Interestingly, Yamamoto has demonstrated that by usirg a very bulky catalyst the endo-pathway can be blocked and an excess of exo product can be obtained The increased di as tereo facial selectivity has been attributed to a more compact transition state for the catalysed reaction as a result of more efficient primary and secondary orbital interactions as well as conformational changes in the complexed dienophile" . Calculations show that, with the polarisation of the dienophile, the extent of asynchronicity in the activated complex increases . Some authors even report a zwitteriorric character of the activated complex of the Lewis-acid catalysed reaction " . Currently, Lewis-acid catalysis of Diels-Alder reactions is everyday practice in synthetic organic chemistry. 

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 second C-C bond forming step (step C), while occurring after the first irreversible ee determining step (step B), can affect the observed enantioselective outcome of the reaction. If the radical intermediate collapses without rotation (k3 Ict, k5 ke), then the observed ee would be determined by the first C-C bond forming step (ki vs. k2), that is the facial selectivity (Scheme 1.4.6). However, if rotation is allowed followed by collapse, then the rate of both trans pathways (Ic and k ) will proportionally effect the observed ee of the cis epoxide (ks vs. ks). Should bond rotation be permissible, the diastereomeric nature of the radical intermediates 9a and 9b renders the distinct possibility of different observed ee s for frany-epoxides and dy-epoxides. 

The addition followed a radical chain mechanism initiated by photoinitiated electron transfer from the tertiary amine to the excited aromatic ketone and occurred with complete facial selectivity on the furanone ring (99TL3169). The yields increased and best results were obtained with sensitizers (4-methoxyacetophenone,... 

With 2,3-[isopropylidenebis(oxy)]propanal the facial selectivity of the allylstannane generated from tin(II) chloride, the disodium salt of diethyl 2,3-dihydroxybutanoatc, and 3-bromo-1-propene (see preceding section) is overwhelmed by the facial selectivity of the substrate97. Some selectivity was observed in coupling monosaccharide derived allylstannanes with monosaccharide aldehydes99. 

A certain jr-facial selectivity was achieved when MCpCl2 (M = Ti, Zr) fragments were coordinated to the optically active fused cyclopentadienyl ligands. For instance, reaction of ZrCpCl3 with the lithium derivative of 126 at —78 °C gave predominantly 133 which was characterized by X-ray structural analysis [152]. 

Asymmetric versions of the cyclopropanation reaction of electron-deficient olefins using chirally modified Fischer carbene complexes, prepared by exchange of CO ligands with chiral bisphosphites [21a] or phosphines [21b], have been tested. However, the asymmetric inductions are rather modest [21a] or not quantified (only the observation that the cyclopropane is optically active is reported) [21b]. Much better facial selectivities are reached in the cyclopropanation of enantiopure alkenyl oxazolines with aryl- or alkyl-substituted alkoxy-carbene complexes of chromium [22] (Scheme 5). 

An asymmetric version of this reaction was achieved by the use of complexes derived from chiral imidazolidinones. For example, the reaction of Danishefsky s diene with these chiral complexes occurs with both high exo endo selectivity and high facial selectivity at the dienophile [103] (Scheme 56). 

The cycloaddition of chiral, racemic and non-racemic alkoxybutadienes 109 with phenyltriazolinedione led to aza compounds [110] in high yield, with good facial selectivity (diastereomeric excess 87-92%) (Equation 2.31). The cycloadditions of the same dienes with N-phenylmaleimide require Lewis acid catalysis. 

An interesting phenomenon has been observed in the high pressure Diels-Alder reactions of the l-oxa[4.4.4]propella-5,7-diene (117) with 1,4-naphthoquinone, maleic anhydride and N-phenylmaleimide, where the diene 117 undergoes a rearrangement to the diene isomer 118 which, although thermodynamically less favored, exhibits a greater reactivity [40]. The reactivities of the three dienophiles differed since maleic anhydride and N-phenylmaleimide reacted only in the presence of diisopropylethylamine (DIEA) and camphorsulfonic acid (CSA), respectively (Scheme 5.15). The distribution of the adduct pairs shows that the oxygen atom does not exert a consistent oriental dominance on TT-facial selectivity. 

Most of the time, the addition is predominantly endo that is, the more bulk) side of the alkene is under the ring, and this is probably true for open-chain dienes also. However, exceptions are known, and in many cases mixtures of exo and endo addition products are found. It has been argued that facial selectivity is not due to torsional angle decompression. ... 

The orbital mixing rules are described in detail and shown to be powerful for understanding and designing selective reactions in Chapter Orbital Mixing Rules and applied in chapter ji-Facial Selectivities of Diels-Alder reactions . 

Keywords Orbital mixing. Orbital amplitude. Orbital phase. Orbital polarization. Orbital deformation, Regioselectivity, Stereoselectivity, n Facial selectivity... 

The orbital mixing theory was developed by Inagaki and Fukui [1] to predict the direction of nonequivalent orbital extension of plane-asymmetric olefins and to understand the n facial selectivity. The orbital mixing rules were successfully apphed to understand diverse chemical phenomena [2] and to design n facial selective Diels-Alder reactions [28-34], The applications to the n facial selectivities of Diels-Alder reactions are reviewed by Ishida and Inagaki elesewhere in this volume. Ohwada [26, 27, 35, 36] proposed that the orbital phase relation between the reaction sites and the groups in their environment could control the n facial selectivities and review the orbital phase environments and the selectivities elsewhere in this volume. Here, we review applications of the orbital mixing rules to the n facial selectivities of reactions other than the Diels-Alder reactions. 

Scheme 34 Opposite n facial selectivities of the photooxidations of the 7-methyenenorbomene and bicylo[2.2.2]octadiene derivatives...

Fukui [51] predicted the deformation of the LUMO of cyclohexanone by the orbital mixing rule [1,2] and explained the origin of the % facial selectivity of the reduction of cyclohexanone. Tomoda and Senju [52] calculated the LUMO densities on the... 

Keywords Facial selection. Orbital phase, Secondary orbital interaction. Orbital unsymmetrization. Ketones, Olefins, Diels-Alder dienophiles, Diels-Alder dienes, Michael acceptor. Amine nitrogen atom... 

Steric repulsions come from two orbital-four electron interactions between two occupied orbitals. Facially selective reactions do occur in sterically unbiased systems, and these facial selectivities can be interpreted in terms of unsymmetrical K faces. Particular emphasis has been placed on the dissymmetrization of the orbital extension, i.e., orbital distortions [1, 2]. The orbital distortions are described in (Chapter Orbital Mixing Rules by Inagaki in this volume). Here, we review the effects of unsymmetrization of the orbitals due to phase environment in the vicinity of the reaction centers [3]. 

Deformation of symmetrical orbital extension of carbonyl or olefin compounds was proposed to be the origin of the facial selectivities. We illustrate the unsymmetrical orbital phase environment of % orbitals of carbonyl and olefin groups and facial selectivities in Fig. 1 [3, 4]. There are in-phase and out-of-phase combinations of... 

In this review we will focus on the unsymmetrization of the orbital phase environment in the vicinity of reacting n systems, and its effect on facial selectivities. This idea can be applied to many kinds of recently observed facial selectivities, such as those involving ketones [10-21], olefins [22-31], dienes [32-46] and others [47-49]. 

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