Face selective reactivity

Further prominent examples for face selective reactivity (but for different reasons) are encountered with sulfanilic acid monohydrate 16 and 4-aminobenzoic acid 7. They do not diazotize on their (010) face with N02 or on the (001) face with NOC1, respectively, where molecules cannot exit due to infinite hydrogen-bonded strings. Conversely, at slopes on (010) of 16 or on (100) of 7, where the hydrogen-bonded amino groups of the strings are freely available, reaction occurs [18, 32, 33]. 

Furanones are a class of chiral dienophiles very reactive in thermal cycloadditions. For example, (5R)-5-(/-menthyloxy)-2-(5H)-furanone (28) underwent Diels Alder reaction with cyclopentadiene (21) with complete re-face-selectivity (Equation 2.10), affording a cycloadduct which was used as a key intermediate in the synthesis of dehydro aspidospermidine [27]. 

The face-selectivity of hydride reductions of the conformationally-rigid ketone series (100) has been examined for pure axial and equatorial isomers with four different R groups, viz. Me, Cl, OMe, and SMe.162 The reactivities show Taft correlations with the inductive effects of the substituents. Only through-bond and -space electrostatic interactions are used to explain the results neither Cieplak nor Anh antiperiplanar effects are invoked. 

Design and synthesis of polycyclic molecules with unusual shape, symmetry, and chemically distinct surfaces resulted in a novel class of heterobowls such as 10 (see Section 14.09.2). Although no utilitarian applications of these compounds have been reported yet, this is perhaps because of their recent discovery, the heterobowls might display many interesting properties, such as selective activity for metal ions, face-selective chemical reactivity, surfactant chemistry, and enzyme mimicry <1997TL4173, 2001JOC6905>. 

While the stereochemical outcome of the reactions with chiral (Z)-vinyl sulfoxides can be simply explained in terms of a reactive conformation, the outcome of reactions with chiral (f.)-vinyl sulfoxides cannot be satisfactorily explained. The latter reactions generally proceed with poorer selectivity and with either opposite or the same 7t-face selectivity compared to their Z counterparts94 95. Investigations with chiral (E)- and (Z)-vinyl (/Ci-sulfoxides 23 and ben-zylamine show, besides a solvent effect, that both reaction types proceed with similar diastereoselectivities. The reaction products are formed irreversibly and the extent of interconversion between the ( )- and (Z)-vinyl sulfoxide isomers is small (l-2%)96. 

In the presence of TiCU, EtAlCh, EtjAlCl or Me2AlCl, cyclopentadietie added smoothly to the acry-loyl sultam (363a) at -130 C and to the less reactive crotonoyl sultam (363b) at -78 C (Scheme 89, Table 21). Adducts (366) were formed with excellent endo as well as ir-face selectivities and obtained pure in good yields after crystallization. 

The versatile functionality pattern of bicyclic MO-acetal-y-lactams (found in conjunction with their ir-face-selective alkylation) can also be applied to Diels-Alder reactions of the corresponding alkenic methoxycarbonyl-activated derivative (427) (Scheme 102). ° Noncatalyzed addition of 2,3-dimethylbu-tadiene to dienophile (427) (60 C, 8 h) proceeded exclusively from the ir-face opposite the isopropyl substituent. The reactivities of the latent immonium and carbonyl groups in adduct (428) were exploit during transformation into [l,3,4)propellane (434). 

In the first AD reactions, the emphasis was on face selectivity and reactivity. As the reaction has to be used in more complex systems, the competition between multiple alkenes can occur within a single substrate. To simplify the discussion within this section, molecules with only one alkene are considered first, followed by polyenes. Within each of these sections, olefins are considered first followed by functionalized alkenes. Tables and figures have been used to summarize the vast number of examples in the literature the survey is not intended to be exhaustive, just illustrative. The preferred site of reaction is indicated for many of these, but it should be remembered that oxidation occurs at more than one site and only the major product is indicated. The reader should consult the original citations for more information. 

One stoichiometric method that avoids the use of an expensive chiral auxiliary and allows for the use of nonpyrophoric bases is based on diketopiperazine chemistry. The use of this system as a chiral auxiliary is associated with a method that was developed for the preparation of the sweetener aspartame. At the same time, we were looking at the alkylation reactions of amino acid derivatives and dipeptides. These studies showed that high degrees of asymmetric induction were not simple, were limited to expensive moieties as the chiral units, and required the use of large amounts of lithium [25,26]. The cyclic system of the diketopiperazine has been used successfully by other investigators [27,28], and we also chose to exploit the face selectivity of this unit. L-Aspartic acid was chosen as the auxiliary unit because it is readily available and cheap. All of the studies were performed with sodium as the counterion because it is a more cost-effective metal at scale. Finally, we concentrated in the use of aldehydes rather than alkyl halides to allow for a general approach and so as not to limit the reaction to reactive alkyl halides. 

We have to distinguish face selectivity for reactivity and face selectivity for the shape of the features. AFM easily detects at the molecular level if certain faces are unreactive. Typical examples are given in the solid-state reactions of Scheme 2.1.4. 

Therefore, many Z-chiral substrates show substandard face selectivity and low reactivity, especially when the Z-substrate is bulky and/or functionalized (Scheme 7) [47]. Epoxidations of some chiral Z-substrates do not follow the empirical rules on stereochemistry. 

In solution the intramolecular coordination of the nucleotide function to the lower a-axial coordination site of the corrin-bound cobalt center of complete corrins occurs with Httle build-up of strain [149]. This allows the (coordinating) nucleotide to steer the reactivity, as well as the face-selectivity, of certain organometalUc reactions involving the corrin-boimd cobalt center [75]. Experiments by Eschenmoser demonstrated that cobal-amins can self-constitute in solution from the Bi2-nucleotide portion and incomplete cobyrinic acid derivatives to show a remarkable kinetic and thermodynamic preference for the specific formation of the B 12-structure, and to a pre-enzymatic origin of the basic structural elements of the complete corrins [149]. 

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