Bases homochiral

Jeon Y-M, Heo J, Mirkin CA. Dynamic interconversion of amorphous microparticles and crys-taUine rods in salen-based homochiral infinite coordination pol3miers. J Am Chem Soc 2007 129 7480-7481. 

Preparation of enantiomerically enriched materials by use of chiral catalysts is also based on differences in transition-state energies. While the reactant is part of a complex or intermediate containing a chiral catalyst, it is in a chiral environment. The intermediates and complexes containing each enantiomeric reactant and a homochiral catalyst are diastereomeric and differ in energy. This energy difference can then control selection between the stereoisomeric products of the reaction. If the reaction creates a new stereogenic center in the reactant molecule, there can be a preference for formation of one enantiomer over the other. 

In recent years, enantioselective variants of the above transannular C-H insertions have been extensively stiidied. The enantiodetermining step involves discrimination between the enantiotopic protons of a meso-epoxide by a homochiral base, typically an organolithium in combination with a chiral diamine ligand, to generate a chiral nonracemic lithiated epoxide (e.g., 26 Scheme 5.8). Hodgson... 

Enantiomers (M)- and (P)-helicenebisquinones [32] 93 have been synthesized by high pressure Diels-Alder reaction of homochiral (+)-(2-p-tolylsulfo-nyl)-l,4-benzoquinone (94) in excess with dienes 95 and 96 prepared from the common precursor 97 (Scheme 5.9). The approach is based on the tandem [4 + 2] cycloaddition/pyrolitic sulfoxide elimination as a general one-pot strategy to enantiomerically enriched polycyclic dihydroquinones. Whereas the formation of (M)-helicene is explained by the endo approach of the arylethene toward the less encumbered face of the quinone, the formation of its enantiomeric (P)-form can be the result of an unfavourable interaction between the OMe group of approaching arylethene and the sulfinyl oxygen of 94. 

Peptoids based on a-chiral aliphatic side chains can form stable helices as well [43]. A crystal of a pentameric peptoid homooligomer composed of homochiral N-(1-cyclohexylethyl)glycine residues was grown by slow evaporation from methanol solution, and its structure determined by X-ray crystallographic methods. In the crystalline state, this pentamer adopts a helical conformation with repeating cis-... 

Interconversion of the two enantiomers is possible only if the molecule is removed from the surface and rotated by 180° around an axis parallel to the substrate surface. In the case of PVBA adsorbed on Ag l 11, hydrogen bonding leads to a preference for homochiral double chains based on head-to-tail N—H—O bonds and a C2 axis relating the two strands of the chains. The chirality of the chain can be recognized in the STM images by the stagger of one strand relative to the other that arises from C—H—O bonds, as shown in Figure 1.3 [6],... 

Another attempt to explain the homochirality of biomolecules is based on autocatalysis. The great advantage of asymmetric catalysis is that the catalyst and the chiral product are identical and thus do not need to be separated (Buschmann et al., 2000). The racemic mixture must have been affected by a weak perturbation in order that autocatalysis, which acts as an amplifier of enantioselectivity, could have led to only one of the two enantiomeric forms. This perturbation could have been due to the slight energy difference of the enantiomers referred to above, or to statistical fluctuations. 

Hoveyda, A. H. Diversity-Based Identification of Efficient Homochiral Organometallic Catalysts for Enantioselective Synthesis. In Handbook of Combinatorial Chemistry, Nicolaou, K. C., Hanko, R., Hartwig, W., Eds. Wiley-VCH Weinheim, Germany, 2002, Vol. 2, pp 991-1016. 

Addition of Lithiated Sulfoxides and Sulfones Nucleophilic addition of lithiated methylaryl sulfoxides (384) to nitrones of various structures proceeds easily and in good yields (622). The reactions are applied to the synthesis of optically active a-substituted and a,a-disubstituted hydroxylamines, to secondary amines (623), and to enantioselective syntheses of alkaloids (624). The preferred approach to (+ )-euphococcinine is based on the use of homochiral 3-sullinyl nitrones (385) (Scheme 2.167). 

Since then, optically active a-aminophosphonates have been obtained by a variety of methods including resolution, asymmetric phosphite additions to imine double bonds and sugar-based nitrones, condensation of optically active ureas with phosphites and aldehydes, catalytic asymmetric hydrogenation, and 1,3-dipolar cycloadditions. These approaches have been discussed in a comprehensive review by Dhawan and Redmore.9 More recent protocols involve electrophilic amination of homochiral dioxane acetals,10 alkylation of homochiral imines derived from pinanone11 and ketopinic acid,12 and alkylation of homochiral, bicyclic phosphonamides.13... 

The enantioselective base-promoted rearrangement of oxiranes was achieved by White-sell and Fehnan in 1980. Various homochiral lithium amides were used for the isomerization of cyclohexene oxide with an enantiomeric excess (ee) up to 36% with the employment of 50 in refluxing THF (Scheme 24). 

As for any desymmetrization of meso compounds, enantioselectivity comes from the ability of a homochiral base to distinguish between two enantiotopic protons, in this particular case, to discriminate between the two pseudo-axial protons of the rapidly equilibrating enantiomeric half-chair conformations 51 and 52 (Scheme 25). 

Although modest, the results obtained with nonracemic lithium dialkylamides demonstrated the feasibility of such enantioselective transformations and important work has been undertaken from this date to improve both the yield and the ee values as well as developing a catalytic process. With this objective, both the use of homochiral lithium amide (HCLA) bases and organolithium-homochiral ligand complexes have been explored. This field has been extensively reviewed " and the following section presents a selection of the most outstanding results and recent developments. 

To conclude, the models proposed below are in good agreement with the empirical data and allow a first approach to an efficient rational design of homochiral bases. However, they only take the major NMR or X-ray observable solution HCLA complexes into consideration minor aggregates involving allylic alcoholate or protonated amine products, that might be reactive and contribute to the product formation, are ignored ... 

The first study was performed by Milne and Murphy, who found that the rearrangement of substituted cyclopentene oxide 69 into 70 by a stoichiometric amount of the dilithiated homochiral base 71 derived from norephedrine occurred in excellent yield and good ee... 

This result and the availability of homochiral base 71 in both enantiomeric forms has made this procedure particularly interesting. It has then been successfully applied to the rearrangement of unprotected oxirane 72a into 73a, with excellent stereoselectivity (95% ee Scheme 31) . ... 

While homochiral base 74 promotes asymmetric deprotonation of various oxiranes with an interesting level of enantioselectivity, it appears surprisingly unreactive, as illustrated... 

The RLi homochiral ligand complexes are seldom used for the base-promoted isomerization of oxiranes into allylic alcohols because their poor chemoselectivity lead to complex mixtures of products. As examples, the treatment of cyclohexene oxide by a 1 1 i-BuLi/(—)-sparteine mixture in ether at low temperature provides a mixture of three different products arising respectively from -deprotonation (75), a-deprotonation (76) and nucleophilic addition (77) (Scheme 32) . When exposed to similar conditions, the disubstituted cyclooctene oxide 78 affords a nearly 1 1 mixture of a- and -deprotonation products (79 and 80) with moderate ee (Scheme 32, entry 1). Further studies have demonstrated that the a//3 ratio depends strongly on the type of ligand used (Scheme 32, entry 1 vs. entry 2) . ... 

The only known example of such a catalytic process was reported in 1998 for enan-tioselective arylation of both linear and small ring cis oxiranes. The oxirane is added to a precomplexed mixture of phenylithium (1.6 equivalents) and a homochiral Schiff base of type 107 or 108 (5 mol%) to afford the S,R) ring opening product in moderate to excellent yield with ee s up to 90% (Scheme 48) . 

The use of a catalytic amount of the homochiral ligand is here allowed by the poor reactivity of aryllithium reagents toward oxiranes, the reaction being supposed to occur through the more reactive organolithium/Schiff base complex 109, as depicted in Scheme 49. 

Procedures for synthesis of chiral amines163 164 and halides165 166 167 based on chiral alkylbor-anes have been developed by applying the methods discussed earlier to the homochiral organoborane intermediates. For example, enantiomerically pure terpenes can be converted to trialkylboranes and then aminated with hydroxylaminesulfonic acid. 

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