Initiating chiral element

Structure goal strategies. Identify a potential starting material, building block, retrosynthetic subunit, or initiating chiral element (.see the chiral template approach in sec. 10.9). 

Synthesis of Planar Chiral Aromatic Compounds The Dotz benzannulation reaction initially affords arene complexes, which are somewhat unstable and difficult to isolate. These complexes possess a chirality element that is lost upon decomplexation. The instability originates with the free phenol group, and a relatively stable complex that can easily be isolated using standard organic chemistry techniques is obtained if the free phenol is converted to an ester or silyl ether prior to isolation. Planar chiral arene/transition metal complexes have been used extensively for asymmetric synthesis [27]. 

The retrosynthetic analysis presented in Scheme 6 (for 1, 2, and 16-19) focuses on these symmetry elements, and leads to the design of a strategy that utilizes the readily available enantiomers of xylose and tartaric acid as starting materials and/or chiral auxiliaries to secure optically active materials.14 Thus by following the indicated disconnections in Scheme 6, the initially generated key intermediates 16-19 can be traced to epoxide 23 (16,19 =>23),... 

The remarkable reactivity of borane toward carboxylic acids over esters is one of the conspicuous characteristics of this element, which is rarely seen in any other hydride reagent. An acyloxyborane is recognized as an initial intermediate, hence it became of interest to evaluate the asymmetric induction ability of appropriate chiral auxiliaries by introducing them into such... 

Fluctuations are inherent to any experimental chemical system. Even if these fluctuations are infinitesimally small, they are sufficient to drive the system away from an unstable state. The optically active state is characterized by two equivalent options starting from an unstable racemic situation, the system can evolve into either an R configuration or into an S one. However, each individual experiment remains unpredictable as to which of the optically active states the system will move towards. For a large number of experiments an equal and random distribution between R and S dominance is expected if the initial conditions do not involve any preferences. Due to this unpredictability of the chiral configuration, the phenomenon of mirror-symmetry breaking introduces another element of stochastic behavior into chemical reactions different from that occurring in clock reactions [38,39]. 

The rac-isomers have a twofold axis and therefore C2 symmetry. The meso-iso-mer has a mirror plane as the symmetry element and therefore Cs-symmetry. The racemic mixture can be used for polymerization reactions since the two chains produced by the two enantiomers are identical, if begin and end groups are not considered. The asymmetry possibly introduced initially in the crystal during crystal growth from a chiral catalyst will be removed by melting and crystallization. Note when catalysts of this type are to be used for asymmetric synthesis, e.g. as Lewis acids in Diels-Alder reactions, separation of the enantiomers is a prerequisite. 

Most commonly used chiral Lewis acids have been derived from main group and early transition series elements. An initial attempt at utilizing optically active catalysts of late transition metal complexes for the enantioselective addition of allyltributylstannane to aldehydes was made by Nuss and Rennels [30]. Employment of Rh(COD)[(-)-DIOP]BF4 (11) as a catalyst, however, resulted in only a small degree of asymmetric induction (17% ee). 

Tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) ligands synthesized from tartaric acid have been extensively employed by Narasaka as the chiral control element in selective Diels-Alder reactions. Initial experiments were conducted with simple dienes and a,P-unsaturated imides using complex 44 (Scheme 36) [104,105]. Several rather subtle features have contributed to the success of these endeavors 1) the use of the acetophenone-derived dioxolane rather than the ac-etonide resulted in an increase of 20% ee 2) the use of alkyl-substituted benzenes as solvent augmented enantioselectivities relative to more common organic solvents e.g., CH2CI2, THF) [106] 3) use of 4 A molecular sieves was typically required to achieve maximum enantioselectivity. 

Hans Krebs, the discoverer of the cycle, also pondered this question and at one stage came to the conclusion that citrate could not be an intermediate in the cycle. However, in 1948, Alexander ( Sandy ) Ogston provided the explanation, called the three-point attachment proposal, that was to initiate the concept of prochirality. If citrate is represented as a three-dimensional structure, as in Fig. 10-29, then on the assumption that a three-point attachment to a surface in aconitase is necessary for catalysis, it is seen that citrate can only be accommodated in one orientation. The removal of the elements of water can then only occur from one particular half of the symmetric molecule. Thus a combination of the binding site and the pro-chiral citrate is, overall, asymmetric or has handedness. 

---