Optically active internal

T.F. Walsh and co-workers synthesized two (S)- 3-methyl-2-aryltryptamine based gonadotropin hormone antagonists via a consecutive Larock indole synthesis and Suzuki cross-coupling. The required (S)-P-methyltryptophol derivatives were prepared by coupling 4-substituted o-iodoanilines with optically active internal alkynes under standard conditions. The resulting 2-trialkylsilyl substituted indoles were then subjected to a silver-assisted iododesilylation reaction to afford the 2-iodo-substituted indoles that served as coupling partners for the Suzuki cross-coupling step. 

Shiner, C. S., Gamer, C. M., Haltiwanger, R. C. (1985). Synthesis and crystal structure of an optically active, internally coordinated alkylchloroborane. The boron-centered anomeric effect. Journal of the American Chemical Society, 107, 7167-7172. 

Multiple Chiral Centers. The number of stereoisomers increases rapidly with an increase in the number of chiral centers in a molecule. A molecule possessing two chiral atoms should have four optical isomers, that is, four structures consisting of two pairs of enantiomers. However, if a compound has two chiral centers but both centers have the same four substituents attached, the total number of isomers is three rather than four. One isomer of such a compound is not chiral because it is identical with its mirror image it has an internal mirror plane. This is an example of a diaster-eomer. The achiral structure is denoted as a meso compound. Diastereomers have different physical and chemical properties from the optically active enantiomers. Recognition of a plane of symmetry is usually the easiest way to detect a meso compound. The stereoisomers of tartaric acid are examples of compounds with multiple chiral centers (see Fig. 1.14), and one of its isomers is a meso compound. 

M-Acyliminium cyclizations of optically active mono- and di-oxygenated hydroxylactam derivatives have been used in the synthesis of a number of natural products. In case of a five-membered lactam the oxygen function adjacent to the iminium carbon directs attack of the internal nucleophile from the least hindered side, opposite to the substituent. In the examples given the size of the newly formed ring is determined by the electronic bias of the alkene substituent. 

Analogous results were obtained for enol ether bromination. The reaction of ring-substituted a-methoxy-styrenes (ref. 12) and ethoxyvinylethers (ref. 10), for example, leads to solvent-incorporated products in which only methanol attacks the carbon atom bearing the ether substituent. A nice application of these high regio-and chemoselectivities is found in the synthesis of optically active 2-alkylalkanoic acids (ref. 13). The key step of this asymmetric synthesis is the regioselective and chemoselective bromination of the enol ether 4 in which the chiral inductor is tartaric acid, one of the alcohol functions of which acts as an internal nucleophile (eqn. 2). 

We have previously discussed the possibilities of racemization or inversion of the product RS of a solvolysis reaction. However, the formation of an ion pair followed by internal return can also affect the stereochemistry of the substrate molecule RX. Cases have been found where internal return racemizes an original optically active RX, an example being solvolysis in aqueous acetone of a-p-anisylethyl p-nitrobenzoate, while in other cases partial or complete retention is found, for example, solvolysis in aqueous acetone of p-chloro benzhydryl p-nitrobenzoate. the pathway RX R+X some cases where internal return involves racemization, it has been shown that such racemization is faster than solvolysis. For example, optically active p-chlorobenzhydryl chloride racemizes 30 times faster than it solvolyzes in acetic acid. ... 

To date, direct asymmetric synthesis of optically active chiral-at-metal complexes, which by definition leads to a mixture of enantiomers in unequal amounts thanks to an external chiral auxiUary, has never been achieved. The most studied strategy is currently indirect asymmetric synthesis, which involves (i) the stereoselective formation of the chiral-at-metal complex thanks to a chiral inductor located either on the ligand or on the counterion and then (ii) removal of this internal chiral auxiliary (Fig. 4). Indeed, when the isomerization of the stereogenic metal center is possible in solution, in-... 

Akiyama, T. Magara, K. Matsumoto, Y. Ishizu, A. Meshitsuka, G. Lundquist, K. Studies on the optical activities of arylglycerol-P-aryl ether structures in lignin. In 11th International Symposium of Wood and Pulping Chemistry, Nice, France, Association Technique de TIndustrie Papeti ere (ATIP), Paris 2001 Vol. Ill, pp 537-540. 

Linear Tetrasilanes with Internal Substituents Oligosilanes with Optical Activity... 

Breuer, M., Ditrich, K., Habicher, T. et al. (2004) Industrial methods for the production of optically active intermediates. Angewandte Chemie-International Edition, 43 (7), 788-824. 

In comparison with the platinum catalysts, rhodium catalysts are much more reactive to effect addition of bis(catecholato)diboron even to non-strained internal alkenes under mild reaction conditions (Equation (5)).53-55 This higher reactivity prompted trials on the asymmetric diboration of alkenes. Diastereoselective addition of optically active diboron derived from (li ,2i )-diphenylethanediol for />-methoxystyrene gives 60% de (Equation (6)).50 Furthermore, enantioselective diboration of alkenes with bis(catecolato)diboron has been achieved by using Rh(nbd)(acac)/(A)-QUINAP catalyst (Equation (7)).55,56 The reaction of internal (A)-alkenes with / //-butylethylene derivatives gives high enantioselectivities (up to 98% ee), whereas lower ee s are obtained in the reaction of internal (Z)-alkenes, styrene, and a-methylstyrene. 

Noyori et al. (17) applied this catalyst to the asymmetric cyclopropanation of al-lenes and found that carbenoid transfer occurred selectively to the internal alkene, Eq. 4 (17). The product cyclopropanes 9 and 10 were formed in optically active form but the ee could not be determined, a reflection of the lack of analytical techniques available at the time. 

Several other types of photochemical reactions involving unsaturated carbohydrates have been reported. One of these is38 photochemical, E -Z isomerization of the groups attached to a double bond (see Scheme 5). A second is the internal cycloaddition between two double bonds connected by a carbohydrate chain.39-41 Although the carbohydrate portion of the molecule is not directly involved in this cycloaddition, its presence induces optical activity in the cyclobutane derivatives produced photochemically. Finally, a group of acid-catalyzed addition-reactions has been observed for which the catalyst appears to arise from photochemical decomposition of a noncarbohydrate reactant.42-44... 

Most optically active polysilanes owe their optical activity to induced main-chain chirality, as outlined above. However, backbone silicon atoms with two different side-chain substituents are chiral. Long-chain catenates, however, are effectively internally racemized by the random stereochemistry at silicon, and inherent main-chain chirality is not observed. For oligosilanes, however, inherent main-chain chirality has been demonstrated. A series of 2,3-disubstituted tetrasilanes, H3Si[Si(H)X]2SiH3 (where X = Ph, Cl, or Br), were obtained from octaphenylcyclote-trasilane and contain two chiral main-chain silicon atoms, 6.16 These give rise to four diastereoisomers the optically active S,S and R,R forms, the activity of which is equal but opposite, resulting in a racemic (and consequently optically inactive) mixture and the two meso-forms, S,R and R,S, which are optically inactive by internal compensation. It is reported that the diastereoisomers could be distinguished in NMR and GC/MS experiments. For the case of 2-phenyltetrasilane, a racemic mixture of (R)- and (A)-enantiomers was obtained. 

We have already seen that mesotartaric acid is optically inactive because of internal compensation, although, it contains two asymmetric carbon atoms. We have also seen that the molecule as a whole must be asymmetric for being optically active. Therefore, the best criterion to judge optical activity would be whether molecule is superimposable on its mirror image or not. Now superimposability would lead to optical activity and vice-versa and non-symmetrical molecules are non superimposable. To decide whether a molecule is symmetrical or not, we should first try to know whether it has a plane of symmetry, a centre of symmetry or an alternating axis of symmetry. The presence of any one of these would lead the molecule to be symmetrical and hence to optical inactivity. 

Therefore, an optically active substance is one that rotates the plane of polarized light. In other words, certain specific substances by virtue of their internal structure may be able to transmit only such vibrations that are oriented along certain directions and entirely block vibrations in other directions. 

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