Secondary chiral

The screw models of Figure 7.4 are, of course, an abstraction, and real macromolecules are much more complex. In particular, apart from DNA and G-wires, which have sugar-phosphate backbones as external ridges, but are also charged, most natural and synthetic polymers have external side chains which could generate a secondary chiral surface, which might interfere with the chirality of the polymer backbone.28 Even if the qualitative estimate of Sq based on the models of Figure 7.4 seems rather primitive, the estimate of Hq... 

On the basis of their earlier aromatic annulation strategy (see Scheme 5.64) (596), Shin and Ogasawara reported the first enantioselective total synthesis of carbazo-quinocins A (272) and D (275) (639). The required methyl-substituted secondary chiral stereogenic center of the alkyl side chain at C-1 of carbazoquinocins A and D was introduced starting from the O-benzyl (R)-glycidol (R)-897. 

SCHEME 64. Titanium-catalyzed asymmetric epoxidation of aUyhc alcohols with secondary chiral hydroperoxides in the presence of diol additives... 

Scheme 2.25 Mechanism for the catalytic enantioselective a-heteroatom functionalization of aldehydes and ketones catalyzed by secondary chiral amines.

The obvious question is whether the achiral stereodirecting base effect observed with DAG is a particular case of this alcohol or general behavior of secondary chiral carbinols. In order to answer this question and to get a better insight into the mechanism of the reaction, the reactivity of different chiral carbinols with methane-sulfinyl chloride was tested using the optimal conditions previously determined for DAG (1) in the presence of i-Pr2NEt in toluene at -78 °C, and (2) with pyridine in THF at -78 °C.116... 

In the presence of a base, secondary chiral phosphine oxides undergo addition to carbonyl compounds to give a-hydroxy phosphine oxides as diastereomeric mixtures the diastereomer ratio depends mainly on the reaction conditions. For example, the reaction of ethyl(phenyl)-phosphinc oxide with benzophenone in the presence of a catalytic amount of sodium ethoxide gives at 75 =C exclusively while at 25°C the ratio [(P/ , / )-l/(P7 , S )-l] is 7 326. 

The crucial role of the secondary liberated amine was also reported in experiments involving deprotonation with lithium (/ )-A -ethyl(l-phenylethyl)amide and reprotonation at —70°C with 2R,3R, racemic, and meso-DPTA, yielding, respectively, 70, 39, and 24% ee of the (5)-enantiomer. In the two last cases, significant inductions were obtained with the sole secondary chiral amine as chiral inductor in the medium. Since these first results, chiral lithium amides have been widely used for asymmetric synthesis. 

The oxidation of limonene (111) by selenium dioxide has been studied in three laboratories and, using hydroxylated solvents, the major product is mentha-1,8-dien-4-ol (112), in agreement with the results from the selenium dioxide oxidation of carvone (117) where the main product is also the 4-hydroxy-compound (118), also with loss of chirality at C-4. The mechanism giving rise to the secondary chiral products trons-carveol (113) and mentha-l,8-dien-10-ol... 

In the previons section, secondary chiral amines were employed that give rise to enamine formation npon reaction with ketones or aldehydes. Chiral tertiary amines, unable to form enamines, are nevertheless capable of inducing enantioselectivity in case substrates are used that contain sufficiently acidic protons such as aldehydes, ketones or active methylene compounds [33]. The cinchona alkaloids, by far the most versatile source of Brpnsted base catalysts, have played a prominent role in various types of asymmetric organocatalytic reactions [34], which is also true for the Mannich reaction. 

At the initial stage, the Ru catalyst, [Ru(ll)(bpy)3] , is excited by irradiation with a 15 W fluorescent light bulb to form the excited species, [Ru(ll)(bpy)3] , which is reduced by enamine 3 derived from the reaction of the secondary chiral amine catalyst with aldehydes 1 [31, 32]. The resulting strong reductant, [Ru(l) (l py)3], undergoes SET to alkyl halide 2, leading to formation of alkyl radical and... 

In the case of enals, the most common catalysts are secondary chiral amines, which can be divided into two large groups (i) amines substituted with a bulky group and (ii) amines with hydrogen-bond-directing groups. Another possible type of catalyst for this activation mode arises from ACDC (asymmetric counterion direct catalysis) developed by List. In these catalysts either a chiral or non-chiral amine forms a chiral ionic pair with a chiral phosphoric acid. A different possibility is the use of a primary chiral amine and a strong acid. These latter methods have... 

Organocatalysts To date, the main classes of organocatalysts that have been used are [42] imidazolidinone, diarylprolinol silyl ether, cinchona alkaloid, and phosphoric acid and thiourea derivatives. Essentially, two modes of activation can be considered the reversible formation of iminiums/enamines (covalent activation) with a,P-unsaturated aldehydes and ketones in the presence of primary or secondary chiral amines (Figure 35.1), and activation via hydrogen-bond formation (non-covalent activation) when chiral catalysts bearing hydrogen-bond donors are used (Figure 35.2). 

Figure 35.1 Representative primary and secondary chiral amines (iminium-enamine activation).

The process of the diastereoselective formation of 66/68 involves a rhodium-catalyzed C—H activation after precoordination of the metal to the nitrogen of 67 to form the species 70 followed by a iyK-alkene insertion and a reductive elimination. The secondary chiral silylether group should induce the diastereoselective formation of the C (sp ) C(sp ) bond to afford the product with the correct relative configurations (Scheme 23.16). 

Extension of this methodology to the assignment of nonsymmetrical 1,/7-diols with two secondary (chiral) hydroxyl groups, or with primary and secondary (chiral) hydroxyl groups, as well as amino alcohols, has been conducted and shown to be successful. 

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