Equatorial asymmetric syntheses

Another possibility to increase the diastereoselectivity in an asymmetric synthesis can arise from different thermodynamic stabilities of the diasteieoisomeric products. If the thermodynamic stabilities of these are different enough, then, under conditions of equilibrium, a complete conversion of the less stable into the more stable can be achieved. For example, the diastereoselective hydrogenation of naphthalene derivates over Pd/C catalyst leads to a mixture of dihydronaphtalenes in which the cA-isomer predominates. The conversion of this isomer into the tram occurs by changing the properties of the reaction medium, namely by equilibration with a base. For such a purpose, NaOMe in IHF can be used [263], Generally, such an increase in stability in the six-membered rings can result from a rearrangement of the substituents from an axial to an equatorial position. 

In another study (93), cyclization of optically active substrate 244 gave optically active tetracyclic product 245 with the same optical purity. Since, 245 was converted into Ua-hydroxyprogesterone (246), this work constitutes a total asymmetric synthesis of that steroid. This remarkable asymmetric control is due to the chiral center at C-10 of 244 the relative orientation of the hydroxyl group in the transition state of the cyclization process, controlled by stereoelectronic factors, is such that it yields a product (245) having an equatorial secondary alcohol. 

The most popular lands of the diols for asymmetric synthesis are bis-secondary diols that have a C2 axis of symmetry [212]. The presence of the symmetry axis avoids the formation of diastereoisomeric esters or acetals [213], (1R, 27 )-Cyclohexanediol 1.34 (n = 1) has been used as an auxiliary in asymmetric cyclopropanation [214] and (IS, 2S)-cycloheptanediol 1.34 (n = 2) in 1,4-addition of cuprates[157], Dioxolane derivatives of 1.34 have been used for asymmetric P-ketoester alkylations [215] and cuprate 1,4-additions [216]. Linear 1,2-diols 1.35 (R = Me, i-Pr, c-CgH j, Ph) and functionalized 1,2-diols 1.36 (Y = COOalkyl, CONR 2, CH2OR ) are readily available from optically active tartaric acids 1.36 (Y = COOH). Acetals derived from these diols are valuable reagents m asymmetric synthesis [173, 213, 217], as the related 1,3-diols 1.37. Acetals of 1,3-butanediol 137 (R = Me, R = H) have also been used. When these acetals are formed from aldehydes under thermodynamic conditions, one 1,3-di-oxane stereoisomer often predominates. In this favored isomer, the substituent from the aldehyde and the methyl group from 1.37 are both in equatorial orientar... 

As an analog, 1,3,5-trithiane 1-tosylimide 154 was synthesized by the reaction between chloroamine-T and 1,3,5-trithiane in DMF. After pouring the reaction solution into cold water, the precipitate, recrystallized from acetonitrile, was proven by X-ray crystallography to have the tosylimino group equatorially oriented on a 1,3,5-trithiane chair conformer (Scheme 40) <1994J(P2)1439>. The sodium salt 156 reacted further with NaH/Mel in dimethylformamide (DMF) but delivered a product mixture of ( )-155 and meso-155. Thus the authors failed to break the symmetry of 154 and, as part of their asymmetric synthesis program, to deliver enantiomerically enriched products (Scheme 40) <1995J(P1)313>. 

Asymmetric induction (See also Enantioselective) chiral ketones, 62, 106-107 chiral sulfoxides, 8-9 steroid synthesis, 27, 278-281 Asymmetric syntheses. See Enantioselective. .. Asymmetry of vesicle membranes, 351 dATP. See 2 -Deoxynucleoside 5 -triphosphates Atropisomers binap chelands, 102-103 Kemp s acid arylimides, 347 porphyrin oligomers, 348—349 5,10,15,20-tetraarylporphyrins, 253 Axial/equatorial stereoselectivity ... 

Stereoselectivity. See Asymmetric induction Axial/equatorial-, Cis/trans-, Enantio-, Endo/exo- or Erythro/threo-Selectivity Inversion Retention definition (e.e.), 107 footnote Steric hindrance, overcoming of in acylations, 145 in aldol type reactions, 55-56 in corrin synthesis, 261-262 in Diels-Alder cyclizations, 86 in Michael type additions, 90 in oiefinations Barton olefination, 34-35 McMurry olefination, 41 Peterson olefination, 33 in syntheses of ce-hydrdoxy ketones, 52 Steric strain, due to bridges (Bredt s rule) effect on enolization, 276, 277, 296, 299 effect on f3-lactam stability, 311-315 —, due to crowding, release of in chlorophyll synthesis, 258-259 in metc-cyclophane rearrangement, 38, 338 in dodecahedrane synthesis, 336-337 in prismane synthesis, 330 in tetrahedrane synthesis, 330 —, due to small angles, release of, 79-80, 330-333, 337... 

---