Absolute configuration alcohols

Absolute configuration (Section 7 5) The three dimensional arrangement of atoms or groups at a chirality center Acetal (Section 17 8) Product of the reaction of an aldehyde or a ketone with two moles of an alcohol according to the equation... 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

The homology between 22 and 21 is obviously very close. After lithium aluminum hydride reduction of the ethoxycarbonyl function in 22, oxidation of the resultant primary alcohol with PCC furnishes aldehyde 34. Subjection of 34 to sequential carbonyl addition, oxidation, and deprotection reactions then provides ketone 21 (31% overall yield from (—)-33). By virtue of its symmetry, the dextrorotatory monobenzyl ether, (/ )-(+)-33, can also be converted to compound 21, with the same absolute configuration as that derived from (S)-(-)-33, by using a synthetic route that differs only slightly from the one already described. 

Rearrangement of sulfoxides 38a, b exhibited the interplay of several conformational factors. Both diastereomers afford predominant axial (trans) alcohol, but with opposite absolute configuration. The (R, R)-diastereomer strongly prefers the exo-transition state, whereas the (R, S)-isomer prefers the endo conformation. Hoffmann interprets these results in terms of an approximately 3-fold preference for the exo-transition state but a 6-fold preference for formation of an axial bond, these effects reinforcing each other in one isomer but opposing each other in the second. 

It was found that the signs of rotation of the recovered a-phenylbutyric acid corresponded to the known absolute configurations of the deuteriated alcohols if and only if the size relationships CH3 > CD 3 and H>D were valid. In the case of (-t-)-(S)-2-propanol-l,l,l-d3 (4), the optical yield was between 0-4 and 0 5% (Horeau et al., 1965), corresponding to A AG value of about 23 cal mol at 25°C. For the primary alcohols, quite analogous results were obtained (Horeau and Nouaille, 1966). 

Thus, the enantiomeric contents in a pair of sulphoxides can be determined by the H NMR chemical shifts in the methine or methylene protons in the two diastereomeric complexes which are stabilized by the hydrogen bond between the hydroxyl and the sulphinyl groups (Scheme 13). Similarly, the enantiomeric purity and absolute configurations of chiral sulphinate ester can be determined by measuring the NMR shifts in the presence of the optically active alcohols. ... 

Natural products are valuable substrates for further transformations, especially if they contain one or more stereogenic centers of defined absolute configuration. One of the most frequently used natural products in this respect is the monoter-pene a-pinene (6/3-43), which has also been restructured using domino processes. Mehta and coworkers [241] have used the alcohols 6/3-44, easily accessible from a-pinene (6/3-43), for a ROM/RCM reaction to give 6/3-45 and 6/3-46, which were... 

A Mitsunobu process simultaneously coupled the enyne acid fragment 4 to /J-lactam 10 and inverted the CIO stereochemistry to the required (S)-configured ester 11 in 93% yield. A deprotection provided alcohol 12, the key /J-lactam-based macrolactonization substrate, which, under conditions similar to those reported by Palomo for intermolecular alcoholysis of /J-lactams (Ojima et al, 1992, 1993 Palomo et al, 1995), provided the desired core macrocycle 13 of PatA 13 (Hesse, 1991 Manhas et al, 1988 Wasserman, 1987). Subsequent Lindlar hydrogenation gave the required E, Z-dienoate. A Stille reaction and final deprotection cleanly provided (-)-PatA that was identical in all respects to the natural product (Romo etal, 1998 Rzasaef al, 1998). This first total synthesis confirmed the relative and absolute configuration of the natural product and paved the way for synthesis of derivatives for probing the mode of action of this natural product. 

Considering an olefinic functionality as a chromophore, the absolute configuration of cyclic allylic alcohols can be determined using a method that involves the conversion of the alcohol to the corresponding benzoate.60 This can also be extended to acyclic alcohols where the conformations are dynamic (see Fig. 117). Interested readers may consult the literature for details.61... 

It is always advisable to examine the complete molecular topology in the neighborhood of the chiral carbon atom and to confirm the results by employing another analytical method before the final assignment. In conclusion, Prelog s rule does predict the steric course of an asymmetric synthesis carried out with a chiral a-keto ester, and the predictions have been found to be correct in most cases. Indeed, this method has been widely used for determining the absolute configuration of secondary alcohols. 

Another method for determining the absolute configurations of secondary alcohols is Horeau s method, which is based on kinetic resolution. As shown in Scheme 1-14, an optically active alcohol reacts with racemic 2-phenylbutanoic anhydride (54), and an optically active 2-phenylbutanoic acid (52) is obtained after hydrolysis of the half-reacted anhydride. 

Acid obtained Absolute configuration from resolution of the alcohol... 

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