Optical activity preparation

Seehach D, Boes M, Naef R, Saweizer WB. Alkylation of amino acids without loss of the optical activity preparation of a-substituted proUne derivatives. A case of selfreproduction of chirahty. 7. Am. Chem. Soc. 1983 105 5390 5398. 

Borneol and isoboineol are respectively the endo and exo forms of the alcohol. Borneol can be prepared by reduction of camphor inactive borneol is also obtained by the acid hydration of pinene or camphene. Borneol has a smell like camphor. The m.p. of the optically active forms is 208-5 C but the racemic form has m.p. 210-5 C. Oxidized to camphor, dehydrated to camphene. 

HC CH(0H) CH20H. optically active. D-glyceraldehyde is a colourless syrup. May be prepared by mild oxidation of glycerol or by hydrolysis of glyceraldehyde acetal (prepared by oxidation of acrolein acetol). DL-glyceraldehyde forms colourless dimers, m.p. IBS-S C. Converted to methylglyoxal by warm dilute sulphuric acid. The enantiomers... 

C3H6O4, HO OCHCOHj-CH OH. An un-crystallizable syrup it occurs in optically active forms. Prepared by oxidation of glycerin with nitric acid. 

Isovaleric acid, Me2CHCH2COOH, is a colourless liquid with the unpleasant odour of valerian, b.p. 177 "C. Occurs in the roots of valerian and angelica together with an optically active form of methylethylethanoic acid. Prepared by oxidation of isoamyl alcohol. A mixture of acids similar to that obtained from valerian roots is prepared by oxidation of fusel oil. 

Acetophenone similarly gives an oxime, CHjCCgHjlCtNOH, of m.p. 59° owing to its lower m.p. and its greater solubility in most liquids, it is not as suitable as the phenylhydrazone for characterising the ketone. Its chief use is for the preparation of 1-phenyl-ethylamine, CHjCCgHslCHNHj, which can be readily obtained by the reduction of the oxime or by the Leuckart reaction (p. 223), and which can then be resolved by d-tartaric acid and /-malic acid into optically active forms. The optically active amine is frequently used in turn for the resolution of racemic acids. 

The asymmetric cyclopalladation of dimethylaminomethylferrocene takes place in the presence of an optically active carboxylic acid (e.g, A -acetylvaline), giving the cyclopalladation product 478 in 78% ee, from which optically active ferrocene derivatives were prepared[434]. 

The carbonyiation of o-diiodobenzene with a primary amine affords the phthalimide 501 [355,356]. Carbonyiation of iodobenzene in the presence of (9-diaminobenzene (502) and DBU or 2,6-lutidine affords 2-phenylbenzimida-zole (503)[357, The carbonyiation of aryl iodides in the presence of pentaflnor-oaniline affords 2-arylbenzoxazoles directly, 2-Arylbenzoxazole is prepared indirectly by the carbonyiation of (9-aminophenol[358j. The optically active aryl or alkenyl oxazolinc 505 is prepared by the carbonyiation of the aryl or enol triflates in the presence of the opticaly active amino alcohol 504, followed by treatment with thionyl chloride[359]. 

Organophosphorus compounds. Phosphorus-carbon bond fonnation takes place by the reaction of various phosphorus compounds containing a P—H bond with halides or tritlates. Alkylaryl- or alkenylalkylphosphinates are prepared from alkylphosphinate[638]. The optically active isopropyl alkenyl-methylphosphinate 778 is prepared from isopropyl methylphosphinate with retention[639]. The monoaryl and symmetrical and asymmetric diarylphosphi-nates 780, 781, and 782 are prepared by the reaction of the unstable methyl phosphinate 779 with different amounts of aryl iodides. Tnmethyl orthoformate is added to stabilize the methyl phosphinate[640]. 

Phosphine oxides are prepared similarly[644]. Selective monophosphiny-lation of 2,2 -bis[(lrifluoromethanesulfonyl)oxy]-l,1 -binaphthyl (784) with diphenylphosphine oxide using dppb or dppp as a ligand takes place to give optically active 2-(diarylphosphino)-1,1 -binaphthyl (785). No bis-substitution is observed[645,646]. 

The optically active 1,4-cyclohexenediol monoacetate 525, prepared by hydrolysis of the me.so-diacetate with lipase, was converted into the optically pure cyclohexenone 526 by an elimination reaction in the presence of ammonium formate. Optically active carvone (527) was prepared from 526[343],... 

Diisocyanobenzene (130) undergoes living polymerization to form the poly(quinoxaline-2,3-diyl)s 131, and the optically active helical polyfquinoxa-line-2,3-diyl) 132 is prepared from 131[123]. 

Phosphorus is m the same group of the periodic table as nitrogen and tricoordi nate phosphorus compounds (phosphines) like amines are trigonal pyramidal Phos phmes however undergo pyramidal inversion much more slowly than amines and a number of optically active phosphines have been prepared... 

An advantage that sulfonate esters have over alkyl halides is that their prepara tion from alcohols does not involve any of the bonds to carbon The alcohol oxygen becomes the oxygen that connects the alkyl group to the sulfonyl group Thus the configuration of a sulfonate ester is exactly the same as that of the alcohol from which It was prepared If we wish to study the stereochemistry of nucleophilic substitution m an optically active substrate for example we know that a tosylate ester will have the same configuration and the same optical purity as the alcohol from which it was prepared... 

The few studies that have been carried out with optically active tertiary alcohols indicate that almost complete racemization accompanies the preparation of tertiary alkyl halides by this method... 

Other uses of Snp2 are in the synthesis of fluorophosphate glasses having low melting temperatures (13—15), in formation of transparent film (16), and in the preparation of optically active alcohols (17). 

Pubhcations have described the use of HFPO to prepare acyl fluorides (53), fluoroketones (54), fluorinated heterocycles (55), as well as serving as a source of difluorocarbene for the synthesis of numerous cycHc and acycHc compounds (56). The isomerization of HFPO to hexafluoroacetone by hydrogen fluoride has been used as part of a one-pot synthesis of bisphenol AF (57). HFPO has been used as the starting material for the preparation of optically active perfluorinated acids (58). The nmr spectmm of HFPO is given in Reference 59. The molecular stmcture of HFPO has been deterrnined by gas-phase electron diffraction (13). 

Synthetic utility of stereoselective alkylations in natural product chemistry is exemplified by the preparation of optically active 2-arylglycine esters (38). Chirally specific a-amino acids with methoxyaryl groups attached to the a-carbon were prepared by reaction of the dimethyl ether of a chiral bis-lactam derivative with methoxy arenes. Using SnCl as the Lewis acid, enantioselectivities ranging from 65 to 95% were obtained. 

Optically active 2-arylalkanoic acid esters have been prepared by the Friedel-Crafts alkylation of arenes with optically active a-sulfonyloxy esters (40). Friedel-Crafts alkylation of ben2ene with (5)-methyl 2-(chlorosulfonyloxy)- or 2-(mesyloxy)propionate proceeded with predorninant inversion of configuration (<97%) to give (5)-methyl 2-phenylpropionate. 

In view of the ready availabiUty of optically pure lactic acid derivatives this reaction offers an attractive general method for the preparation of optically pure aromatic ester derivatives (41). Stereoselective alkylation (15—60% inversion) of ben2ene with optically active 1,2- 1,3- and 1,5-dihaloalkanes was also reported (42). 

Secondary amines having one oi two chiral groups attached to the nitrogen atom are prepared from boronic esters by their conversion into alkyldichlotobotanes, followed by treatment with organic azides (518). The second chiral group can be derived from an optically active azide. 

Optically Active PO. The synthesis of optically pure PO has been accompHshed by microbial asymmetric reduction of chloroacetone [78-95-5] (90). (3)-2-Meth5loxirane [16088-62-3] (PO) can be prepared in 90% optical purity from ethyl (3)-lactate in 44% overall yield (91). This method gives good optical purity from inexpensive reagents without the need for chromatography or a fermentation step. (3)-PO is available from Aldrich Chemical Company, having a specific rotation [0 ] ° 7.2 (c = 1, CHCl ). 

High yields of optically active cyanohydrins have been prepared from hydrogen cyanide and carbonyl compounds using an enzyme as catalyst. Reduction of these optically active cyanohydrins with lithium aluminum hydride in ether affords the corresponding substituted, optically active ethanolamine (5) (see Alkanolamines). 

Lipase-catalyzed kinetic resolutions are often practical for the preparation of optically active pharmaceuticals (61). For example, suprofen [40828-46-4] (45), which is a nonsteroidal antiinflamatory dmg, can be resolved by Candida glindracea]i 2Lse in >95% ee at 49% conversion (61). Moreover, hpase-based processes for the resolution of naproxen [22204-53-1] and ibuprofen [15687-27-1] (61) have also been developed. 

Optically active 2-arylaIkanoic acid esters have been prepared by Eriedel-Crafts alkylation of arenes with optically active esters, such as methyl 3 -2-(chlorosulfonoxy)- or 3 -2-(mesyloxy)propionate, in the presence of aluminum chloride (54,55). 

The synthesis of dextromethorphan is an outgrowth of early efforts to synthesize the morphine skeleton. /V-Methy1morphinan(40) was synthesized in 1946 (58,59). The 3-hydroxyl and the 3-methoxy analogues were prepared by the same method. Whereas the natural alkaloids of opium are optically active, ie, only one optical isomer can be isolated, synthetic routes to the morphine skeleton provide racemic mixtures, ie, both optical isomers, which can be separated, tested, and compared pharmacologically. In the case of 3-methoxy-/V-methylmorphinan, the levorotatory isomer levorphanol [77-07-6] (levorphan) was found to possess both analgesic and antitussive activity whereas the dextrorotatory isomer, dextromethorphan (39), possessed only antitussive activity. Dextromethorphan, unlike most narcotics, does not depress ciUary activity, secretion of respiratory tract fluid, or respiration. 

Also due to the high barrier of inversion, optically active oxaziridines are stable and were prepared repeatedly. To avoid additional centres of asymmetry in the molecule, symmetrical ketones were used as starting materials and converted to oxaziridines by optically active peroxyacids via their ketimines (69CC1086, 69JCS(C)2648). In optically active oxaziridines, made from benzophenone, cyclohexanone and adamantanone, the order of magnitude of the inversion barriers was determined by racemization experiments and was found to be identical with former results of NMR study. Inversion barriers of 128-132 kJ moF were found in the A-isopropyl compounds of the ketones mentioned inversion barriers of the A-t-butyl compounds lie markedly lower (104-110 kJ moF ). Thus, the A-t-butyloxaziridine derived from adamantanone loses half of its chirality within 2.3 days at 20 C (73JCS(P2)1575). 

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