Menthyl amine

The preparative separations reported in the literature have been carried out using (S)-phenylalanine ethyl ester (a), (S)-l-cyclohexylethylamine (b) and menthyl amine (c) [49] as the chiral selector (Fig. 6.6). 

GuHbN Onantbyliden-iaoamybuuin 4,184. lO-Dimethylaniino-decen-(l) 4 1 397. Amylammo-l-methyl-crolohexan 18,10. Dimethyl-menthyl-amin 18, 27, Athyl-menthyl-amin 18, 27. Dimethyl-[d.(2.2.3-trimethyl-oyclopentyl)-fithyl]-a 18 II 38. 

C N AraohmsliUie-nitTil 2 II370. DM-menthyl.amin 12 1121, II26. Di.d.menthyl-amm 12, 29. 

For the regioselectivity similar rules as for the ester pyrolysis do apply. With simple, alkylsubstituted amine oxides a statistical mixture of regioisomeric olefins is obtained. On the other hand with cycloalkyl amine oxides the regioselectivity is determined by the ability to pass through a planar, five-membered transition state. This has been demonstrated for the elimination reaction of menthyl dimethylamine oxide 10 and neomenthyl dimethylamine oxide 11 ... 

Based on nucleophilic addition, racemic allenyl sulfones were partially resolved by reaction with a deficiency of optically active primary or secondary amines [243]. The reversible nucleophilic addition of tertiary amines or phosphanes to acceptor-substituted allenes can lead to the inversion of the configuration of chiral allenes. For example, an optically active diester 177 with achiral groups R can undergo a racemization (Scheme 7.29). A 4 5 mixture of (M)- and (P)-177 with R = (-)-l-menthyl, obtained through synthesis of the allene from dimenthyl 1,3-acetonedicar-boxylate (cf. Scheme 7.18) [159], furnishes (M)-177 in high diastereomeric purity in 90% yield after repeated crystallization from pentane in the presence of catalytic amounts of triethylamine [158], Another example of a highly elegant epimerization of an optically active allene based on reversible nucleophilic addition was published by Marshall and Liao, who were successful in the transformation 179 — 180 [35], Recently, Lu et al. published a very informative review on the reactions of electron-deficient allenes under phosphane catalysis [244]. 

The stoichiometric enantioselective reaction of alkenes and osmium tetroxide was reported in 1980 by Hentges and Sharpless [17], As pyridine was known to accelerate the reaction, initial efforts concentrated on the use of pyridine substituted with chiral groups, such as /-2-(2-menthyl)pyridine but e.e. s were below 18%. Besides, it was found that complexation was weak between pyridine and osmium. Griffith and coworkers reported that tertiary bridgehead amines, such as quinuclidine, formed much more stable complexes and this led Sharpless and coworkers to test this ligand type for the reaction of 0s04 and prochiral alkenes. 

PCC is used to remove menthyl substituents working as chiral auxiliaries—from amines.306 The oxidation of menthylamines with PCC leads to P-aminoketones that, on treatment with base, suffer a retro-Michael reaction leading to free amines. 

Z-Menthyl Isocyanate. Pickard and Littlebury 20-21 found that Z-menthyl isocyanate forms crystalline esters (urethanes) with many alcohols and phenols. The two diastereoisomeric urethanes from cZZ-l-phenyl-1-p-hydroxyphenylethane and from dZ-oc-tetrahydro-/3-naphthol were separated readily.2 The method has not been applied widely. Z-Men-thyl isocyanate is the most readily available resolving agent of this type but is difficult to prepare. The urethanes are not easily hydrolyzed, and the isocyanate is not recovered in the hydrolysis but is converted to the amine. 

The principles outlined above were allied by Marckwald and McKenzie 18 for the partial resolution of a racemic acid with an active alcohol. Thus When df-mandelic acid was heated with less than one equivalent of 1-menthol, the resulting ester contained somewhat more J-menthyl-d-mandelate than f-menthyl-L-mandelate and the unesterified acid contained a corresponding excess of i-mandelic acid. Also, when a mixture of equal amounts of the two diastereoisomeric esters was partially hydrolyzed, the regenerated acid and that still combined in the residual ester contained unequal amounts of the two antipodes. The process has been extended to the resolution of acids and amines through the formation and hydrolysis of amides.89... 

To analyze the optical purity of a naproxen product, the material is first converted to a (+)- menthyl ester by reacting it with excess of (+)-menthol in the presence of dicyclohexylcarbodiimide and an amine catalyst. The resulting material is analyzed on a Varian 370 GC with a 25-meter Chrompack Chirasil-L-Val column. 

Heathcook et al. have performed a diastereoselective aza-ene reaction using chiral di-(+)-menthyl diazenedicarboxylate 91 as the nitrogen source [54]. Compound 91 was found to react with various alkenes in the presence of 2 equiv. SnCl4, and the corresponding allylic aminated product was obtained in good yield and with de up to 42 %. The problem with this approach was the removal of the chiral menthyl ester auxiliary, which was found to be rather difficult. 

For GC, the two most useful chiral reagents are /V-trifluoroacetyl-L-prolyl chloride (TCP) and menthyl chloroformate (MCF). TCP is used for the resolution of amines and MCF for alcohols. At best the reagents are 99% optically pure, but they can be as little as 90% pure. 

Related Reagents. The synthesis of chiral diazenedicarboxylates as potential chiral electrophilic aminating agents has received little attention. A series of chiral bomyl, isobomyl and menthyl diazenedicarboxylates has been reported and their reaction with achiral enolates of esters and N,N-dimethyl amides afforded a-hydrazino acid derivatives with little or no selectivity. Incorporation of a chiral azodicarboxamide unit into a chiral bridging binaphthyl moiety afforded a-hydrazino acid derivatives with high stereoselectivity in reactions with achiral oxazolidinone anions. ... 

Chiral )V-benzylidene p-toluenesulfinamides were prepared by reaction of benzonitrile with an alkyllithium followed by addition of (—)-menthyl (S)-p-toluenesulfinate and converted into optically active amines and amino acids (eq 19). ... 

Work carried out in our laboratories over the past three years and in conjunction with the research group of Daktemieks at Deakin University has been directed toward the development of novel enantiomerically pure stannanes for use in free-radical reduction chemistry. To that end Dunn prepared a series of menthyl-substituted stannanes 18 -20 and some others derived from aromatic amines (eg. 21, 22).Perchyonok tested these reagents against a series of substrates while Henry modelled the reactions in question through the use of ab initio molecular orbital theory. 

Unfortunately, the complexes underwent facile epimerization under the condi tions of catalytic hydroamination via reversible protolytic cleavage of the metal cyclopentadienyl bond (Scheme 11.7) [36, 38 40]. Thus, the product enantioselec tivity was limited by the catalyst s epimeric ratio in solution and the absolute configuration of the hydroamination product was independent of the diastereomeric purity of the precatalyst. Complexes with a (+) neomenthyl substituent on the cyclopentadienyl ligand generally produced the R) ( ) pyrrolidines, whereas ( ) menthyl and ( ) phenylmenthyl substituted complexes yielded the (S) (+) pyrrolidines, which is in agreement with the proposed stereomodel and solution studies on the equilibrium epimer ratios in the presence of simple aliphatic amines. 

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