Menthol, Amino

In y-alkoxyfuranones the acetal functionality is ideally suited for the introduction of a chiral auxiliary simultaneously high 71-face selectivity may be obtained due to the relatively rigid structure that is present. With ( + )- or (—(-menthol as auxiliaries it is possible to obtain both (5S)- or (5/ )-y-menthyloxy-2(5//)-furanones in an enantiomerically pure form293. When the auxiliary acts as a bulky substituent, as in the case with the 1-menthyloxy group, the addition of enolates occurs trans to the y-alkoxy substituent. The chiral auxiliary is readily removed by hydrolysis and various optically active lactones, protected amino acids and hydroxy acids are accessible in this way294-29s-400. 

Fischer alkenylcarbene complexes undergo cyclopentannulation to alkenyl AT,AT-dimethylhydrazones (1-amino-1-azadienes) to furnish [3C+2S] substituted cyclopentenes in a regio- and diastereoselective way along with minor amounts of [4S+1C] pyrrole derivatives. Enantiopure carbene complexes derived from (-)-8-(2-naphthyl)menthol afford mixtures of trans,trans-cycloipentenes and ds,ds-cyclopentenes with excellent face selectivity [75]. The mechanism proposed for the formation of these cyclopentene derivatives is outlined in Scheme 28. The process is initiated by nucleophilic 1,2-attack of the carbon... 

Das aus (-)-Menthol hergestellte chirale Hydrid liefert in erster Linie mit zweizahnigen Substraten [fi-Amino- ketone, En-(2)-in-(4)-ole (s.S. 74)] gute optische Ausbeuten1. Als chirale vie. Diole werden Zucker-2,1 und Terpen-Derivate wie cis- und rrans-Pinandiol-(2,3)4 verwendet. Von den Zucker-Derivaten hat sich der Kom-plex mit 3-0-Benzyl-l,2-0-cyclohexyliden-a-D-glucofuranose am besten bewahrt2,5 (Vorschrift S. 74). 

In 1990, Choudary [139] reported that titanium-pillared montmorillonites modified with tartrates are very selective solid catalysts for the Sharpless epoxidation, as well as for the oxidation of aromatic sulfides [140], Unfortunately, this research has not been reproduced by other authors. Therefore, a more classical strategy to modify different metal oxides with histidine was used by Moriguchi et al. [141], The catalyst showed a modest e.s. for the solvolysis of activated amino acid esters. Starting from these discoveries, Morihara et al. [142] created in 1993 the so-called molecular footprints on the surface of an Al-doped silica gel using an amino acid derivative as chiral template molecule. After removal of the template, the catalyst showed low but significant e.s. for the hydrolysis of a structurally related anhydride. On the same fines, Cativiela and coworkers [143] treated silica or alumina with diethylaluminum chloride and menthol. The resulting modified material catalyzed Diels-Alder reaction between cyclopentadiene and methacrolein with modest e.s. (30% e.e.). As mentioned in the Introduction, all these catalysts are not yet practically important but rather they demonstrate that amorphous metal oxides can be modified successfully. 

Coordination of the aluminum atom of the reducing complex was proposed to take place both to the oxygen atom of the hydroxy group and to the nitrogen atom of the amino group. The asymmetric reduction of enamine perchlorates and ketimines with menthol and bomeol chiral auxiliary reagents (50,51) presumably involves coordination of aluminum to the nitrogen atom of the substrate. 

Stereospecific nucleophilic substitution in chiral ion—dipole complexes. Chiral molecules can be discriminated in the Cl source of a CIMS instmment by specific ion-molecule reactions induced by chiral reagent gas. This method has been applied with success to distinguish between enantiomeric and diastereomeric forms of menthols ((lR,2S,5R)-(— )-14, (lS,2R,5S)-(+)-14, and (lR,2R,5S)-(—)-14 in Scheme 11) through the nucleophilic displacement of their hydroxyl group by (5)-2-amino-l-butanol Self-protonation of As... 

Fig. 20 MIKE/CID spectra of the substituted m/z228 ions from the enantiomers of menthol ((7/ ,25,5R)-(— )-14 (A) and (75,27 ,55)-(+)-14 (B)) formed under CE(5)-2-amino-l-butanol (As) conditions (the m/z2 0 and mlz90 daugther ions are also produced during unimolecular decomposition of the m/z228 ions) (reprinted from ref. 472, with permission from Elsevier).

To our knowledge, the first examples of asymmetrically substituted monocyclic phosphoranes are 60 and 61, described by Moriarty et al.135 and involving the reaction of a substituted o-benzoquinone136,137 (Scheme 6) on an aminophosphine (59), itself obtained by alcoholysis of 58 with l-( — )-menthol. In contrast to the amino phosphine 53 (Scheme 5), 59 is a mixture of the diastereoisomers 59a and b, and its reaction with 3,5-di-tert-butyl-l,2-benzoquinone yields two diastereoisomeric phosphoranes, 60a and b. Finally, alcoholysis of the P(V)—NR2 bond138 in 60a and b leads to 61a and b or 62. 

Boron enolates bearing menthol-derived chiral ligands have been found to exhibit excellent diastereo- and enantio-control on reaction with aldehydes34 and imines.35 Highly diastereo- and enantio-selective aldol additions of geometrically defined trichlorosilyl ketone enolates (31) and (32) have been achieved by promoting the reactions with chiral Lewis bases, of which (S,S)-(33) proved to be the most effective.36 Moderate enantiomeric excesses have been achieved by using chiral amino alcohols as catalysts for the Baylis-Hillman condensation of aldehydes with methyl vinyl ketone the unexpected pressure effect on the reaction has been rationalized.37... 

Amino acylations.1 This salt is far more reactive, particularly for O-acylation, than N,N -carbonyldiimidazole. Thus it effects esterification of N-Cbz protected amino acids with even hindered alcohols such as /-menthol in 98% yield without need of a base and, consequently, free from racemization. It also can effect coupling of amino acids in high yields and without racemization. 

They made a racemic sample using the Strecker synthesis of amino acids that you met in Chapter 12. The racemic amino acid was reacted with acetic anhydride to make the mixed anhydride and then with the sodium salt of naturally derived, enantiomerically pure alcohol menthol to give two diastereoisomers of the ester (see top of facing page). 

Chiral catalysis is employed in several industrial processes leading to enan-tiomerically pure products, such as the amino acid L-dihydroxyphenylalanine (L-DOPA) required for the treatment of Parkinson s disease, L-menthol, and car-bapenems.7 8 The hydrogenation of prochiral functionalized alkenes, notably a-acetamidocinnamic esters, has attracted particular attention ... 

Hydroperoxide-n-Butyllithium gives 50% de. Chiral 3-amino esters of 8-phenylmenthol have been prepared in 50-60% de by the addition of amines to the re face of 8-phenylmenthyl crotonate under 14-15 kbar pressures (eq 2). Much higher (75 to >99%) de is obtained using 8-0-naphthyl)menthol crotonate. The 3-amino esters obtained are of the proper configuration for conversion to biologically active 3-lactams. ... 

Hamon and co-workers disclosed the asymmetric synthesis of non-proteinogenic a-amino acids [27], The authors used A -protected imino menthol esters as the building blocks (see Table 3, entry 3). They expected that 1,2-addition to the imine would take place, rather than attack at the nitrogen, because of the presence of the acyl group. The... 

Phenol is incompatible with albumin and gelatin as they are precipitated. It forms a liquid or soft mass when triturated with compounds such as camphor, menthol, thymol, acetaminophen, phenacetin, chloral hydrate, phenazone, ethyl amino-benzoate, methenamine, phenyl salicylate, resorcinol, terpin hydrate, sodium phosphate, or other eutectic formers. Phenol also softens cocoa butter in suppository mixtures. 

The GC separation of enantiomeric d- and L-amino acids with nonchiral phases requires their conversion to diastereomeric derivatives. The second asymmetric center in the molecule ( ) arises after esterification by optically active alcohols [2-BuOH, 2-AmOH, pinacolol, (-)-menthol, etc.] or NH2 group acylation by chiral reagents e.g., a-methoxy-a-trifiuoromethylphenylacetyl chloride [MTPAC (IV)], A-trifiuoroacetyl-L-prolyl chloride [N-TFA-L-Pro-Cl (V)], A-trifiuoroacetyl-thiazolidine-4-carbonyl chloride (VI), etc. ... 

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