Chiral menthol

Brunner et al. [26] synthesized and applied so-called dendrizymes in enan-tioselective catalysis. These catalysts are based on dendrimers which have a functionalized periphery that carries chiral subunits, (e.g. dendrons functionalized with chiral menthol or borneol ligands). The core phosphine donor atoms can be complexed to (transition) metal salts. The resultant dendron-enlarged 1,2-diphosphino-ethane (e.g. 16, see Scheme 17) Rh1 complexes were used as catalysts in the hydrogenation of acetamidocinnamic acid to yield iV-acetyl-phenylalanine (Scheme 17) [26]. A small retardation of the hydrogenation of the substrate was encountered, pointing to an effect of the meta-positioned dendron substituents. No significantly enantiomerically enriched products were isolated. However, a somewhat improved enantioselectivity (up to 10-11% e.e.) was... 

The use of Lewis acids in controlling the stereoselective outcome of radical cyclization reactions has been explored, in particular the effect of aluminium-based Lewis acids using low temperature Et3B/Bu3SnH-initiated procedures.171,172 For example, cyclization of propargyl ether (78) or allyl ether (79) in the presence of Lewis acid (80) can completely reverse the normal selectivity (Scheme 34).171 The effect of aluminium Lewis acids on the diastereoselectivity of 6-exo cyclization of unsaturated chiral menthol esters has been studied.172 Cyclization at low temperature in the presence of the Lewis acid MAD modified the de of the reaction from 31 to 98%. 

A chiral menthol auxiliary has been utilized by Hoffmann and coworkers for the radical addition/cyclization reaction of N,N-dimethylaniline 242 with 5R)-menthyloxyfuran-2(5H)-one 245 using photochemical electron transfer (PET). The reaction led to 246 and 247 with 44% yield and 3.3 1 diastereoselectivity [77, 78] (Scheme 5.52). A modified menthol auxiliary was utilized for the asymmetric synthesis of a chiral precursor to the natural terpenoid (+)-triptocallol by Yang and coworkers [79]. The reaction was performed under oxidative radical conditions mediated by l.Oequiv of Yb(OTf)3 and 2.2equiv of Mn(0Ac)3-2H20 Mn(OAc)3. Reasonable yields of 55-72% and a diastereoselectivity of 24.2 1-2.8 1 were... 

In an analogous series, surfactants derived from 6-aminopenicillanic acid but bearing only hydrogenated substituents [98] have been synthesized, with yields of ca. 50%. One of the aims of these preparations is to access amphiphilic substances useful for chiral recognition [99,100], We have recently attempted the enantioselective synthesis of the p-perfiuoroalkyl-P-alanines (42). The enantiomeric excess achieved is rather modest for the moment. The approach is described in Scheme 36, with the enantioselective step being the hydrogenation of the chiral menthol ester. 

Ito, Katsuki, and coworkers reported the asymmetric Diels-Alder reaction between 3-crotonoyl-2-oxazoIidone and cyelopentadiene with chiral menthol 35-AlEt2Cl complex as the catalyst (Scheme 19.44). ° A reversal of... 

L-Menthol [2216-51-5] (75) and D-menthol [15356-70-4] have been used as chiral auxiharies in the synthesis of optically active mandehc acids. Reduction of (-)-menthol ben2oylfomiate (76) with a stericaHy bulky reducing agent, ie, sodium bis(2-methylethoxy)aluminum hydride (RED-Al), followed by saponification, yields (R)-mandelic acid (32) of 90% ee. 

Danishefsky et al. were probably the first to observe that lanthanide complexes can catalyze the cycloaddition reaction of aldehydes with activated dienes [24]. The reaction of benzaldehyde la with activated conjugated dienes such as 2d was found to be catalyzed by Eu(hfc)3 16 giving up to 58% ee (Scheme 4.16). The ee of the cycloaddition products for other substrates was in the range 20-40% with 1 mol% loading of 16. Catalyst 16 has also been used for diastereoselective cycloaddition reactions using chiral 0-menthoxy-activated dienes derived from (-)-menthol, giving up to 84% de [24b,c] it has also been used for the synthesis of optically pure saccharides. 

Perhaps the most successful industrial process for the synthesis of menthol is employed by the Takasago Corporation in Japan.4 The elegant Takasago Process uses a most effective catalytic asymmetric reaction - the (S)-BINAP-Rh(i)-catalyzed asymmetric isomerization of an allylic amine to an enamine - and furnishes approximately 30% of the annual world supply of menthol. The asymmetric isomerization of an allylic amine is one of a large and growing number of catalytic asymmetric processes. Collectively, these catalytic asymmetric reactions have dramatically increased the power and scope of organic synthesis. Indeed, the discovery that certain chiral transition metal catalysts can dictate the stereo-... 

The interest in asymmetric synthesis that began at the end of the 1970s did not ignore the dihydroxylation reaction. The stoichiometric osmylation had always been more reliable than the catalytic version, and it was clear that this should be the appropriate starting point. Criegee had shown that amines, pyridine in particular, accelerated the rate of the stoichiometric dihydroxylation, so it was understandable that the first attempt at nonenzymatic asymmetric dihydroxylation was to utilize a chiral, enantiomerically pure pyridine and determine if this induced asymmetry in the diol. This principle was verified by Sharpless (Scheme 7).20 The pyridine 25, derived from menthol, induced ee s of 3-18% in the dihydroxylation of /rcms-stilbene (23). Nonetheless, the ee s were too low and clearly had to be improved. 

A similar but asymmetric variant of the reaction, involving the radical addition of alkyl iodides and trialkylboranes to chiral azirine esters derived from 8-phenyl-menthol and camphorsultam, in the presence of a Cu(i) catalyst, has subsequently been reported [64]. The diastereoselectivity of the addition is variable (0-92% de)... 

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. 

Chiral alcohols have also been used in an asymmetric synthesis of sulphoxides based on halogenation of sulphides. Johnson and coworkers have found319 that the reaction of benzyl p-tolyl sulphide with JV-chlorobenzotriazole (NCBT) followed by addition of (—) menthol and silver tetrafluoroborate afforded diastereoisomeric menthoxysulphonium salts 267 which, upon recrystallization and hydrolysis, gave benzyl p-tolyl sulphoxide with 87% optical purity (equation 145). More recently, Oae and coworkers reported320 that optically active diaryl sulphoxides (e.e. up to 20%) were formed either by hydrolysis or thermolysis of the corresponding diaryl menthoxysulphonium salts prepared in situ from diaryl sulphides using ( —) menthol and t-butyl hypochlorite. 

The Diels-Alder reaction of simple alkoxy alkenylcarbene complexes leads to mixtures of endo and exo cycloadducts, with the endo isomer generally being the major one [96,97]. Asymmetric examples of endo Diels-Alder reactions have also been reported by the use of chiral auxiliaries both on the carbene complex and the diene. Thus, the reaction of cyclopentadiene with chiral alkenylcarbene complexes derived from (-)-menthol proceeds to afford a 4 1... 

A chiral version of this [4+3] heterocyclisation was achieved using chiral, non-racemic carbene complexes derived from menthol and oximes as depicted... 

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). 

Differences in chirality of substrate, and nature of solvent, have no effect on the competitive nature of the displacement of 0-alkyl and S-methyl groups in the reactions between (+)-pinacolyl alkoxide and 0-ethyl (and methyl) S-methyl methylphosphonothioates (Scheme 23). For the (R)-( + ) esters, e.g. (210), the displacements are highly stereoselective and occur with configurational inversion,but the enantiomeric esters do not display such stereoselectivity. (-)-Menthol might be considered a mirror image of (S)-pinacol, and similar reactions with the sodium salt of (-)-menthol occur highly stereoselectively... 

Takasago A catalytic process for the enantioselective isomerization of allylic amines. The catalyst is a chiral rhodium complex. Used in the manufacture of (-)menthol. Named after Takasago International Corporation, the Japanese company which commercialized the process in 1983. 

The synthesis of a variety of chiral aliphatic aldehydes of high optical purity through the enantioselective isomerization of allylamines found many applications in organic synthesis. The enantioselective isomerization of diethylgeranylamine, which was prepared from myrcene, furnished (R, )-diethylenamine in >98% yield with >98% ee. This enamine is converted to (—(-menthol stereospecifically in high chemical yield (yield of each step >92%, Scheme 4).9 11... 

Besides the phosphite ligands based on BINOL, phosphite ligands based on bisphenol are also used in rhodium-catalyzed hydrogenation. These ligands are shown in Scheme 28.7 and consist of a bisphenol with different substituents on the 3,3, 5,5, and 6,6 -positions. The ligands without substituents on the 6,6 -positions are only fluxionally chiral. The use of readily available chiral alcohols (21 aa-21 aj) such as menthol in combination with bisphenol was thought to induce one of the bisphenol conformations in preponderant amounts [49]. The... 

For acrylates, or type I reagents, applied in asymmetric Diels-Alder reactions, several chiral auxiliaries such as menthol derivatives, camphor derivatives,16,3 and oxazolidinones4 are available. Carbohydrate compounds have also been reported as chiral auxiliaries in a recent publication, although the stereoselectivity was not good.5 Here are examples in which asymmetric Diels-... 

Early work on the asymmetric Darzens reaction involved the condensation of aromatic aldehydes with phenacyl halides in the presence of a catalytic amount of bovine serum albumin. The reaction gave the corresponding epoxyketone with up to 62% ee.67 Ohkata et al.68 reported the asymmetric Darzens reaction of symmetric and dissymmetric ketones with (-)-8-phenylmenthyl a-chloroacetate as examples of a reagent-controlled asymmetric reaction (Scheme 8-29). When this (-)-8-phenyl menthol derivative was employed as a chiral auxiliary, Darzens reactions of acetone, pentan-3-one, cyclopentanone, cyclohexanone, or benzophenone with 86 in the presence of t-BuOK provided dia-stereomers of (2J ,3J )-glycidic ester 87 with diastereoselectivity ranging from 77% to 96%. 

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