Chiral alkaloid

The asymmetric Michael addition of 1,3-dicarbonyl compounds to nitrostyrene is promoted by chiral alkaloid catalysts to give the addition products in good chemical yield, but the enantioselectivity is rather low (Eq. 4.47).62... 

Matsumoto and coworkers have introduced a new strategy for asymmetric induction under high pressure. The Michael addition of nitromethane to chalcone is performed at 10 kbar in the presence of a catalytic amount of chiral alkaloids. The extent of asymmetric induction reaches up to 50% ee with quinidine in toluene.201... 

In a similar fashion to its reaction with the aldehydes, diethylzinc reacts with (N-diphenylphosphonyl)imines in the presence of chiral alkaloids to produce, after hydrolysis, chiral 2-substituted propylamines [42],... 

The cathodic reduction of 4-carboethoxy-coumarin in the presence of a catalytic amount of various chiral alkaloids can afford 4-carboethoxydihydrocoumarin in low enantiomeric excess (ee < 20%) (Scheme 140) [253]. In the... 

An asymmetric induction can be performed during the cathodic reduction of various substituted coumarins in the presence of chiral alkaloids. A mixture of dimers and dihydrocoumarins is obtained in various yields according to the nature of the alkaloids (31-89% of dimer and 5-67% of dihydrocoumarin with unsubstituted coumarin) [273]. 

A range of chiral alkaloids have been screened for the asymmetric reduction of 2- and 4-acetyl pyridine [41] and results are given in Table 10.5. Brucine and strychnine give the highest enantiomeric excess in the pyridinylethanols produced. Reduction of 3-acetylpyridine however affords no optically active alcohol under all conditions employed. A further effect of the added alkaloid is to raise the yield of secondary alcohol at the expense of the pinacols relative to reactions where no alkaloid is present. The high enantiomeric excess found during reduction of 4 ... 

As discussed previously, the chiral alkaloid (—)-sparteine (Scheme 33) forms a biden-tate complex with compounds such as butyllithium, and this chiral base can distinguish... 

In an effort to synthesize the chiral alkaloid, optically active 37 was prepared by chemical resolution, but both enantimoers were partially racemized when reacted with potassium amide in ammonia. Efforts to resolve ( )-39 failed to give the desired enantiomer. 

A, CuCl, chiral alkaloid (enantioselective) hydrolysis/A, Cu20 DABCO, MeaS, Celite, A (Me4N)OAc, DMSO (Me4N)OAc, HMPA... 

Asymmetric induction during the reduction of 4-(48) was observed when a surface-modified carbon cathode was used.70 Optical yields were low but the effect of the chiral amino acid bound to the carbon surface was proved to be a true surface phenomenon. Induction of chirality by homogeneous rather than surface-bound agents has also been studied.71 All the isomeric acetylpyridines (48) were reduced in the presence of three different chiral alkaloids. Both carbinol products 2- and 4-(49) were shown to possess induced chirality, but the 3-carbinol (49) had none under any of the conditions tried. More rapid protonation of the intermediate was proposed to account for the lack of induced chirality. Optimization of optical yields was done.72 The pinacols (50) formed along with 49 were found to have no induced chirality. Optical yields have been as high as 50%.73 The role of electroabsorption was found to be important in the reduction of 2-(48).74 Product distributions were noted as a function of surfactant present in the electrolyte, carbinol 49 being favored... 

The combination of K2[0s02(0H)4] or 0s04 with chiral alkaloid ligands affords highly recyclable systems for the dihydroxylation of olefins. Bis-Chinona alkaloid ligands containing phthalazine or pyrimidine backbones, as shown in Figure 5.8, provide superb enantioselectivity and different models have been devised to rationalise the chirality transfer/71,721... 

The intramolecular asymmetric Michael reaction of acyclic compounds obtained from chiral alkaloid building blocks using amines and (5)-proline has been investigated. " The Michael addition of dimethyl malonate to a,p-unsaturated aldehydes proceeds... 

The decarboxylation of amino acids is facilitated by copper Lewis acids. Treatment of tryptophan with copper(II) acetate in HMPA afforded tryptamine 117 in 45 % yield (Sch. 26) [58]. Chelation is thought to activate the carboxylate for elimination. The stable chelate can be isolated and undergoes decarboxylation when heated. An asymmetric version of a similar decarboxylation of malonate derivatives has been reported poor selectivity resulted from addition of chiral alkaloids [59]. 

Of particular mechanistic interest in AD is the question of how chirality is transmitted from the chiral alkaloid ligand to the Os glycolate complex [33]. 

Ujaque, G., Maseras, F., Lledos, A. A theoretical evaluation of steric and electronic effects on the structure of [0s04(NR3)] (NR3 = bulky chiral alkaloid derivative) complexes. Theor. Chim. Acta 1996, 94, 67-73. 

Very recently it has been shown that electrode surfaces can be chemically modified.13 Although no useful reactions have come from this work, it has been shown that organic molecules can be covalently attached to electrode surfaces and that these modified surfaces impart selectivity to electrochemical reactions which is not otherwise available. Attempts have also been made to increase the selectivity of electrochemical reactions by adsorbing material on the electrode surface. In particular if chiral alkaloids are adsorbed on mercury, it Is then possible to perform the asymmetric reduction of prochiral ketones tc chiral alcohols. An optical yield of 54% has, for example, been reported for the reduction of 4-acetyl pyridine in aqueous-ethanol using strychnine as the catalytic, chiral reagent.11 ... 

Equation 12.16 is an example of the Sharpless-Katsuki asymmetric epoxi-dation of allylic alcohols, which is catalyzed by a Ti complex bound to a chiral tartrate ligand.38 A Mn-salen39 complex serves as catalyst for asymmetric epoxi-dation (Jacobsen-Katsuki reaction) of a wide variety of unfunctionalized alkenes, shown in equation 12.17.40 0s04 complexed with chiral alkaloids, such as quinine derivatives (equation 12.18), catalyzes asymmetric 1,2-dihydroxylation of alkenes (known as the Sharpless asymmetric dihydroxylation).41 The key step of all these transformations is the transfer of metal-bound oxygen, either as a single atom or as a pair, to one face of the alkene. 

The even more sophisticated stereospecific formation of the chiral alkaloid 63 by Stevens and Lee [49], and the previous synthesis of 58 and related procedures have in common their essential ring-closing steps corresponding to unions of M-3CRs.The a-amino-alkylating MCRs of type I [4,7] correspond to collections of equilibrating subreactions. Such positive formation of polyheterocyclic products correspond to almost irreversible cyclocondensations. These elegant syntheses correspond to an area of preparative chemistry whose products can be formed successfully, and where unions of reversible MCRs can have virtually irreversible final steps. 

Chiral molecules on the surface of the metal colloid can induce enantioselective control. Following this concept a new type of enantioselective platinum sol catalyst stabilized by the alkaloid dihydrocinchonidine was designed [120, 121]. Chirally modified Pt catalyst precursors have been prepared in different particle sizes by the reduction of platinum tetrachloride with formic acid in the presence of different amounts of the chiral alkaloid. Optical yields up to 80% ee were obtained in the hydrogenation of ethyl pyruvate. This type of catalyst was demonstrated to be structure insensitive since turnover frequencies (ca. 1 s ) and enantiomeric excess are independent of the particle size. 

A unified discussion of supported asymmetric reactions is difficult because many different types of reaction have been investigated. Hodge has already produced a useful review recently [88] and this up-dates previous summaries [39, 89]. Asymmetric modification of alkenes is an important area, and although polymer-supported alkaloids, such as quinine, have been quite widely used in potentially asymmetric synthetic processes, the recent application to dihydroxylation of alkenes is an important step forward [90]. Here the polymer-bound chiral alkaloid has been used with OSO4 to achieve asymmetric dihydroxylation of trans-stil-bene and styrene. Chemical yields of 85% and enantiomeric excesses (ee) of up to 87% have been achieved. The chiral support was re-used once without addition of more OSO4 and with only a small drop in yield. Another new development involves iodolactonisation of pentenamide moieties bound to a chiral auxiliary consisting of (5)-2-pyrrolidine attached to... 

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