Chiral methyl groups transfer

In situations where the third hydrogen required to convert a methylene into a methyl group comes from the same substrate, it is possible to determine by the chiral methyl group methodology whether this hydrogen is transferred inter-... 

The first account of the transfer of an intact methyl group was reported by Phillips and Clifford (60). Their study determined the steric course of the methyl group rearrangement from C-14 to C-13 in lanosterol biosynthesis. This enzymatic carbonium ion rearrangement occurred with retention of configuration of the migrating chiral methyl group. 

The laboratories of Floss and Arigoni laid the experimental foundation for the stereochemical analysis of methyl group transfer reactions, on the basis of the synthesis from chiral [ H, H, H]acetate of methionine and S-adenosylmeth-ionine carrying a chiral [ H, H, H]methyl group [335, 341), for example. 

In the study presented in Reference 15, we focused our attention on spontaneous processes of chiral conversion and peptidization running in aqueous acetonitrile solution of L-Met (Scheme 19.3). We chose this amino acid due to its important functions in the human body. L-Met is a donor of methyl groups in the metabolic processes of methyl group transfer it plays an important role in synthesis of choline and lecithin, promotes normalization of lipid metabolism and hepatic steatosis, and has an anti-atherosclerotic activity. Furthermore, L-Met plays an important role in the activities of the adrenal gland, in particular in the synthesis of adrenaline, and in the processes of inactivation of catecholamines, thereby regulating the catecholamine balance. The existence of a close relationship has also been proven between L-Met, folate transformations, and vitamins B6 and B12 [25]. 

Thus, chiral organotitanium compounds result from the use of (trialkoxy)chlorotitanates derived from chiral alcohols. The transfer of methyl and phenyl groups by chiral titanium... 

Roland et al. obtained 23% ee in the addition of Et2Zn to cyclohexenone using the silver(I) complex 78 having a chiral backbone and methyl groups on the nitrogen atoms. This complex acts as an efficient carbene transfer agent towards Cu(OTf)2. The conjugate addition proceeds rapidly in toluene at 0 °C (Scheme 52). 

Considerable ingenuity was required in both the synthesis of these chiral compounds695 697 and the stereochemical analysis of the products formed from them by enzymes.698 700 In one experiment the phospho group was transferred from chiral phenyl phosphate to a diol acceptor using E. coli alkaline phosphatase as a catalyst (Eq. 12-36). In this reaction transfer of the phospho group occurred without inversion. The chirality of the product was determined as follows. It was cyclized by a nonenzymatic in-line displacement to give equimolar ratios of three isomeric cyclic diesters. These were methylated with diazomethane to a mixture of three pairs of diastereoisomers triesters. These dia-stereoisomers were separated and the chirality was determined by a sophisticated mass spectrometric analysis.692 A simpler analysis employs 31P NMR spectroscopy and is illustrated in Fig. 12-22. Since alkaline phosphatase is relatively nonspecific, most phosphate esters produced by the action of phosphotransferases can have their phospho groups transferred without inversion to 1,2-propanediol and the chirality can be determined by this method. 

Metal-based asymmetric phase-transfer catalysts have mainly been used to catalyze two carbon-carbon bond-forming reactions (1) the asymmetric alkylation of amino acid-derived enolates and (2) Darzens condensations [5]. The alkylation ofprochiral glycine or alanine derivatives [3] is a popular and successful strategy for the preparation of acyclic a-amino acids and a-methyl-a-amino acids respectively (Scheme 8.1). In order to facilitate the generation of these enolates and to protect the amine substituent, an imine moiety is used to increase the acidity of the a-hydrogens, and therefore allow the use of relatively mild bases (such as metal hydroxides) to achieve the alkylation. In the case of a prochiral glycine-derived imine (Scheme 8.1 R3 = H), if monoalkylation is desired, the new chiral methine group... 

Very recently, Maruoka and co-workers described a new N-spiro quaternary ammonium bromide with two chiral biphenyl structures as easily modifiable subunits [37]. These phase-transfer catalysts with biphenyl subunits, containing methyl groups in the 6,6 -position for inducing chirality, and additionally bulky substituents in the 4-position, efficiently catalyzed the alkylation of protected glycinate with high enantioselectivity of up to 97% ee. The substrate range is broad, for example (substituted) benzyl bromide and allylic and propargylic bromides are tolerated [37]. 

When chiral substrates were employed in the cascade reaction, good transfer of the chiral information was observed (Scheme 7.43).119 Excellent diastereoselectivity was obtained with 152g, containing an allylic methyl group and even 152h, which contained a benzyl ether substituent that would lie outside the chairlike transition state (TS-156), controlled the facial selectivity of the [3,3]-sigmatropic rearrangement. 

A great number of chiral TTFs have been prepared [31,32], and some of their charge transfer salts have been crystallised. The 7r-donor 1 can be elec-trocrystallised to give a salt 12 PF6, which has a conductivity of 5 2 1 cm 1 at room temperature and metallic behaviour when cooled down [33]. While the structure of the crystals is chiral, the structure of this salt and other related ones [34] has an essentially achiral stack of donor molecules, which are pseudo-centrosymmetric [35]. The methyl groups at the periphery of the molecule are apparently not sufficient to cause a truly chiral stack of donors, which prefer to stack in parallel arrangements with partial overlap of the tr-systems in the solid state, a situation which is true for the majority of the efforts to prepare salts of this type (even if the salts are metallic). 

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