Reducing chiral

Mukaiyama rationalized this low selectivity by invoking the facile formation of benzylic oxonium cations which prefer to react via SN 1-type transition states with reduced chiral induction. His catalyst was prepared in situ by the addition of silver triflate to chlorodiphenylborane in a 1 1 ratio. 

Catecholborane stereoselectively reduces chiral 7-amino-/3-ketophosphonates 93 and /3-amino-cr-ketophosphonates 95 yielding the l,2-ty -aminoalcohols 94 and 96 in high selectivity (Scheme 14) <1999TL7705, 2002TA559>. 

The most widely studied approach for the enantioselective hydrogenation of non-functionalized alkenes has been the use of reduced chiral titanocene complexes. The initial promising demonstration utilized bis(menthylcyclopentadi-enyl)titanium dichloride (12) in the presence of Red-Al to catalyze the hydrogenation of 2-phenylbutene in 23% ee (determined by optical rotation) [13,14, 15]. Two mechanisms have been postulated for hydrogenations involving reduced titanocene catalysts a Ti(II)/Ti(IV) cycle and the more commonly invoked Ti(III) cycle shown in Scheme 2. 

The reaction of butenolides or a,P-unsaturated lactams (35 X = O or NBoc) reacts with ethylene diamine to form the reduced chiral 7-(a-hydroxyalkyl)- and... 

Scheme 11.3 Synthesis of zeolite supported chiral catalyst. The chiral catalyst promotes various aliphatic and aromatic ketone reductions to their reduced chiral secondary alcohols. A summary of the examples have been summarized in Table 11.4.

Figure 7.15. Theoretical phase diagram showing temperature t versus squared electric field in reduced units. The phase diagram is for reduced chirality k= 1.7 results to the left (right) of the dashed line correspond to < 0 > 0)- Shown...

Asymmetric reduction of unsymmetrically substimted 1,2-diketones with the chiral Ru catalyst gives a partly reduced chiral a-hydroxy ketone at 10°C, while at higher temperature, 40°C, chiral ann-1,2-diols with an excellent ee is obtainable (Fig. 5) [34]. This method can be applied to access (l/ ,2S)-l-(4 -methoxyphenyl)-1,2-propanediol (98% ee), which is a major metabolite of fran -anethole in the rat. 

For a series of esters of propranolol, esterases from different tissues displayed varying rates of hydrolysis towards esters of the R and S forms of the drug. Plasma esterases hydrolysed the R esters at about ten times the rate of the S esters, where the rate of hydrolysis was rapid (Table 5.6). In the case of the hindered piva-late ester the rate of hydrolysis was much slower and the chiral discrimination was much reduced. Chiral discrimination by liver and intestinal esterases favoured hydrolysis of the S esters but was less marked, reflecting... 

Several groups have studied the structure of chiral phases illustrated in Fig. IV-15 [167,168]. These shapes can be understood in terms of an anisotropic line tension arising from the molecular symmetry. The addition of small amounts of cholesterol reduces X and produces thinner domains. Several studies have sought an understanding of the influence of cholesterol on lipid domain shapes [168,196]. 

In cases where Noyori s reagent (see p. 102f.) and other enantioselective reducing agents are not successful, (+)- or (—)-chlorodiisopinocampheylborane (Ipc BCl) may help. This reagent reduces prochiral aryl and tert-alkyl ketones with exceptionally high enantiomeric excesses (J. Chandrasekharan, 1985 H.C. Brown, 1986). The initially formed boron moiety is usually removed hy precipitation with diethanolamine. Ipc2BCl has, for example, been applied to synthesize polymer-supported chiral epoxides with 90% e.e. from Merrifield resins (T. Antonsson, 1989). 

Asymmetric hydrogenolysis of allylic esters with formic acid with satisfactory ee was observed[387], Geranyl methyl carbonate (594) was reduced to 570 with formic acid using l,8-bis(dimethylamino)naphthalene as a base and MOP-Phen as the best chiral ligand, achieving 85% ee. 

The alkyl azide 118 is reduced to a primary amine by the Pd on carbon-catalyzed reaction of ammonium formate in MeOH at room temperature. No racemization takes place with chiral azides[l 11,112]. 

Section 7 12 For a particular constitution the maximum number of stereoisomers is 2" where n is the number of structural units capable of stereochemical variation—usually this is the number of chirality centers but can include E and Z double bonds as well The number of stereoisomers is reduced to less than 2" when there are meso forms... 

The reaction is used for the chain extension of aldoses in the synthesis of new or unusual sugars In this case the starting material l arabinose is an abundant natural product and possesses the correct configurations at its three chirality centers for elaboration to the relatively rare l enantiomers of glucose and mannose After cyanohydrin formation the cyano groups are converted to aldehyde functions by hydrogenation m aqueous solution Under these conditions —C=N is reduced to —CH=NH and hydrolyzes rapidly to —CH=0 Use of a poisoned palladium on barium sulfate catalyst prevents further reduction to the alditols... 

Ammonia reacts with the ketone carbonyl group to give an mine (C=NH) which is then reduced to the amine function of the a ammo acid Both mine formation and reduc tion are enzyme catalyzed The reduced form of nicotinamide adenine diphosphonu cleotide (NADPH) is a coenzyme and acts as a reducing agent The step m which the mine is reduced is the one m which the chirality center is introduced and gives only L glutamic acid... 

Chemical Properties. Because of its chiral center, malic acid is optically active. In 1896, when tartaric acid was first reduced to malic acid, the levorotatory enantiomer, S(—), was confirmed as having the spatial configuration (1) (5,6). The other enantiomer (2) has the R configuration. A detailed discussion of configuration assignment by the sequence rule or the R and S system is available (7). 

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. 

Industrial Synthetic Improvements. One significant modification of the Stembach process is the result of work by Sumitomo chemists in 1975, in which the optical resolution—reduction sequence is replaced with a more efficient asymmetric conversion of the meso-cyc. 02Lcid (13) to the optically pure i7-lactone (17) (Fig. 3) (25). The cycloacid is reacted with the optically active dihydroxyamine [2964-48-9] (23) to quantitatively yield the chiral imide [85317-83-5] (24). Diastereoselective reduction of the pro-R-carbonyl using sodium borohydride affords the optically pure hydroxyamide [85317-84-6] (25) after recrystaUization. Acid hydrolysis of the amide then yields the desired i7-lactone (17). A similar approach uses chiral alcohols to form diastereomic half-esters stereoselectivity. These are reduced and direedy converted to i7-lactone (26). In both approaches, the desired diastereomeric half-amide or half-ester is formed in excess, thus avoiding the cosdy resolution step required in the Stembach synthesis. 

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