Stoichiometric diastereomer

Asymmetric catalytic osmylation.s Chiral cinchona bases are known to effect asymmetric dihydroxylation with 0s04 as a stoichiometric reagent (10, 291). Significant but opposite stereoselectivity is shown by esters of dihydroquinine (1) and of dihydroquinidine (2), even though these bases are diastereomers rather than enantiomers. 

An allene is a very promising unsaturated partner in cobalt-mediated [2 + 2 + 2]-cycloaddition reactions. Exposure of an allenediyne to a stoichiometric amount of CpCo(CO)2 in boiling xylenes under irradiation for 5 h furnishes red-brown complexes in 42% isolated yield (Scheme 16.76) [84—87]. Treatment of a 7 3 mixture of the two diastereomers thus obtained with silica gel provides an oxygen-sensitive cobalt-free tricydic compound. 

Sharpless stoichiometric asymmetric dihydroxylation of alkenes (AD) was converted into a catalytic reaction several years later when it was combined with the procedure of Upjohn involving reoxidation of the metal catalyst with the use of N-oxides [24] (N-methylmorpholine N-oxide). Reported turnover numbers were in the order of 200 (but can be raised to 50,000) and the e.e. for /rara-stilbene exceeded 95% (after isolation 88%). When dihydriquinidine (vide infra) was used the opposite enantiomer was obtained, again showing that quinine and quinidine react like a pair of enantiomers, rather than diastereomers. 

Chiral allenylmetal compounds provide convenient access to enantioenriched homopropargylic alcohols through Se2 additions to aldehydes. The syn adducts can be obtained through addition of allenyl tributylstannanes in the presence of stoichiometric boron trifluoride etherate (BF3-OEt2). The use of allenylmetal halides derivatives of Sn, Zn, and In lead to the anti diastereomers. The former additions proceed through an acyclic transition slate whereas the latter are thought to involve a cyclic transition state, thus accounting for the difference in diastereoselectivity. 

In 1996, Enders and coworkers reported the asymmetric epoxidation of ( )-enones 91 in the presence of stoichiometric amounts of diethylzinc and (lR,2R)-A-methylpseudo-ephedrine (120) under an oxygen atmosphere to give fraw -epoxides 92 with excellent yields (94-99%), almost complete diastereoselectivity (>98% de) and with very good enantioselectivities (61-92%) (Scheme 54) . For the same reaction Pu and coworkers utilized achiral polybinaphthyl 121 as ligand (in excess) instead of the chiral aminoalcohol. For each substrate, only one diastereomer was formed, but in most cases yields were lower than observed with the Enders system. Enders catalyst shows high asymmetric induction for alkyl-substituted enones (ee 82-92%), but for substrates bearing only aromatic substituents only modest enantioselectivity was obtained (R = R = Ph ... 

Widenhoefer and co-workers have developed an effective Pd-catalyzed protocol for the asymmetric cyclization/ hydrosilylation of functionalized 1,6-dienes that employed chiral, non-racemic pyridine-oxazoline ligands." " " Optimization studies probed the effect of both the G(4) substituent of the pyridine-oxazoline ligand (Table 7, entries 1-6) and the nature of the silane (Table 7, entries 6-15) on the yield and enantioselectivity of the cyclization/ hydrosilylation of dimethyl diallylmalonate. These studies revealed that employment of isopropyl-substituted catalyst (N-N)Pd(Me)Gl [N-N = (i )-( )-4-isopropyl-2-(2-pyridinyl)-2-oxazoline] [(i )-43f and a stoichiometric amount of benzhydryldimethylsilane provided the best combination of asymmetric induction and chemical yield, giving the corresponding silylated cyclopentane in 98% yield as a single diastereomer with 93% ee (Table 7, entry 15). 

Mori has reported the nickel-catalyzed cyclization/hydrosilylation of dienals to form protected alkenylcycloalk-anols." For example, reaction of 4-benzyloxymethyl-5,7-octadienal 48a and triethylsilane catalyzed by a 1 2 mixture of Ni(GOD)2 and PPhs in toluene at room temperature gave the silyloxycyclopentane 49a in 70% yield with exclusive formation of the m,//7 //i -diastereomer (Scheme 14). In a similar manner, the 6,8-nonadienal 48b underwent nickel-catalyzed reaction to form silyloxycyclohexane 49b in 71% yield with exclusive formation of the // /i ,// /i -diastereomer, and the 7,9-decadienal 48c underwent reaction to form silyloxycycloheptane 49c in 66% yield with undetermined stereochemistry (Scheme 14). On the basis of related stoichiometric experiments, Mori proposed a mechanism for the nickel-catalyzed cyclization/hydrosilylation of dienals involving initial insertion of the diene moiety into the Ni-H bond of a silylnickel hydride complex to form the (7r-allyl)nickel silyl complex li (Scheme 15). Intramolecular carbometallation followed by O-Si reductive elimination and H-Si oxidative addition would release the silyloxycycloalkane with regeneration of the active silylnickel hydride catalyst. 

Intramolecular [2 + 2 + 2] cycloadditions belong to the same type of valence isomerization as those of 1,5-unsaturated compounds to cyclobutanes.70 The cobalt-mediated cyclization of l-en-5-ynes stereoselectively converts enediynes directly to bicyclo[4.2.0]hexa-l,3-dienes, as single diastereomers, when a stoichiometric amount of dicarbonyl(cyclopentadienyl)cobalt is used. This cyclization90 has a high efficiency (92%). An example is the synthesis of the protoilludane framework 23 from the enediyne precursor 22.71... 

Stoichiometric Reactions. In 1974, Touboul reported amazing selectivity in the controlled potential electrochemical reduction of the enone (Scheme 36) (63). While the dimerization of the enantiomerically pure enone gives solely the cis,threo,cis diol, the racemic compound behaves similarly to produce the racemic dimer with the same relative configuration and no other possible diastereomers. A radical anion intermediate... 

Taddol has been widely used as a chiral auxiliary or chiral ligand in asymmetric catalysis [17], and in 1997 Belokon first showed that it could also function as an effective solid-liquid phase-transfer catalyst [18]. The initial reaction studied by Belokon was the asymmetric Michael addition of nickel complex 11a to methyl methacrylate to give y-methyl glutamate precursors 12 and 13 (Scheme 8.7). It was found that only the disodium salt of Taddol 14 acted as a catalyst, and both the enantio- and diastereos-electivity were modest [20% ee and 65% diastereomeric excess (de) in favor of 12 when 10 mol % of Taddol was used]. The enantioselectivity could be increased (to 28%) by using a stoichiometric amount of Taddol, but the diastereoselectivity decreased (to 40%) under these conditions due to deprotonation of the remaining acidic proton in products 12 and 13. Nevertheless, diastereomers 12 and 13 could be separated and the ee-value of complex 12 increased to >85% by recrystallization, thus providing enantiomerically enriched (2S, 4i )-y-methyl glutamic add 15. 

On the basis of their observation that achiral 2,2 -bipyridyl promotes the reaction between crotyltrichlorosilane and benzaldehyde, the Barrett group screened chiral pyridine molecules as Lewis-base catalysts for this reaction [175]. The pyridinylox-azoline 164a was identified as the most efficient organocatalyst. In the presence of this catalyst, which was, however, used in stoichiometric amounts, asymmetric addition of (E)-crotyltrichlorosilane 158b to aldehydes gave the anti products (S,S)-159 in yields of 61-91% and with enantioselectivity from 36 to 74% ee (Scheme 6.76) [175], Diastereoselectivity is high, because only the anti diastereomers were obtained. Aromatic aldehydes and cinnamylaldehyde were used as substrates. 

The phosphorus-stabilized carbanion of 94 was generated at -100 °C with LDA (1.2 equiv.) in THF. Amination reactions were performed both with DTBAD and trisyl azide. Direct addition of a stoichiometric amount of DTBAD (1.1 equiv.) at -100 °C followed by acidic quench led to a mixture of hydrazino products 95 (major diastereomer indicated) in good yield and diastereoselectivity (Scheme 44). 

The stoichiometric and catalyzed hydroxyamination of norbornene afforded exclusively the exo-cw-diastereomer or 281,82. By contrast, the catalyzed, regioselective and diastereoselective reaction with ( —)-bornene afforded the e t7o-cw-diastereomer 383. 

Bicyclic diazenes, in which the diazcnc group is not activated by acyl substituents, can act as dienophiles in the Diels-Alder reaction with cyclic dienes only in the presence of a stoichiometric amount of tetrafluoroboric acid to give. V,/V"-bicyclic hydrazines 111 . When two diastereomers can be produced, due to the nonsymmetric dienophile (i.e., when n 2), a single diastereomer is obtained ( H-NMR studies). 

The optimum catalyst for cycloaddition of the A -crotyl dienophile 175 with cyclopentadiene was found to be that generated from diethylaluminum chloride and diol 187. On this basis, the reactions of dienophiles 189 and 181 were examined with cyclopentadiene and furan as indicated in Sch. 20. In addition, catalysts derived from two derivatives of diol 187 were also examined, as shown in Table 11 [43-45]. It was found that all three diols resulted in similar asymmetric induction, with the highest induction not exceeding that observed for the A -crotyl dienophile 175. The A -acrolyl dienophile 189 gave an 83 17 mixture of endo and exo diastereomers, with 21 % ee for the endo adduct, with a catalyst prepared from diol 187. The same catalyst gave 25 % ee for the cycloadduct of furan with 189 and 2 % ee for the adduct of cyclopentadiene and 191, although in the latter example an increase to 27 % ee is possible with sub-stoichiometric amounts of catalyst. 

Allylation of imines with allyltrimethylsilane usually requires a stoichiometric amount of a strong Lewis acid such as SnCl4, TiCLj, or BL, [413-419], Laschat et al. have reported that Snf h promotes the allylation of imines derived from aromatic aldehydes and galactopyranosylamine with low to high diastereoselectivity (Scheme 10.145) [413]. The preferred formation of the S-configured diastereomers can be rationalized by conformational fixation of the imines by SnCl4, which prohibits attack of the allylsilane from the Re side, that is, the front side of the imine. 

The concept itself of asymmetric synthesis, stoichiometric or catalytic, took a long time appear. One important step was the investigations of Fischer in 1894-1899 on the structure and stereochemistry of sugars [3,4,5]. He observed the formation of diastereomers on addition of HCN to the aldehyde function of... 

A classical approach to enantiopure compounds is the stoichiometric resolution of the enantiomers by formation of diastereomers with an enantiomerically pure auxiliary. Although several industrial processes are still based on this meth-... 

Guanti and coworkers have reported that catalytic amounts (0.1 equiv.) of TMS-OTf can be used in place of stoichiometric amounts of TiCU in silyl ketene acetal-imine additions.When conducted at the optimal temperature of -65 C, 3-amino esters enriched in the anti diastereomer are obtained in 45-85% yields. Use so far has been limited to nonenolizable imines. Interestingly, the observed anti stereoselectivity is independent of the geometry of the silyl ketene acetal, further evidence that a nonpericyclic mechanism is involved in the Lewis acid catalyzed addition of silyl ketene acetals to imines. An applies-... 

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