Diasteroselectivity

Under thermodynamically controlled conditions, using triethylamine as base for the addition of enones to 5 and sodium methoxide in methanol as base for the addition of a,/ -unsaturated esters, the diastereomeric ratios of 6 range from 95 5 to 97 3. The excellent diasteroselectivities are retained in the Michael addition of 5 to -substituted enones and esters, however, modest synjami selectivities are found212,213. 

Bekiaris et al. have studied the reaction of fluorinated pentane-2,4-diones and phosphanes and have reported the formation of bicyclic compounds and phosphaadamantanes <1997CB1547>. Compounds 167 and 168 were formed in a diasteroselective manner (Scheme 13) and their structures were determined by single crystal X-ray structure analysis. 

Triquinphosphoranes 79 react with borane to give two diasteromeric adducts with different selectivity (Scheme 4). The diasteroselectivity is dependent on the nature and position of the substituent <19990M915>. 

Highly diasteroselective and chemoselective reductions may be performed on the hydroxy functions of (r/6-arene)-tricarbonylchromium complexes. Treatment of the chromium-complexed benzylic alcohol 29 with triethylsilane and boron trifluoride etherate in dichloromethane at —78° to 0° gives only diastereomer 30 in 75% yield (Eq. 40).181 In a similar fashion, treatment of the complexed exo-allyl-endo-benzylic alcohol 31 with an excess of Et3SiH/TFA in dichloromethane at room temperature under nitrogen produces only the endo-aflyl product 32 in 92% yield after 1.5 hours (Eq. 41). It is noteworthy that no reduction of the isolated double bond occurs.182... 

Vinylstannanes with hydroxy groups in the allylic position undergo enantioselective and diasteroselective hydrogenation in the presence of rhodium catalysts, as illustrated in reaction 19275. Vinylstannanes can be converted into /1-stannylacrylic esters in a two-step synthesis, as shown in reaction 20276. 

TABLE 4-19. Diasteroselective Hydroxylation of Chiral Carboximide Sodium Enolates Using 2-(Phenylsulfonyl)-3-Phenyl-Oxaziridine (141) in THF at — 78°C... 

The bromo-aryl groups are first linked by (5,5 )-stilbene diol to form the dibromide 33. Compound 33 is then dilithiated with t-BuLi at —78°C, followed by addition of CuCN. Intermediate 34 is presumably formed during the reaction. Reductive elimination promoted by molecular oxygen provides compound 35 at 77% yield with 93 7 diasteroselectivity. The final biaryl compound ellagi-... 

The energy profiles for an enantioselective and a diasteroselective synthesis are compared in Figure 14.2. An interesting feature of the asymmetric catalytic synthesis is the nonlinear correlation between the optical purity of the chiral catalyst or auxiliary and that of the reaction product, reported... 

Addition of the indium reagent derived from the foregoing (P)-allenylstannane to /8-benzyloxy-a-methylpropanal as the aldehyde substrate at low temperature afforded a 70 30 mixture of anti,anti and anti,syn adducts (Eq. 9.141). The improved dia-stereoselectivity in this case can be attributed to substrate control, reflecting the chelating ability of an OBn versus an ODPS group. The lower temperature may also account for the improved diasteroselectivity. 

The poor diasteroselectivity at the yS-carbon of cyclic enones arises from poor facial selectivity during cuprate addition. Acyclic enones may also give poor dia-stereoselectivity at the y8-carbon center because of E Z isomerization arising from an equilibrium between an enone-cuprate d-re complex and starting materials. Much work remains to be done in the development of asymmetric variations in a-aminoalkylcuprate chemistry. 

High levels of asymmetric induction can be achieved intramolecularly if the substrate functionality and the heteroatom ligand are contained in the same molecule. Chiral amido(a]kyl)cuprates derived from allylic carbamates [(RCH= CHCH20C(0)NR )CuR undergo intramolecular allylic rearrangements with excellent enantioselectivities (R = Me, n-Bu, Ph 82-95% ee) [216]. Similarly, chiral alkoxy(alkyl)cuprates (R OCuRLi) derived from enoates prepared from the unsaturated acids and trans-l,2-cyclohexanediol undergo intramolecular conjugate additions with excellent diasteroselectivities (90% ds) [217]. 

Cyclic ketones can also be formed by intramolecular aldol condensation. Roger C. Whitehead of the University of Manchester found (Tetrahedron Lett. 2005,46,2803) that the cis ene dione 4, available by oxidation of the corresponding furan 3, underwent highly diasteroselective aldol condensation, to give untenone A 5. 

Only tethered terminal olefins are reactive, and ring junctures are always formed by coupling to the internal carbon of the multiple bond. If an asymmetric center is present in the tether, the reaction proceeds with high diasteroselectivity. Alkenes with substituents a to the double bond favor trans product formation, whereas fi substituents lead to cis products. 

Electroenzymatic reactions are not only important in the development of ampero-metric biosensors. They can also be very valuable for organic synthesis. The enantio- and diasteroselectivity of the redox enzymes can be used effectively for the synthesis of enantiomerically pure compounds, as, for example, in the enantioselective reduction of prochiral carbonyl compounds, or in the enantio-selective, distereoselective, or enantiomer differentiating oxidation of chiral, achiral, or mes< -polyols. The introduction of hydroxy groups into aliphatic and aromatic compounds can be just as interesting. In addition, the regioselectivity of the oxidation of a certain hydroxy function in a polyol by an enzymatic oxidation can be extremely valuable, thus avoiding a sometimes complicated protection-deprotection strategy. 

In the presence of a Lewis acid or fluoride ion, imines react with allylsilane to yield the homoallylic amines with high stereoselectivity119,120. Thus, treatment of N-galactosylaldimine 81 with allylsilane in the presence of excess of SnCU yields the corresponding allylated product 82 (equation 54). It is noted that aliphatic aldimines do not react under these conditions. Fluoride ion promoted crotylation of aldimines proceeds in a regiospecific and diasteroselective manner121. A pentacoordinate silicate moiety is involved in this reaction. 

An intramolecular variant of this reaction was reported in 1988 by Molander and Kenny (Table l)37. These reactions proceeded in reasonable yields and exhibited extremely high diasteroselectivity (200 1). It was suggested that the aldehyde functionality is first reduced, allowing chelation control of the stereochemistry (e.g. 3). 

A number of intramolecular ketyl anion/olefin coupling reactions promoted by Sml2 have been reported since 1985. In general, Sml2 reactions give extremely high yields and exhibit high diasteroselectivity. 

Treatment of L-ascorbic derivative 161 with lithium iodide and methyl iodide in 1,2-dimethoxyethane gave the C-methylation product 162 with high diasteroselectivity, and similar results were found with the equivalent D-isoascorbic derivative.356... 

G. Bellucci, G. Catelani, C. Chiappe, and F. D Andrea, A simple and highly diasteroselective preparation of glycal epoxides using the MCPBA-KF complex, Tetrahedron Lett., 35 (1994) 8433-8436. 

A few years previously, the same research group reported a one-pot condensation of three components (methylphenylglyoxylate (MPG), aniline, and aromatic aldehyde), promoted by a TiCl3/pyridine system under anhydrous conditions, for the diasteroselective synthesis of P-amino-a-hydroxyesters (Equation 14.24) [32]. 

This process provides the desired products with yields up to 80% and syn-diasteroselectivity. These derivatives are of considerable importance because they are incorporated into many biologically active peptides, such as bestahn, amas-tatin, norstatin, and taxol [33]. 

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