Optical yield

Asymmetric cyclization using chiral ligands has been studied. After early attempts[142-144], satisfactory optical yields have been obtained. The hexahy-dropyrrolo[2,3-6]indole 176 has been constructed by the intramolecular Heck reaction and hydroaryiation[145]. The asymmetric cyclization of the enamide 174 using (S j-BINAP affords predominantly (98 2) the ( )-enoxysilane stereoisomer of the oxindole product, hydrolysis of which provides the ( l-oxindole aldehyde 175 in 84% yield and 95% ec. and total synthesis of (-)-physostig-mine (176) has been achieved[146]. 

High enantioselectivities and regioselectivities have been obtained using both mono- and 1,2-disubstituted prochinal olefins employing chiral phosphine phosphite (33,34) modified rhodium catalysts. For example, i7j -2-butene ia the presence of rhodium and (12) (33) gave (3)-2-meth5ibutanal ia an optical yield of 82% at a turnover number of 9.84. ... 

Enantioselective addition of hydrogen cyanide to hydroxypivaldehyde (25), catalyzed by (lf)-oxynittilase, afforded (R)-cyanohydrin (26) in good optical yield. Acid-catalyzed hydrolysis followed by cyclization resulted in (R)-pantolactone in 98% ee and 95% yield after one recrystallization (56). 

Substitution, All lation, and Rearrangement. The reaction of alkaline phenoxides with alkyl 3 -2-(chloro)- or 3 -2-(mesyloxy)propionate gives optically active R-2-aryloxyaIkanoic acid esters in good chemical and optical yields (>97% ee) (51—53) ... 

Aziridines have been prepared stereospecifically by the nucleophilic addition of the nitrogen residue to alkenes <80T73). Introduction of the nitrene is accomplished readily via a Michael-type addition with free diphenylsulfilimine (Scheme 12), and where a chiral sulfilimine is used the chirality is transferred to the aziridine with optical yields in excess of 25%. 

J -Dehydroquinolizidine reacts with the enantiomeric (—)- and (-l-)-menthyl chloroformates forming (—)- and (-l-)-menthoxycarbonyl- -dehydroquinolizidines. These can be reduced as such or in the form of their immonium salts with sodium borohydride to (—)- and (+)-l-menthoxy-carbonylquinolizidines, which give (+)- and (-)-lupinin, respectively, on reduction with lithium aluminum hydride (243). The optical yield of the asymmetric reduction is about 10%. 

Less reactive dienes such as cyclohexadiene can be employed efficiently, giving the adduct in 90% yield in 93% ee. Acyclic dienes such as piperylene, 2,4-hexadiene, and 1-phenylbutadiene also react with the acryloyloxazolidinone derivative to afford Diels-Alder cycloadducts in high optical yields (Scheme 1.38, Table 1.17). 

Although furan is usually a poor diene in the Diels-Alder reaction, the chiral copper reagent 24b promotes its asymmetric addition to acryloyloxazolidinone to afford the 7-oxabicyclo[2.2.1]hept-2-ene derivative in high optical purity (Scheme 1.40). Because a retro-Diels-Alder reaction occurs above -20 °C, the reaction must be performed at low temperature (-78 °C) to obtain a high optical yield. The bicy-... 

Collins and coworkers applied the bis(tetrahydroindenyl)zirconium triflate 32, which is used as a polymerization catalyst, to the asymmetric Diels-Alder reaction [50] (Scheme 1.61). A remarkable solvent effect was observed - although only a low optical yield was obtained in CH2CI2, high optical purity (91% ee) was realized in 2-nitropropane by use of only 1 mol% of the catalyst. The catalyst is also effective for crotonoyloxazolidinone, giving the cycloadduct in 90% ee. 

Stereoselectivity may be influenced strongly by both temperature and pressure. In general, the optical yield is decreased with increasing pressure, and at high pressures (50atm) the predominant product chirality actually has been... 

Optically active hydroperoxides 244 were found285 to oxidize prochiral sulphides into the corresponding sulphoxides in higher optical yields (up to 27%) in comparison with those observed with peracids (equation 132). Moreover, the optical purity of the sulphoxides formed may be enhanced by addition of Ti(OPr-i)4. The oxidation of racemic 2-methyl-2,3-dihydrobenzothiophene 246 with these peroxides gave a mixture of cis and trans-sulphoxides 247 (equation 133). In all cases of the oxidation with the hydroperoxide alone the formation of the trans-isomer was strongly preferred and the e.e. value (up to 42%) of the cis-isomer was always higher than that of the trans-isomer. Moreover, the addition of Ti(OPr-i)4 furthermore promoted the selective formation of the frans-sulphoxide 247 and remarkably enhanced the e.e. value of both isomers. 

A closely related asymmetric synthesis of chiral sulphoxides, which involves a direct oxidation of the parent sulphides by t-butylhydroperoxide in the presence of metal catalyst and diethyl tartrate, was also reported by Modena and Di Furia and their coworkers-28-7,288 jjje effect 0f the reaction parameters such as metal catalyst, chiral tartrate and solvent on the optical yield does not follow a simple pattern. Generally, the highest optical purities (up to 88%) were observed when reactions were carried out using Ti(OPr-i)4 as a metal catalyst in 1,2-dichloroethane. 

However, (—)-(S)-p-tolylthio-(p-tolyl) sulphinylmethane 252 was obtained in 20% e.e. from gem-disulphide 253 using Helmintosporium cultures306 (equation 138). With this culture much higher asymmetric induction was observed when 1,3-dithianes 254 substituted or unsubstituted at carbon 2 were used as substrates (equation 139). Whereas the optical yield of the (— )-(S)-monosulphoxide 255 (X = Y = H) was about 14% only, this... 

A very interesting approach to optically active sulphoxides, based on a kinetic resolution in a Pummerer-type reaction with optically active a-phenylbutyric acid chloride 269 in the presence of /V,A -dimethyIaniline, was reported by Juge and Kagan332 (equation 149). In contrast to the asymmetric reductions discussed above, this procedure afforded the recovered sulphoxides in optical yields up to 70%. Chiral a, /1-unsaturated sulphoxides 270 were prepared via a kinetic resolution elaborated by Marchese and coworkers333. They found that elimination of HX from racemic /i-halogenosulphoxides 271 in the presence of chiral tertiary amines takes place in an asymmetric way leading to both sulphoxides 270 and 271, which are optically active (optical yields up to 20%) with opposite configurations at sulphur (equation 150). 

The preparation of enantiomerically enriched a-ketosulphoxides 272 was also based on a kinetic resolution involving the reaction of the carbanion 273 derived from racemic aryl methyl sulphoxides with a deficiency of optically active carboxylic esters 274334, (equation 151). The degree of stereoselectivity in this reaction is strongly dependent on the nature of both the group R and the chiral residue R in 274. Thus, the a-ketosulphoxide formed in the reaction with menthyl esters had an optical yield of 1.3% for R = Et. In the... 

Abbott and coworkers229 found that nucleophilic addition of amines to a, p-unsaturated sulfoxide gave asymmetrically induced adducts. For example, treatment of (R)-(—)-cis-propenyl p-tolyl sulfoxide 184 with piperidine in methanol gave a quantitative mixture of the diastereomeric adduct 185. Reduction of this mixture gave (Rs)-(Sc)-2-piperidinopropyl p-tolyl sulfide 186 in 74% optical yield, suggesting that the amines attack from the opposite side of the bulky aryl group at the transition state, as shown above (Figure 6). 

The plot of the optical yield, Gcmax, of the eso] when plotted vs. the DMSO molar fraction has a broad minimum between 0.43 and 0.93 mole fraction DMSO. It is unlikely that the minimum in G ma). arises from a minimum in smal alone (especially as AIT was found to be nearly constant over the full range) and it seems more reasonable that the main reason is a minimum in the radiation yield, G. Cooper and coworkers30 suggested that the minimum in G(esol ) is the result of a decreased fraction of the free electron which become solvated. 

In aqueous pyridine solution, most diaryl sulphoxides may be oxidized to the corresponding sulphones with (dichloroiodo)benzene in reasonable yields103. The reaction involves nucleophilic attack by the sulphoxide on the electrophilic chlorine-containing species, yielding an intermediate chlorosulphonium ion which then reacts with water producing the sulphone. If the sulphoxide is optically active, then an optically active sulphone is produced in excellent optical yield when the reaction is carried out in oxygen-18 labelled water104, as indicated in equation (33). 

It was found that the signs of rotation of the recovered a-phenylbutyric acid corresponded to the known absolute configurations of the deuteriated alcohols if and only if the size relationships CH3 > CD 3 and H>D were valid. In the case of (-t-)-(S)-2-propanol-l,l,l-d3 (4), the optical yield was between 0-4 and 0 5% (Horeau et al., 1965), corresponding to A AG value of about 23 cal mol at 25°C. For the primary alcohols, quite analogous results were obtained (Horeau and Nouaille, 1966). 

Table 4). Chemical and optical yields were highly dependent on the mode of fabrication of the polymer layers Enantiometric excess values, chemical... 

The results cited in this section indeed appear very promising and encouraging, but there are still many problems to solve. Chemical and optical yields are extremely sensitive to experimental conditions such as current density and electrolyte composition Some experimental details in the asymmetric reduction of citraconic acid are indeed puzzling, such as a temperature maximum of the optical yield, and the fact the same product enantiomer is formed regardless if D or l polyvaline was used... 

As seen in Table 1, (S)-4 are obtained in excellent chemical and optical yields by using the neutral and mild key reaction, the bromolactonization, followed by simple treatment with HCl. 

In view of the absolute configuration and their optical yields (88-96 %), it follows that the precursor of the (S)-4 should be 2a, which are formed highly diastereoselectively. It is likely that the predominant formation of 2a conforms to the mechanism of the bromolactonization, the S-trans transition state (ref. 3). 

In the case of the ketone (12), a racemic mixture was converted to an optically active mixture (optical yield 46%) by treatment with the chiral base (13). This happened beeause 13 reacted with one enantiomer of 12 faster than with the other (an example of kinetic resolution). The enolate (14) must remain coordinated with the chiral amine, and it is the amine that reprotonates 14, not an added proton donor. 

---