Chiral alcohols unsaturated

The sesquiterpenoid hydrocarbons (5)-a-curcumene (59) and (5)-xanthorrhizol (60) were prepared by asymmetric conjugate addition of the appropriate aryllithium reagent to unsaturated oxazoline 56 to afford alcohols 57 (66% yield, 96% ee) and 58 (57% yield, 96% ee) upon hydrolysis and reduction. The chiral alcohols were subsequently converted to the desired natural products. ... 

A proline derived chiral nickel complex 1 may be used instead of oe,/J-unsaturated esters of lactones modified with a chiral alcohol as the Michael acceptor. The a,(9-unsaturated acid moiety in 1 reacts with various enolates to afford complexes 2 with diastereomcric ratios of 85 15 to 95 5. Hydrolysis of the imine moiety yields the optically active /(-substituted r-alanines. A typical example is shown296. 

Optically active bicyclo[2.2,2]octanes can be obtained via diastercoselective MIMIRC reaction of lithium dienolates and a,/ -unsaturated esters of various chiral alcohols. Good yields (70-90%), high endo selectivities (> 95%) and diastereomeric ratios that depend on the auxiliary alcohol are found in these additions. The highest diastereomeric ratio reached was 18 82 using a camphor derived sulfonamide. The diastereomeric ratio could be improved (up to 9 91) by titanium(IV) chloride catalyzed addition of the corresponding silylenolates with the chiral a,/J-unsaturated esters358. 

Fluoboric acid is also an efficacious promoter of cyclic oxo-carbenium ions (Scheme 4.24) bearing an activated double bond which, in the presence of open-chain and cyclic dienes, rapidly undergo a Diels-Alder reaction [91]. Chiral a, -unsaturated ketones bearing a -hydroxy substituents, protected as acetals, react with various dienes in the presence of HBF4, affording Diels-Alder adducts that were isolated as alcohols by hydrolysis of the acetal group by TsOH. Some examples of reactions with isoprene are reported in Table 4.23. The enantios-electivity of the reaction is dependent on the size of the substituent R on the of-carbon high levels of asymmetric induction were observed with R = z-Pr (90 1) and R = t-Bu (150 1) and low levels with R = Me (2.7 1) and R = Ph (3.0 1). Scheme 4.24 shows the postulated reaction mechanism. 

The introduction of various metal-catalyzed reactions, however, remarkably expanded the scope of the epoxidation of Q,.3-unsaturatcd ketones. Enders et al. have reported that a combination of diethylzinc and A-methyl-pseudoephedrine epoxidizes various o,. j-unsaturatcd ketones, under an oxygen atmosphere, with good to high enantioselectivity (Scheme 23).126 In this reaction, diethylzinc first reacts with the chiral alcohol, and the resulting ethylzinc alkoxide is converted by oxygen to an ethylperoxo-zinc species that epoxidizes the a,/3-unsaturated ketones enantioselectively. Although a stoichiometric chiral auxiliary is needed for this reaction, it can be recovered in almost quantitative yield. 

It is important to note that the Ru-catalyzed RCM and the Zr-catalyzed resolution can be carried out in a single vessel, without recourse to intermediate isolation. The unsaturated medium-ring amides 5 and 8 can be subjected to 10 mol% of the chiral Zr catalyst and EtMgCl, in the same flask, to afford unsaturated 6 and 9 in 81% and 54% isolated yield, respectively. As depicted in Eq. 1, a similar tandem diene metathesis/ethylmagnesation can be carried out on ether 10, leading to the formation of unsaturated chiral alcohol 11 in 73% yield and >99% ee. 

Several methods for the asymmetric epoxidation of electron-poor alkenes rely on the use of metal peroxides associated with chiral ligands . Enders and coworkers reported that ( )-a,/ -unsaturated ketones may be epoxidized using stoichiometric quantities of diethylzinc and a chiral alcohol, in the presence of molecular oxygen (equation 33). The best enantioselectivities were found using (/ ,/ )-Af-methylpseudoephedrine 54 as R OH... 

Asymmetric reduction of a,/l-unsaturated aldehydes with transition metal catalysts has not yet proven ready for widespread industrial application. One area, namely the chiral reduction of enals to yield chiral alcohols using bakers yeast has been... 

The conjugate addition of (achiral) nucleophiles to a,3-unsaturated esters of chiral alcohols (4) generally produces optically active 3-branched acids, (7) (ew-7) 1, after saponification of the diastereomeric ester intermediates (5) and (6 Scheme 2).6... 

Three different strategies have been envisaged. The chiral information can either be incorporated into the alkyne or linked to the heteroatom or to the a,/ -unsaturated substituent at the carbene complex carbene carbon. High diastereoselectivities (57a 57b >96 4) have been observed in reactions of vinyl carbene complex 55 with the chiral propargylic ether 56 bearing the bulky trityloxy substituent [57a]. A more general approach is based on chiral alcohols incorporated into the alkoxycarbene complex. Upon benzannulation with tert-butylethyne, the menthyloxy carbene complex 58 gave a diastereoselectivity of 10 1 in favor of the naphthalene tricarbonylchromium complex 59a [57c, 57d]. Finally, the tandem benzannulation-Mitsunobu reaction of optically active carbene complex 60 with 5-hexyn-l-ol afforded the anti-benzoxepine complex 61 as the only diastereomer (Scheme 23) [57b]. 

Marko et al. employed an enantioselective Noyori BINAL-H reduction in the synthesis of methyl monate C (11), the methyl ester derivative of the potent antibiotic pseudomonic acid C6 (Scheme 4.3e). The a,(3-unsaturated ketone 12 underwent the Noyori reduction with the (S)-BINAL-H reagent to give the product desired (13) in 70% yield and 95% ee. The chiral alcohol was then condensed... 

With the exception of the diol 9, that was obtained from the corresponding aldehyde in up to 35% yield, most of the chiral diols mentioned above were isolated in yields of only 20-25%. The formation of the acyloin-type condensation products is in competition with the much more efficient reduction of the carbonyl carbon and saturation of the double bond of the unsaturated aldehydes that were used as substrates. We became interested in the mode of reduction of particular aldehydes such as 54-56 (Scheme 8) in a study of the total synthesis of natural a-tocopherol (vitamin E) (23). We expected to obtain chiral alcohols that would be useful for conversion into natural isoprenoids from the reduction of the a-double bond of the above aldehydes. Indeed, 54-56 afforded up to 75% yield of the saturated carbinols 57-59 by treatment with yeast. Whereas the ee of 57 and 58 was ca 85%-90%, that of 59 is 99%, as shown by NMR experiments on the (-)-MTPA derivative (24). The synthetic significance of carbinol 59 was based on the structural unit present in natural isoprenoids (see brackets in structural formulas). This protected synthon can be unmasked by ozonolysis, as indicated by the high yield conversion of 59 into (S)-(-) -3-methyl-y-butyrolactone 60 (Scheme 9). Product 59 is a bifunctional chiral intermediate which does not need protective manipulation in that... 

Dehydrogenative oxidation of secondary alcohols in the presence of acetone is the reverse process of transfer hydrogenation of ketones with 2-propanol [87b, 95b]. Kinetic resolution of racemic secondary alcohols is possible using this process with an appropriate chiral catalyst and suitable reaction conditions. As exemplified in Scheme 45, a variety of racemic aromatic or unsaturated alcohols can be effectively resolved in acetone with a diamine-based Ru(II) complex 42 or 50 [129]. Chiral alcohols with an excellent optical purity are recovered at about... 

The first approach to this problem was to attach the chiral auxiliary to the diene by a vinylogous trans-esterification reaction of chiral alcohols with the 3-alkoxy enones (Scheme 21). This reaction was used to construct a variety of chiral dienes including the menthol and phenmenthol dienes (55a) and (55b) by transesterification followed by enol silylation using the Simchen procedure (RsSiOTf taN). However, these dienes exhibit poor diastereofacial selectivity despite the precedent for high stereochemical control in homo Diels-Alder reactions by the use of similar auxiliaries on a,P-unsaturated enones. ... 

JV-Phenyl- or A-methyl-C-phenyl nitrones with (/ )-4-vinylsulfmyltoluene react with complete stereoselection in a process involving only the. Si-face of the alkene88. Cycloaddition of 4,5-dihydro-3//-pyrrole 1-oxide to unsaturated esters of chiral alcohols derived from camphor occurs with poor enantiofacial selection on the nitrone, but high diastereofacial preference on the alkene89. 

Table 4.9. Asymmetric 1,4-addition to unsaturated esters of chiral alcohols. Numbers in the OR column refer to Figure 4.21.

A recent investigation of a second Pseudodistoma species from Algoa Bay nearly 200 kms to the east of the Tsitsikamma Marine Reserve, collected as part of a large collaborative marine invertebrate and algal survey of the warm temperate coast of southern Africa by Rhodes University, the Coral Reef Research Foundation and the NCI, also yielded bioactive acyclic amines, pseudodistamine (84), two unsaturated amines (85 and 86) and the quaternary N-methylated (3-carbolinium alkaloid (87) [83], Standard spectroscopic data were used to elaborate the structures of these compounds with Mosher s method providing the absolute stereochemistry of the chiral alcohol functionality in 84. Oxidative... 

Full details have been given for the synthesis of a variety of a-diazo-esters (113) and of chiral oc-thio-esters (114). a,8-Epoxy-esters (115) can be obtained from the parent unsaturated esters either by using a new epoxidation reagent prepared from fluorine gas and aqueous acetonitrile or lithium t-butylhydroperoxide ( ). When this latter reagent is added to unsaturated esters derived from chiral alcohols, reasonable diastereoselection is observed but, as yet, not enough (up to 60%) to rival the Sharpless method. All four isomers of the useful epoxy-esters [(116) (2R,3S) isomer] have been obtained from the... 

---