2- 2- ,3-diene, optically pure

Danishefsky et al. were probably the first to observe that lanthanide complexes can catalyze the cycloaddition reaction of aldehydes with activated dienes [24]. The reaction of benzaldehyde la with activated conjugated dienes such as 2d was found to be catalyzed by Eu(hfc)3 16 giving up to 58% ee (Scheme 4.16). The ee of the cycloaddition products for other substrates was in the range 20-40% with 1 mol% loading of 16. Catalyst 16 has also been used for diastereoselective cycloaddition reactions using chiral 0-menthoxy-activated dienes derived from (-)-menthol, giving up to 84% de [24b,c] it has also been used for the synthesis of optically pure saccharides. 

The reaction of 1-thiabuta-1,3-dienes with di-(-)-menthyl fumarate exhibits high endo-selectivity when carried out thermally or when catalysed by Lewis acids. In both cases, the preferred product is the 3,4-cis-dihydrothiopyran (23) which is a source of optically pure diols <96JCS(P1)1897>. 

As the examples in Scheme 2 illustrate, the emergence of catalytic RCM proved instrumental in rendering the Zr-catalyzed C-C bond-forming reaction a more viable method in asymmetric synthesis [5d]. Catalytic RCM of dienes 4 and 7, effected by 2 mol% of Ru catalyst la, leads to the formation of 5 and 8 in high yield. Subsequent Zr-catalyzed alkylation of the resulting heterocycles in the presence of 10 mol% 3b delivers unsaturated amides 6 and 9 in the optically pure form (>98% ee) and in 76% and 77% isolated yield, respectively (Scheme 2). 

A variety of dienes have been subjected to Diels-Alder reactions with (iS)-17 and (R)-28, giving almost pure single adducts in each case. Oxidative removal of the chiral auxiliary from the adduct provides the desired optically pure building blocks 23, 26, and 30. Subsequent conversions complete the synthesis of the desired natural products 5, 27, and 32 (Scheme 5-7).7... 

As the representative examples in Scheme 6.11 illustrate, similar stragies may be applied to the corresponding alkenyl ethers (vs. styrenyl ethers) [26], The Zr-catalyzed kinetic resolution/Ru-catalyzed metathesis protocol thus delivers optically pure 2-substituted di-hydrofurans that cannot be accessed by resolution of the five-membered ring heterocycles (see Scheme 6.8). It should be noted, however, that the efficiency of the Zr-catalyzed resolution is strongly dependent, and not in a predictable manner, not only on the presence but the substitution of the acyclic alkene site of the diene substrate. The examples shown in Scheme 6.11 clearly illustrate this issue. 

The microwave synthesis of optically pure imines for subsequent diastereoselective boronate reduction at room temperature has been described50. The reduction of (1-azabuta-l,3-diene)tricarbonyliron(0) complexes and their free ligands using sodium... 

Optically pure c/.v-2-azetidi none-tethered dienes have been reported to undergo intermolecular Diels-Alder reaction with a variety of symmetric and unsymmetric dienophiles [257] providing a synthetic entry to various types of racemic and homochiral 1,3,4-trisubstituted 2-azetidinones (I, Fig. 7). 

Ring closing metathesis mediated by Grubbs II catalyst in a type c ring construction process has been used to access stereoisomeric 1,2-disubstituted tetrahydroazepine-3-ol derivatives preparation of the required diene precursor started from an optically pure substituted aziridine carboxylate ester <2007T3321>. 

Complexes of unsymmetrically substituted conjugated dienes are chiral. Racemic planar chiral complexes are separated into their enantiomers 84 and 85 by chiral HPLC on commercially available /f-cyclodextrin columns and used for enantioseletive synthesis [25]. Kinetic resolution was observed during the reaction of the meso-type complex 86 with the optically pure allylboronate 87 [26], The (2R) isomer reacted much faster with 87 to give the diastereomer 88 with 98% ee. The complex 88 was converted to 89 by the reaction of meldrum acid. Stereoselective Michael addition of vinylmagnesium bromide to 89 from the opposite side of the coordinated Fe afforded 90, which was converted to 91 by acetylation of the 8-OH group and displacement with EtjAl. Finally, asymmetric synthesis of the partial structure 92 of ikarugamycin was achieved [27],... 

As an example of conversion of complex 111 to 113, optically pure complex 126 was used for the enantioselective total synthesis of shikimic acid (129) [30]. The hydroxy-substituted diene complex 127 was prepared from 126. Silylation and decomplexation of 127 gave 128. Stereoselective dihydroxylation of the more reactive double bond of the decomplexed silyl ether derivative 128, followed by desilylation afforded (—)-methyl shikimate (129). 

Optically pure (f )-binaphthylic dienes (63) are electrochemically oxidized to 1,4-dications (64) with the -configuration.190 Since the dications can be electro-... 

The thermal asymmetric hDA (AHDA) reaction between 2,4-diaryl-l-thiabuta-l,3-dienes and di-(—)-menthyl fumarate proceeds in excellent yield to afford a mixture of four diastereomers with only moderate Jt-facial diastereo-selectivity (Equation 126). The reaction is accelerated by Lewis acids without influencing the endo selectivity, although overall yields are lower. Chromatographic separation of the cis and trans adducts followed by recrystallization enabled the diastereomers to be obtained in a stereochemically pure state. Removal of the chiral auxiliary by reaction with LiAlH4 from both cis adducts gave the enantiomers of various 2,3-bis(hydroxymethyl)-3,4-dihydro-277-thiopyr-ans and desulfurization provides a route to optically pure diols < 1996J(P1) 1897 >. 

Reactions of optically pure sulfinyl enones with acyclic dienes have never been reported, perhaps as a result of the discouraging results obtained from racemic substrates [56]. The reaction of a-phenylsulfinyl a,/i-unsaturated ketones with butadiene and 2,3-dimethyl butadiene, under Lewis acid catalysis, yielded the cyclohexadienes resulting from spontaneous elimination of sulfenic acid (precluding any conclusion about the stereoselectivity of the reaction). Analogous results were found by Nishio et al. [57] from reactions of /i-phenylsulfinyl a,/l-unsaturated ketones with acyclic dienes. The bicyclic adducts derived from cyclopentadiene are more stable [57]. In this case, the reactions gave only the exo-sulfinyl adduct,but these stereochemical results were neither confirmed nor discussed in the paper. 

The fact that these adducts were diastereoisomerically pure (deduced from the reported melting points and NMR spectra) suggests that these reactions took place with a complete control of the diastereoselectivity. Bearing this in mind, in 1989 Waldner [64] synthesized optically pure sulfoxide 55 (by MCPBA oxidation of the corresponding chiral thioether and further separation from the epimeric mixture so obtained) and studied its reactions with dienes and aza-dienes (Scheme 29). A high 7r-facial selectivity (almost complete with cyclopen-tadiene and azadienes) was observed in all cases, the approach of the diene from the dienophilic face supporting the lone pair of electrons at sulfur being favored. In the case of the reaction with cyclopentadiene, the endo-selectivity was complete as well. 

More interesting were the results obtained in reactions of 99 with acyclic dienes catalyzed by Eu(fod)3 (-20°C) and TiCl4 (-78°C). The resulting adducts 100 are unstable and underwent spontaneous sulfinyl elimination at room temperature, affording cyclohexadienes. Reactions with dienes lacking substituents at C-1 (butadiene, 2-methyl butadiene and 2,3-dimethyl butadiene) yielded optically pure compounds 101 (Scheme 49). These results indicate that the regio-selectivity and the 7r-facial selectivity of the cycloadditions are complete (only one adduct is formed) under both catalytic conditions. Desulfinylation of 100 is also completely regioselective. 

These results were explained by assuming the exclusive formation of the exo-102 adduct in reactions conducted under TiCl4 catalysis, which can undergo transformation into optically pure cyclohexadienes 103 and 104 (Scheme 51). The endo/exo selectivity of reactions catalyzed by Eu(fod)3 must be lower (as shown in reactions with cyclic dienes, see Scheme 48), and results in the formation of two adducts, endo-102 and exo-102. The former can undergo transfor-... 

Clever entries to enantiopure carbapyranoses exploited optically pure or meso cw-diene diols easily obtained from aromatic compounds by... 

Similar diastereoselectivity is observed in reaetions of 1 with aeyclic dienes. Thus reaction with butadiene catalyzed by ZnCL results in the single adduct 3. which was converted into the optically pure alcohol 4 by oxidative removal of the chiral auxiliary group.-... 

Unsymmetrically substituted diene iron tricarbonyl complexes are formed as racemic mixtures of compounds having planar chirality. Optically pure diene iron tricarbonyl complexes can been prepared by classical chromatographic separation of diastereomeric mixtures of a-methylbenzylamine and ephedrine salts, and of semioxa-mazones and oxazohdines derivatives. Direct asyimnetric complexation to cychc dienes can be achieved 73% ee using iron pentacarbonyl in the presence of a chiral l-aza-1,3-butadiene. 

A number of the reactions discussed above were used in a synthetic sequence. Friedel Crafts acylation of (98) gives (99) after isomerization of the diene geometry using sodium methoxide. Bromination of aTMS-enol ether, formed from (99), with DBA was nonstereospecific however, the isomers were readily separated (Scheme 159). The pure a-bromoketone is stereospecificaUy methylated and transformed into an epoxide. Lewis acid mediated isomerization of the epoxide affords an optically pure ketone (100). 

The utilization of an optically active triazolinedione for asymmetric transfer has also led to the preparation of enantiomerically pure polycyclic hydrocarbons. The method provides a straightforward means for introducing optical activity into chiral propellanes that possess a conjugated diene unit. Racemic propellane reacts with (-)-enethyl acetate at —78 °C to give, after HPLC separation, the two optically pure urazoles. Subsequent reduction with lithium aluminum hydride affords the two propellanes in enantiomerically pure form (eq 3). 

Thus optically pure shikimic acid (347) has been synthesized via the addition of 1,4-diacetoxybuta-diene (345) to (340a), whereas the Diels-Alder reaction of )V-dienylcarbamate (348) to hydroxy enone (340b) served as the key step for a synthesis of the enantiomer (350) of naturally occurring pumiliotoxin C (142) (c/. Scheme 35). 

Optically pure menthyloxybutyrolactone (421) was obtained by crystallizing a mixture of both epimers (420) (prepared fiom racemic 419) under equilibrating conditions. Cycloadditions of dienes occurred at 110-120 C exclusively to the much less hindered bottom face of (421) with >97% endo selectivity to give adducts (423) (Scheme 101, Table 28). ... 

The Brpnsted acid-assisted chiral Lewis acid (BLA) 28, prepared from a 1 2 molar ratio mixture of a trialkylborate and optically pure binaphthol, is also an excellent chiral promoter for the aza Diels-Alder reaction of imines with Danishefsky dienes (Eqs 44 and 45). Enantioselectivity and double diastereodifferentiation in reactions employing chiral 28 are slightly better than those using chiral 27 [41]. 

Diels-Alder reactions of enantiomerically enriched 2H-azirine 3-phosphon-ates (281), a new class of chiral iminodienophiles, and dienes stereoselectively furnish optically pure, bicyclic aziridine adducts (282). Hydrogenation of (282) results in a ring opening that affords the first examples of optically pure quaternary piperidine phosphonates. Two step synthesis of an enantiomeric pure cyclic phosphite (283) and its application as a chiral phosphorus nucleophile in the asymmetric Michael addition to nitroalkenes (284) provides an efficient... 

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