Desymmetrization Diene

The epoxidation of divinyl carbinol constitutes a special case of a dienol epoxida-tion, as the starting diene is not conjugated (Scheme 9.10). Desymmetrization by SAE, followed by a Payne rearrangement, furnishes the vinylepoxide in high yield and with excellent enantioselectivity (compare Table 9.2, Entry 1) [43]. 

A structural requirement for the asymmetric Birch reduction-alkylation is that a substituent must be present at C(2) of the benzoyl moiety to desymmetrize the developing cyclohexa-1,4-diene ring (Scheme 4). However, for certain synthetic applications, it would be desirable to utilize benzoic acid itself. The chemistry of chiral benzamide 12 (X = SiMes) was investigated to provide access to non-racemic 4,4-disubstituted cyclohex-2-en-l-ones 33 (Scheme 8). 9 Alkylation of the enolate obtained from the Birch reduction of 12 (X = SiMes) gave cyclohexa-1,4-dienes 32a-d with diastereoselectivities greater than 100 1 These dienes were efficiently converted in three steps to the chiral cyclohexenones 33a-d. 

Landais has extended his desymmetrization of dienes from dihydroxylation approaches to a cyclopropanation reaction. A Cu-pybox complex provides the highest enantioselectivities and good diastereoselectivity in the asymmetric cyclopropanation of the silyl-substituted cyclopentadiene 210 ... 

Jeong described desymmetrization of dienynes, such as iV-propargyl-jY-(penta-l,4-dien-3-yl) tosylamides, by the asymmetric Ir(i)-based PK-type reaction. The corresponding vinyl-substituted bicyclo[3,3,0]-octenones were obtained with high diastereoselectivity and enantioselectivity (Equation (36)). ... 

Desymmetrization of an achiral, symmetrical molecule through a catalytic process is a potentially powerful but relatively unexplored concept for asymmetric synthesis. Whereas the ability of enzymes to differentiate enantiotopic functional groups is well-known [27], little has been explored on a similar ability of non-enzymatic catalysts, particularly for C-C bond-forming processes. The asymmetric desymmetrization through the catalytic glyoxylate-ene reaction of prochiral ene substrates with planar symmetry provides an efficient access to remote [28] and internal [29] asymmetric induction (Scheme 8C.10) [30]. The (2/ ,5S)-s> i-product is obtained with >99% ee and >99% diastereoselectivity. The diene thus obtained can be transformed to a more functionalized compound in a regioselective and diastereoselective manner. 

A desymmetrization of cyclohexa-2,5-dienes (22) and (24), obtained by Birch reductive alkylation, through a diastereoselective intramolecular hydroamination led with high selectivity to the corresponding bicyclic allylic amines (23) and (25) (Scheme 6).19... 

Enantioselective RCM is achieved using the chiral Mo complex 79 [30]. Kinetic resolution occurred in the reaction of the racemic diene 80 catalysed by 79, and the cyclized product 81 with 93% ee was obtained, and the unreacted diene 80 (19%) of 99% ee was recovered. Also the optically active dihydrofuran 83 with 93% ee was obtained in 85% yield by enantioselective desymmetrization through RCM of triene 82 using the Mo complex 79 [30a]. 

Trisubstituted cyclic alkenes have been kinetically resolved via a chiral dioxirane (4), generated in situ from the ketone and Oxone. A sequential desymmetrization and kinetic resolution of cyclohexa-1,4-dienes has also been achieved. The observed stereochemical results have been rationalized on the basis of a spiro-planar transition state model.93... 

The desymmetrization of 4-substituted-4-(3-formylpropyl)cyclohexa-2,5-dien-l-one 65 formed - in a single step - three contiguous stereocenters, including a quaternary stereocenter (Scheme 2.56). 

A double iodoetherification of C2-symmetric acetals has been used for the desymmetrization of 1,6-dienes in an asymmetric total synthesis of rubrenolide (Equation 78) <2005AGE734>. Remarkably, four stereogenic centers have been installed in one reaction step. Stereoelectronic effects in the diastereoselective synthesis of 2,3,5-trisubstituted tetrahydrofurans via iodoetherification have been studied in detail, and I(2,4,6-collidine)2C104 proved to be an efficient reagent for highly stereoselective iodoetherifications <20010L429>. 

Permanganate oxidation of 1,5-dienes to prepare f r-2,5-disubstituted tetrahydrofurans is a well-known procedure (Equation 80). The introduction of asymmetric oxidation methodology has revived interest in this area. Sharpless-Katsuki epoxidation has found widespread application in the catalytic enantioselective synthesis of optically active tetrahydrofurans and the desymmetrization of w ro-tetrahydrofurans <2001COR663>. A general stereoselective route for the synthesis of f-tetrahydrofurans from 1,5-dienes has been developed which uses catalytic amounts of osmium tetroxide and trimethyl amine oxide as a stoichiometric oxidant in the presence of camphorsulfonic acid <2003AGE948>. 

The asymmetric glyoxylate-ene reactions have been exploited in the total synthesis of (—)-specionin, which involves asymmetric desymmetrization of a prochiral diene (eq 3), and (—)-xylomollin, which involves an efficient kinetic resolution of a racemic diene (eq4).i - ... 

Katsuki-Sharpless desymmetrization of penta-l,4-dien-3-ol gives the monoepoxide 490, which can be converted into l,4-dideoxy-l,4-imino-D-lyxitol 491 (Scheme 13.112) [217]. 

Related to a resolution, a desymmetrization reaction was used in an approach to Uvaricin. Use of AD-mix [1 gave only moderate diastereoselection with 21, but the use of (DHQD)2AQN gave 22 after two cycles the first reaction was run to 50% completion and the recycled diene 21 was then subjected to the reaction conditions for a second time (Scheme 3.17) [320]. 

Burke and Jiang reported that the palladium-catalyzed diastereoselective double allylation of the diol bis(allylic acetate) 613 using (R,R) DPPBA 607 afforded the bis-tetrahydrofuran core 614 in 97% yield (Scheme 187).265 The resulting diene 614 was further transformed into a known intermediate 615 for the synthesis of uvaricin. They demonstrated that palladium (0)-catalyzed desymmetrization of the C2 diol 616 with Trost s ligand 607 afforded the tetrahy-drofuran 617 diastereoselectively (Scheme 188).266 The product 617 was manipulated to the F ring of halichondrin B (618). 

Elimination in some cyclic systems proceeds regio- and stereoselectively. The Pd-catalyzed reaction of the racemic carbonate 491 afforded the diene 492 with 86 % ee via desymmetrization of the 7r-allylpalladium intermediate 493 when (-)-TolBINAP was used as a ligand [190],... 

Later, the groups of Sakai and of Tanaka and Suemune, respectively, extended the scope of the enantioselective cyclizations by employing desymmetrization of the aldehyde substrates bearing two identical terminal olefin moieties, and the cyclopentanone products with two vicinal stereo-centers, 8 or 9, could be obtained using a catalytic amount of the cationic Rh complex (5 mol%) (Table 8.2). However, if neutral Rh catalysts were employed, a high catalyst loading at 50 mol% was needed (entries 1, 2). Tanaka, Suemune, and co orkers also developed the kinetic resolution of unsymmetrical racemic diene-aldehyde 10 via a Rh-catalyzed asymmetric hydroacylation reaction (Scheme 8.5). The cyclization product could be obtained in >95% ee. ... 

Desymmetrization of Achiral Dienes via Cataiytic Asymmetric Hydrosilylation... 

Desymmetrization of dienes by cataiytic asymmetric hydrosilylation. Oxidation of the product provides a valuable 1,3-diol. 

One valuable application of desymmetrization processes is the formation of quaternary stereocenters. In this case, a fully substituted carbon that lies in the plane of symmetry of the reactant becomes a stereocenter by reaction at one of the two substituents. This type of desymmetrization in the context of olefin metathesis is shown in Equation 21.14. In this example, the achiral, symmetric triene is converted to the chiral, non-racemic diene with 87% ee. 

The experimental enthalpy of activation for disrotatory thermal isomerization of cis-l,3,5-hexatriene to 1,3-cyclohexadiene in the gas phase at 100 C is 29.2 kcal/mol [13]. The reaction is exothermic by 14.5 kcal/mol [14, p. 127], so of the reverse reaction is 43.7 kcal/mol, but - in spite of its high activation energy - it is characterized as allowed by all of the common orbital symmetry criteria. In norcaradiene ([4.1.0]hepta-2,4-diene), the cyclopropane ring bridging Cl and Ce of cyclohexadiene has built the disrotation into the molecule, desymmetrizing it - and its monocyclic isomer, cycloheptatriene - to C, in which the 61 and ai orbitals correlate directly (Fig. 5.3). The rate of isomerization is so much faster that it had to be measured at low temperature (ca. 100 K) in a hydrocarbon glass [15] is only 6.3 kcal/mol ... 

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