Dihydroxylation dimerization

Fig. 12.1. Predictive model for enantioselective dihydroxylation by dimeric alkaloid catalysts. (DHQD)2 catalysts give (3-approach (DHQ)2 catalysts give ot-approach. Reproduced from J. Org. Chem., 57, 2768 (1992), by permission of the American Chemical Society.

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

Tetrabutylammonium fluoride, 286 Titanium(IV) chloride-Diethylalumi-num chloride, 309 Vinylene carbonate, 342 Dihydroxylation (see Addition reactions to carbon-carbon multiple bonds) Dimerization (see Coupling reactions) Displacement reactions (see Substitution reactions)... 

The development of polymeric cinchona-derived PTCs was triggered by the group of Jew and Park in 2001 [8]. The group paid particular attention to the fact that the cinchona alkaloids have demonstrated great utility in the Sharpless asymmetric dihydroxylation. Especially, it was noted that the significant improvements in both stereoselectivity and scope of the asymmetric dihydroxylation were achieved when the dimeric ligands of two independent cinchona alkaloid units attached to heterocyclic spacers were used, such as (DHQ)2-PHAL or (DHQD)2-PYR (Figure 4.4) [9]. 

Figure 4.4 Dimerization effects in Sharpless asymmetric dihydroxylation.

The highest enantioselectivity (up to >99%) yet achieved in the addition of S-nucleophiles to enones was reported in 2002 by Deng et al. [59]. By systematic screening of monomeric and dimeric cinchona alkaloid derivatives they identified the dihydroquinidine-pyrimidine conjugate (DHQD PYR (72, Scheme 4.35) as the most effective catalyst. This material is frequently used in the Sharpless asymmetric dihydroxylation and is commercially available. Screening of several aromatic thiols resulted in the identification of 2-thionaphthol as the nucleophile giving best yields and enantioselectivity. Examples for the (DHQD PYR-catalyzed addition of 2-thionaphthol to enones are summarized in Scheme 4.35. 

Deng et al. later found that dimeric cinchona alkaloids such as (DHQ AQN (8, Scheme 6.6) and (DHQD PHAL (9, Scheme 6.7) - both well known as ligands in the Sharpless asymmetric dihydroxylation and commercially available - also catalyze the highly enantioselective cyanosilylation of acetal ketones with TMSCN... 

Elaboration of C-allyl glucose 330 to diene ester 366 by the four steps shown followed by a dihydroxylation-reduction sequence affords a mixture of the lactols 367-370 (represented in acyclic forms) having the D/L-galacto and the D/L-ido configurations in a 5 1 ratio. Hydrogenolysis provides the corresponding C-dimers 371-374, four out of the sixteen possible diastereomers. 

Jew and Park have also utilized the dimerization effect, as observed in the development of Sharpless asymmetric dihydroxylation, where ligands with two independent cinchona alkaloid units attached to heterocyclic spacers led to a considerable increase in both the enantioselectivity and scope of the substrates, to design dimeric and trimeric cinchona alkaloid-derived phase-transfer catalysts 12 [12] and 13 [13]. These authors investigated the ideal aromatic spacer for optimal dimeric catalysts, and found that the catalyst 14 with a 2,7-bis(bromomethyl) naphthalene spacer and two cinchona alkaloid units exhibited remarkable catalytic and chiral efficiency (Scheme 11.3) [14]. 

The enantioselectivity of the dihydroxylation reaction improved dramatically when the second generation ligands (dimeric ligands) were developed [ 11,12]. The best known examples, shown in Fig. 4, are the bis(dihydroquini-dinyl)phthalazine [(DHQD)2PHAL] and the bis(dihydroquinidine)pyridazine... 

Three syntheses of boronolide (38) have appeared. The first synthesis from an acrolein dimer, afforded the racemate (52). Naturally occurring (+)-boronolide has been obtained from D-glucose (53) and employing the Sharpless catalytic asymmetric dihydroxylation reaction (54),... 

Dimerization Reaction. A typical example of dimerization reaction is the photoreaction of diacetyl (Scheme 5) which contributes the butter flavor. A cyclic dimer 1,4-dihydroxyl-l,4-dimethylcyclohexane-2,5-dione is obtained from photoreaction of diacetyl in hexane or ether (Bowen and Horton, 1934). However, when this photoreaction is conducted in an alcoholic solution, dimerization reaction of diacetyl is replaced by reduction reaction (Yamada and Hanai, 1951). This indicates that the photoreaction products of diacetyl in a solution depend on the solvent systems. 

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