Enol acetates, asymmetric hydrogenation

After succeeding in the asymmetric reductive acylation of ketones, we ventured to see if enol acetates can be used as acyl donors and precursors of ketones at the same time through deacylation and keto-enol tautomerization (Scheme 8). The overall reaction thus corresponds to the asymmetric reduction of enol acetate. For example, 1-phenylvinyl acetate was transformed to (f )-l-phenylethyl acetate by CALB and diruthenium complex 1 in the presence of 2,6-dimethyl-4-heptanol with 89% yield and 98% ee. Molecular hydrogen (1 atm) was almost equally effective for the transformation. A broad range of enol acetates were prepared from ketones and were successfully transformed into their corresponding (7 )-acetates under 1 atm H2 (Table 19). From unsymmetrical aliphatic ketones, enol acetates were obtained as the mixtures of regio- and geometrical isomers. Notably, however, the efficiency of the process was little affected by the isomeric composition of the enol acetates. 

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

Ci-TunePhos-modified Pd catalysts have found applications in allylic asymmetric alkylations, asymmetric hydrogenations of a- and /3-ketoesters <2006SL1169, 2000JOC6223>, allylphthalimides <2005AGE4933>, enol acetates <2002OL4495>, and asymmetric cycloadditions <2005TL8213>. 

Monodentate phosphoramidites, in particular (9) and its octahydro analogue, are found to be excellent ligands for the rhodium-catalysed asymmetric hydrogenation of aromatic enol acetates, enol carbamates, and 2-dienol carbamates with up to 98%... 

Rh(COD)(/ ,/ -DIPAMP)]+BF4- (13) has shown remarkable activity and enantioselectivity in the asymmetric hydrogenation of various enamides, enol acetates, and unsaturated olefins.20 26 For the past 20 years, 13 has been the premier asymmetric homogeneous catalyst for amino acid synthesis, but a new generation of catalysts based on novel bisphosphines (vide infra) has surpassed it in versatility. 

A chiral ligand system based on C2-symmetric chiral bis(phospholanes) (5 and 6) has shown to be a powerful ligand in the asymmetric hydrogenation of various substrates that include enamides, enol acetates, C=N bond reduction, and P-keto esters. Detailed discussions of this class of ligands are included Chapter 18. 

In order for these rhodium DuPHOS catalysts to achieve the desired reactivity and selectivity, the hydrogenation substrate must contain certain features to facilitate the highly diastereoselective transition state required for the reaction. All the substrates to which rhodium DuPHOS hydrogenation catalysts have been successfully applied thus far possess a donor atom y to the olefin (Fig. 2). Within the constraint of this geometric requirement a wide array of prochiral olefins have been demonstrated as suitable substrates for asymmetric hydrogenation with rhodium DuPHOS catalysts. Examples include enamides 2 [1, 2], vinylacetic acid derivatives 3 [3], and enol acetates 4 [4]. 

Asymmetric hydrogenation. A precursor of (5,5)-CHIRAPHOS has been obtained from asymmetric hydrogenation of 2,3-bis(diphenylphosphinoyl)-1,3-butadiene. Chiral l,l,l-trifluoroalkan-2-ols can be synthesized from enol acetates of the trifluoromethyl ketones. A general method for accessing secondary alcohols from aromatic and heteroaromatic ketones is by asymmetric hydrogenation with the complex 1. 

In the search for new ligands for asymmetric catalysis Ben L. Feringa and coworkers developed the synthesis of chiral monodentate phosphoramidites (PipPhos) (Figure 3.20) which were excellent ligands for asymmetric hydrogenation of aromatic enol acetates, and enol carbamates with high ee values up to 98%. 

Tang W, Liu D, Zhang X (2003) Asymmetric hydrogenation of itaconic acid and enol acetate derivatives with the Rh-TangPhos catalyst. Org Lett 5 205-207... 

The asymmetric hydrogenation of cyclic enol acetate has also proven to be a challenging problem. In this respect, Me-PennPhos 125 was shown to be an effective ligand in the rhodium-catalyzed asymmetric hydrogenation of five- or six-membered cyclic enol acetates such as 172. " In addition, Tang et al. found that the TangPhos-Rh catalyst system provided good-to-excellent (92%-99%) enantioselectivities for a diverse set of aryl enol acetates. ... 

We applied the DKR procedme to the asymmetric reductive acylation of ketones and the asymmetric hydrogenation of enol acetates [16]. In the asymmetric reductive... 

Five sequential reactions in the asymmetric hydrogenation of enol acetates. 

In the asymmetric reduction of enol acetates, five different reactions take place sequentially deacetylation of enol acetate, keto-enol isomerization, hydrogenation of ketone, and finally racemization and resolution of alcohol for DKR (Scheme 5.10). Here, the enol acetate acts as both the precursor of ketone and the acyl donor. The overall transformation was performed with Novozym 435 and Shvo s catalyst in the presence of hydrogen molecule or 2,6-dimethylheptan-4-ol as the hydrogen donor to provide the products of high enantiopurity with good )delds in most cases (Scheme 5.11 and Chart 5.8). 

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