Hydrogenation unfunctionalized

Tetrasubstituted alkenes are challenging substrates for enantioselective hydrogenation because of their inherently low reactivity. Crabtree showed that it was possible to hydrogenate unfunctionalized tetrasubstituted alkenes with iridium catalysts [46]. Among the iridium catalysts described in the previous section, several were found to be sufficiently reactive to achieve full conversion with al-kene 77 (Table 30.14). However, the enantioselectivities were significantly lower than with trisubstituted olefins, and higher catalyst loadings were necessary. 

As shown in Scheme 1.30, the chiral titanocene catalyst 34 hydrogenates unfunctionalized, disubstituted styrenes under 136 atm of hydrogen at 65°C to give the saturation products with 83 to >99% ee [156]. A high enantioselectivity is now realized only with aryl-substituted olefins. The enantioselectivity of 41% ee attained 2-ethyl-1-hexene and 34 as catalyst is the highest for hydrogenation of non-aromatic olefins. 

In the area of the asymmetric hydrogenation of C=C double bonds, the reduction of unfunctionalized olefins has been scarcely explored, in comparison with... 

In acyclic systems, the enolate conformation comes into play. p,(3-Disubstituted enolates prefer a conformation with the hydrogen eclipsed with the enolate double bond. In unfunctionalized enolates, alkylation usually takes place anti to the larger substituent, but with very modest stereoselectivity. 

The hydrogenation of unfunctionalized alkenes is readily performed by Group III and lanthanide cyclopentadienyl hydride derivatives, one key feature being the high TOFs of these systems (up to 120000 IT1 for hydrogenations catalyzed by Lu, Tables 6.8 and 6.9) [119, 120]. The reaction rate depends heavily on the metal and the ligands. It is inversely proportional to the metal radius (Lu>Sm>Nd>La), and it is faster for the Cp M derivatives than for the ansa di-... 

P,N and non-phosphorus ligands have been most successful in the enantiomeric iridium-catalyzed hydrogenation of unfunctionalized alkenes [5], and for this reason this chapter necessarily overlaps with Chapter 30. Here, the emphasis is on ligand synthesis and structure, whereas Chapter 30 expands on substrates, reaction conditions and reaction optimization. However, a number of specific substrates are mentioned in the comparison of catalysts, and their structures are illustrated in Figure 29.1. 

The highest enantioselectivity in the hydrogenation of unfunctionalized tri-substituted alkenes has been achieved with catalyst 14 a. The same catalyst was also used to hydrogenate a,/ -unsaturated phosphonates with enantiomeric excesses (ee) of 70 to 94% [8]. 

Finally, the phosphinite-oxazole catalyst 29 (Fig. 29.16) was recently reported and used to hydrogenate a series of functionalized and unfunctionalized alkenes [31]. It was anticipated that the planar oxazole unit and the fused ring system would improve the enantioselectivity compared to the PHOX catalyst by increasing rigidity in the six-membered chelating ring [32]. Indeed, these catalysts... 

Knochel and coworkers synthesized a series of camphor-derived pyridine and quinoline P,N ligands. The catalysts 30 (Fig. 29.17) were used to hydrogenate substrates 1 and 2 in up to 95% and 96% ee, respectively [33]. The selectivities were moderate for other unfunctionalized alkenes however, a high enantioselec-tivity was reported for the hydrogenation of ethyl acetamidocinnamate 10 [34]. 

Another series of achiral iridium catalysts containing phosphine and heterocyclic carbenes have also been tested in the hydrogenation of unfunctionalized alkenes [38]. These showed similar activity to the Crabtree catalyst, with one analogue giving improved conversion in the hydrogenation of 11. 

Catalyst 35b was used by Buchwald and coworkers with [PhMe2NH]+-[(BC6F5)4] to hydrogenate tetrasubstituted unfunctionalized cyclic olefins with... 

The most selective - and also most general - titanocene catalyst is complex 35 d, also studied by Buchwald and coworkers. This catalyst was used to hydrogenate a variety of functionalized and unfunctionalized cyclic and acyclic alkenes with excellent ee-values in most cases [46]. Enamines could also be hydrogenated with enantiomeric excesses of 80-90% [47]. However, high catalyst loadings (5-8 mol%) and long reaction times were required to drive the reactions to completion. 

Marks and coworkers developed a series of cyclopentadienyl-lanthanide complexes. In the initial investigations on achiral catalysts 36a and 36b (Fig. 29.21), TOFs greater than 100000 IT1 were observed in the hydrogenation of 1,2-disub-stituted unfunctionalized alkenes [48]. 

Aided by these developments, the past five years has seen a rapid growth in this area. A breakthrough was the introduction of iridium catalysts with chiral P,N ligands. A large number of new P,N and other ligands have been synthesized and applied to the hydrogenation of unfunctionalized alkenes. This chapter details the catalysts, conditions and substrates used in the enantiomeric hydrogenation of unfunctionalized alkenes. 

Substrate 2 has also been used as a test substrate HPLC separation methods exist for 2, while ee-value determination of 1 is more difficult [6, 17]. Reflecting the general recent interest in the hydrogenation of unfunctionalized olefins, the past few years have seen the publication of a number of results for this substrate [15, 18-26]. The highest enantioselectivities were achieved using catalysts 12b [22] and 14a [26],... 

As discussed below, Ir complexes derived from chiral P,N ligands have become the catalysts of choice for the enantiomeric hydrogenation of unfunctionalized trisubstituted olefins. Therefore, the most important characteristics of these catalysts are briefly summarized here [30-32]. 

Recently, a breakthrough in the hydrogenation of unfunctionalized olefins was made [51]. For the first time, high enantioselectivities with purely alkyl-substituted alkenes such as 72-74 could be achieved using pyridine-phosphinite catalysts 75 and 76. 

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