Air-stable racemization catalysts

DKR of Secondary Alcohols with Air-Stable Racemization Catalysts... 

The method is not restricted to secondary aryl alcohols and very good results were also obtained for secondary diols [39], a- and S-hydroxyalkylphosphonates [40], 2-hydroxyalkyl sulfones [41], allylic alcohols [42], S-halo alcohols [43], aromatic chlorohydrins [44], functionalized y-hydroxy amides [45], 1,2-diarylethanols [46], and primary amines [47]. Recently, the synthetic potential of this method was expanded by application of an air-stable and recyclable racemization catalyst that is applicable to alcohol DKR at room temperature [48]. The catalyst type is not limited to organometallic ruthenium compounds. Recent report indicates that the in situ racemization of amines with thiyl radicals can also be combined with enzymatic acylation of amines [49]. It is clear that, in the future, other types of catalytic racemization processes will be used together with enzymatic processes. 

All the Ru-based racemization catalysts described earUer are air-sensitive and thus difficult to reuse. We found that a modified Ru complex 7 was air-stable and recyclable, in particular, in a polymer-supported form 8. The racemization of secondary alcohols with 7 took place equally well under both oxygen and argon atmospheres. The subsequent DKRs of several alcohols using 7 or 8 under aerobic... 

We synthesized 8 by the one-step reaction of [Ph4(Tl -C4CO)]Ru(CO)3 with benzyl chloride. In contrast to previous alcohol racemization catalysts, 8 was stable in the air during racemization [30]. The racemization was performed even under 1 atm of molecular oxygen. Thus, alcohol DKR was for the first time possible with 8 in the air at room temperature (R)-l-phenylethyl acetate (99% yield, greater than 99%e.e.) was obtained from 1-phenylethanol by using 4mol% of 8, CALB and isopropenyl acetate in the presence of potassium phosphate (Scheme 1.22). This catalyst system was effective for both benzylic and aliphatic alcohols. The synthetic method for 8 was applied to the preparation of a polymer-bound derivative (9). Hydroxymethyl polystyrene was reacted with 4-(chloromethyl)benzoyl chloride to... 

As an excellent complement to the Pd-catalyzed methodology that has been utilized in a number of applications, in general experimentally simple and inexpensive catalyst system for the N-arylation of a wide variety of azoles (pyrrole, indoles, 7-azaindole, carbazole) has been developed (Equation 37) <2001JA7727>. In particular, it was shown that the combination of air stable Cul and racemic ( )-l,2-cyclohexanediamine 186a in the presence of K3PO4 is an extremely efficient and general catalyst system for the N-arylation of a number of azoles. Competitive C-arylation under these conditions is not observed. 

In contrast to CAMP, DIPAMP is a stable solid that melts at 102 °C. Heated at 100 °C, it has a half-life of 3-5 h. This racemization was somewhat faster than Mislow s phosphanes, which did not invert appreciably until 10-15 °C higher. The rate was reasonable, if one considers that inversion at either end destroys chirality. DIPAMP complexed to rhodium must invert much more slowly because efficient, asymmetric hydrogenations have been obtained at 95-100°C. For the sake of convenience, particularly on a large scale, a solid complex was made by reacting two equivalents of phosphane with one equivalent of [Rh(cod)Cl]2 in alcohol. This air-stable orange solid [Rh(bisligand)(cod)]+BF4 made a most suitable catalyst precursor. 

The catalyst precursor, 1, is air-stable which simplifies handling operations on a manufacturing scale. Despite these advantages, ligand synthesis is very difficult. After the initial preparation of menthylmethylphenylphosphinate (6), the (R)P-isorrier is separated by two fractional crystallizations (Fig. 6). The yield of (R,R)-DI-PAMP (8) is 18% based on 7 [9]. Another disadvantage is that the (R.R)-DIPAMP can racemize at 57 °C, which can be problematic since the last step is performed at 70 °C. Once the ligand is coordinated to rhodium, however, racemization is no longer a problem. 

Similarly, a [Pd2(dba)3]/dppb catalyst in toluene at 100 °C isomerizes PhC(O)—C=C—Bu into the dienone PhC(0)CH=CH—CH=CHEt in good yields. A variety of dienones has been prepared in this way. " There can be little doubt that all these reactions proceed via Pd Tr-allyl intermediates. The asymmetric isomerization of 4-hydroxycyclopent-2-en-l-one is catalyzed by [(R)-BINAP)Rh(MeOH)2] and gives 4-hydroxycyclopent-3-en-l-one as the primary product. With racemic starting material, the 5 enantiomer is consumed faster, to give a 5 1 enantiomeric discrimination. The primary product can tautomerize to 1,3-cyclopentadione. The same chiral cationic rhodium catalyst is also effective in the asymmetric isomerization of allylamines. Water impurities deactivate the catalyst. One such deactivation product is the air-stable trinuclear cluster (20), which was characterized by X-ray diffreaction. "" ... 

Buchwald and co-workers reported that the combination of air stable Cul (instead of the air sensitive CuOTf) and racemic trans-1,2-cyclohexanediamine (ligand la), in the presence of K3PO4, K2CO3, CS2CO3, or f-BuONa comprises an extremely efficient and general catalyst for the iV-amidation of aryl and heteroaryl halides (eq 9) and the Ai-arylation of a number of heterocycles (eq 10). This approach tolerates functional groups such as primary or secondary amides, free OH or NH on the aryl halides, which were problematic with the Pd-catalyzed amination methodology. 

---