Heck-hydroformylation

To also add an application to aromatic compounds we cite the Heck-hydroformylation sequence [57] (see 121) and to extend these directed additions into the silicon and boron field a regioselective silylformylation-allyl silylation sequence [58] and a hydroformylation-allyl boration hydroformylation cascade are included. 

Many organic chemical transformations have been carried out in ionic liquids hydrogenation [4, 5], oxidation [6], epoxidation [7], and hydroformylation [8] reactions, for example. In addition to these processes, numerous synthetic routes involve a carbon-carbon (C-C) bond-forming step. As a result, many C-C bondforming procedures have been studied in ambient-temperature ionic liquids. Among those reported are the Friedel-Crafts acylation [9] and allcylation [10] reactions, allylation reactions [11, 12], the Diels-Alder reaction [13], the Heck reaction [14], and the Suzuld [15] and Trost-Tsuji coupling [16] reactions. 

Much of the recent interest in insertion reactions undeniably stems from the emphasis placed on development of homogeneous catalysis as a rational discipline. One or more insertion is involved in such catalytic processes as the hydroformylation (31) or the polymerization of olefins 26, 75) and isocyanides 244). In addition, many insertion reactions have been successfully employed in organic and organometallic synthesis. The research in this general area has helped systematize a large body of previously unrelated facts and opened new areas of chemistry for investigation. Heck 114) and Lappert and Prokai 161) provide a comprehensive compilation and a systematic discussion of a wide variety of insertion reactions in two relatively recent (1965 and 1967) reviews. 

A typical example of this is the dicobalt octacarbonyl catalyzed hydroformylation of olefins to yield aldehydes. According to the classical mechanism proposed by Heck and Breslow /29/ (Equations 28-31), the cobalt carbonyl reacts with hydrogen to form hydrido cobalt tetracarbonyl, which is in equilibrium with the coordinatively unsaturated HCo(C0)2. The tricarbonyl coordinates the olefin, and rearranges to form the alkyl cobalt carbonyl. 

Thus, [HRh(C0)(TPPTS)3]/H20/silica (TPPTS = sodium salt of tri(m-sulfophenyl)phopshine) catalyzes the hydroformylation of heavy and functionalized olefins,118-122 the selective hydrogenation of a,/3-unsaturated aldehydes,84 and the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic add (a precursor of naproxen).123,124 More recently, this methodology was tested for the palladium-catalyzed Trost Tsuji (allylic substitution) and Heck (olefin arylation) reactions.125-127... 

For the phosphine-substituted cobalt carbonyl hydroformylations, it is probable that the mechanism follows the pathway of Heck and Breslow (77, 18), although the possibility of an associative mechanism has been raised (7). The increased stability of the HCo(CO)3PR3 complexes toward loss of CO was cited as being suggestive of a nondissociative pathway. 

In the presence of tetramethyltin, 1-bromonauclefine reacts with CO in a Pd-catalyzed carbonylation to give the alkaloid naucletine [202], Dong and Busacca effected a new synthesis of tryptamines and tryptophols via a Rh-catalyzed hydroformylation of functionalized anilines that are prepared by a standard Heck reaction, as shown for the preparation of tryptamine sulfonamide 325 [423]. This reaction is applicable to ring-substituted tryptamines (Cl, Br, F. OMe, CF3). Likewise, the Rh-catalyzed carbonylation of o-alkynylanilines, which were prepared by a Pd-catalyzed Sonogashira coupling, leads to oxindoles (60-86% yields) [424],... 

The intermolecular Heck reaction of 3-bromofuran and tosylallyamine 88 gave adduct 89 under the classical Heck conditions [79], Subsequent Rh-catalyzed hydroformylation with ring closure occurred regioselectively to furnish the hydroxypyrrolidine, which was dehydrated using catalytic HC1 to afford dihydropyrrole 90. 

Figure 2 shows the generally accepted dissociative mechanism for rhodium hydroformylation as proposed by Wilkinson [2], a modification of Heck and Breslow s reaction mechanism for the cobalt-catalyzed reaction [3]. With this mechanism, the selectivity for the linear or branched product is determined in the alkene-insertion step, provided that this is irreversible. Therefore, the alkene complex can lead either to linear or to branched Rh-alkyl complexes, which, in the subsequent catalytic steps, generate linear and branched aldehydes, respectively. 

The first catalyst used in hydroformylation was cobalt. Under hydroformylation conditions at high pressure of carbon monoxide and hydrogen, a hydrido-cobalt-tetracarbonyl complex (HCo(CO)4) is formed from precursors like cobalt acetate (Fig. 4). This complex is commonly accepted as the catalytic active species in the cobalt-catalyzed hydroformylation entering the reaction cycle according to Heck and Breslow (1960) (Fig. 5) [20-23]. 

Although Eq. (3) indicates that CO absorption is required for aldehyde formation, it has been shown by Karapinka and Orchin 18) that at 25° and with a moderate excess of olefin the rate of reaction and the yield of aldehyde are similar when either 1 atm of CO or 1 atm of Nj is present. Obviously CO is not essential for the reaction and a CO-deficient intermediate, probably an acylcobalt tricarbonyl, can be formed under these conditions. The relative rates of HCo(CO)4 cleavage of tricarbonyl and tetracarbonyl are not known, and thus the stage at which CO is absorbed in the stoichiometric hydroformylation of olefins under CO is not known with certainty. Heck (19) has shown conclusively that acylcobalt tetracarbonyls are in equilibrium with the acylcobalt tricarbonyl ... 

The use of catalytic SILP materials has been reviewed recently [10] covering Friedel-Crafts reactions [33-37], hydroformylations (Rh-catalyzed) [38], hydrogenation (Rh-catalyzed) [39,40], Heck reactions (Pd-catalyzed) [41], and hydroaminations (Rh-, Pd-, and Zn-catalyzed) [42]. Since then, the SILP concept has been extended to additional catalytic reactions and alternative support materials. In this paper we will present results from continuous, fixed-bed carbonylation and hydroformylation reactions using rhodium-based SILP catalysts as reaction examples demonstrating the advantages of the SILP technology for bulk chemical production. 

Triphenylphosphine-Functionalized Amphiphiles for Rhodium-Catalyzed Hydroformylation and Palladium-Catalyzed Heck Coupling Reaction... 

In a first test reaction, the polymer support was used for the hydroformylation of 1-octene in water in the presence of Rh(CO)2acac. Within a reaction time of 10 h at 120°C and a H2/CO (1 1) pressure of 5 MPa, conversion of up to 94% was obtained. The n iso ratio was 3 1, sometimes reaching 9 1. The quantities of 3-and 4-nonanal resulting from olefin isomerization, were below 5% [74]. The versa-tihty of the polymer support was further demonstrated with the Heck reaction of styrene and iodobenzene in the presence of Pd(OAc)2 as the metal catalyst The reaction was again performed in pure water at 50 °C and product yield of up to 80% was obtained after 20 h reaction time [75]. 

The essential features of the alkene hydroformylation mechanism proposed by Heck and Breslow [61] remain intact, after many investigations using a variety of techniques. The cycle shown in Scheme 3.3 is that for the unmodified, cobalt... 

Initial studies showed that the encapsulated palladium catalyst based on the assembly outperformed its non-encapsulated analogue by far in the Heck coupling of iodobenzene with styrene [7]. This was attributed to the fact that the active species consist of a monophosphine-palladium complex. The product distribution was not changed by encapsulation of the catalyst. A similar rate enhancement was observed in the rhodium-catalyzed hydroformylation of 1-octene (Scheme 8.1). At room temperature, the catalyst was 10 times more active. For this reaction a completely different product distribution was observed. The encapsulated rhodium catalyst formed preferentially the branched aldehyde (L/B ratio 0.6), whereas usually the linear aldehyde is formed as the main product (L/B > 2 in control experiments). These effects are partly attributed to geometry around the metal complex monophosphine coordinated rhodium complexes are the active species, which was also confirmed by high-pressure IR and NMR techniques. 

Tppts is a white solid which is slightly air sensitive. Deaerated solutions of tppts are stable if stored under inert gas atmosphere. The 31P NMR (161.8 MHz, D20) exhibits a singlet at 8 — 5.1 ppm. Detailed NMR data can be found in reference 19. Tppts is widely used as a ligand for metal-catalyzed reactions in water (e.g., hydrogenation, hydroformylation, carbonylation, and Heck reactions).1... 

In 1961 Heck and Breslow presented a multistep reaction pathway to interpret basic observations in the cobalt-catalyzed hydroformylation.28 Later modifications and refinements aimed at including alternative routes and interpreting side reactions.6 Although not all the fine details of hydroformylation are equally well understood, the Heck-Breslow mechanism is still the generally accepted basic mechanism of hydroformylation.6,17,19,29 Whereas differences in mechanisms using different metal catalysts do exist,30 all basic steps are essentially the same in the phosphine-modified cobalt- and rhodium-catalyzed transformations as well. 

The present discussion is limited to the rhodium catalyzed hydroformylation. In the widely accepted mechanism proposed by Wilkinson et ah (36), on the basis of suggestions by Breslow and Heck (37) for the cobalt catalyzed hydroformylation, the reaction steps, with the exception of the hydrogenolysis of the acyl-rhodium complexes, correspond to equilibria (Scheme 10). 

Ionic liquids (continued) for Heck coupling, 1, 870 for homogeneous-multi-phase catalysis, 1, 856 for hydroformylations, 11, 450 for hydrogenations, 1, 857 for kinetic study monitoring, 1, 517 metalloorganic ILs, 1, 853 and molten salts, 1, 848... 

In this manner, a hydroformylation/condensation sequence of 0-vinyl-anilines give indoles directly. The starting o-vinylanilines are obtained by Heck reaction of the corresponding o-haloanilines. Hydroformylation of these styrene-type olefins proceeds preferably at the benzyl carbon. Intramolecular condensation gives pharmacologically interesting tryptophols and tryptamines in mediocre to good yields (Scheme 12, Table 1) [47]. 

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