Hydroformylation of unsaturated alcohols

Alkenyl and Alkynyl alcohols. RhodiuiO Catalyzed hydroformylation of unsaturated alcohols provides useful intermediates for organic syntheses. 

The rhodium-catalyzed hydroformylation of unsaturated alcohols is useful for the synthesis of important intermediates in organic synthesisThe hydroformylation of homoallylic alcohols has been shown to give isolable lactols, which can be further oxidized to the corresponding lactonesJ ... 

This hydroformylation of unsaturated alcohols having strongly steri-cally shielded double bonds has been described by D. C. Hull ef aL [281]. As expected, the formyl group is attached to carbon atom 5 (see the details over olefins on page 38). 

Most ring syntheses of this type are of modern origin. The cobalt or rhodium carbonyl catalyzed hydrocarboxylation of unsaturated alcohols, amines or amides provides access to tetrahydrofuranones, pyrrolidones or succinimides, although appreciable amounts of the corresponding six-membered heterocycle may also be formed (Scheme 55a) (73JOM(47)28l). Hydrocarboxylation of 4-pentyn-2-ol with nickel carbonyl yields 3-methylenetetrahy-drofuranone (Scheme 55b). Carbonylation of Schiff bases yields 2-arylphthalimidines (Scheme 55c). The hydroformylation of o-nitrostyrene, subsequent reduction of the nitro group and cyclization leads to the formation of skatole (Scheme 55d) (81CC82). 

The hydroformylation of unsaturated nitriles such as crotonitrile and allyl cyanide is a potential route towards chiral amino alcohols, which are building blocks in the synthesis of pharmaceuticals. The hydroformylation of acrylonitrile was studied in the early years [5], but lately the hydroformylation of allyl cyanide and crotonitrile have also been investigated [25,81]. 

Hydroformylation of unsaturated amines offer a convenient synthetic access to cyclic AT.O-hemiacetals. If performed in the presence of alcohols or orthoesters AT,O-acetals are formed. With additional N-nucleophiles N,N-acetals are obtained. These compounds are synthetically attractive building blocks and were therefore used as a key step in the synthesis of various natural products [27,35]. Thus the synthesis of (+)-prosopinine starting from enantiopure (T)-scrinc leads to a cyclic N,O-acetal functionality with the required functionality for the attachment of the side chain (Scheme 6) [36]. 

Cyclization also accompanies the hydroformylation of unsaturated C4-alcohols catalyzed by a rhodium/PNS (27) complex (Scheme 4.14). Interestingly, an approximately 3-fold increase was observed in the activity of the catalyst upon increasing the pH from 7 to 9.5 [95]. Rhodium could be efficiently recycled in the aqueous phase, but since there was a considerable pH-drop during the reaction (from 9 to 5) the activity of the catalyst had to be regenerated by addition of a base (NaOH). 

Table II. Hydroformylation of Dienes and Polyenes Table III. Hydroformylalion of Unsaturaled Alcohols. ...

TABLE V. HYDROFORMYLATION OF UNSATURATED ESTERS A. Esters of Unsaturated Alcohols... 

Besides acids and esters, the corresponding unsaturated long-chain alcohols have also been subjected to the addition of syngas [52]. For example, the hydroformylation of oleic alcohol, in which the substrates can be prepared by heterogeneous hydrogenation of oleic acid esters [53] using a sulfonated triphenylphosphine as a ligand under neat conditions, has been described in a patent of Ruhrchemie (Scheme 6.96) [54]. 

Hydroformylation Reactions of Unsaturated Alcohol and Ester Inspired by the excellent performance of the supported IL-phase catalyst in the hydroformylation reactions of olefins, its catalytic activity in the hydroformylation reaction of unsaturated alcohol and ester was also explored. Scheme 2.22 [95]. The supported IL catalysts were prepared via impregnation of silica gel in a dichloromethane solution of HRhCOfPPhjjj, PPhj, and IL[BMIm][PFJ(Rh/PPh3/SILPC).Allyl alcohols with different structures could be smoothly transformed into the corresponding aldehydes with about 90% yields. The ratio of linear aldehyde to branched aldehyde was about 22. In succession, Rh/PPhj/SILPC was removed and Ru/PPhj/SILPC was added directly, and the aldehyde could be completely converted to diol after the hydrogenation reaction. 

The synthesis of tetrahydrofuran derivatives from unsaturated alcohols via hydroformylation intermediates was developed many years ago. Moderate yields are obtained from but-2-en-l,4-diol (Scheme 54)94 but hydroformylation is not the major pathway when coniferyl alcohol is subjected to the oxo process (Scheme 55).9S A more complicated reaction is involved... 

Rosenthal and co-workers (91, 92) studied the cobalt hydroformylation of various unsaturated carbohydrates. As with other a,j8-unsaturated ethers, addition of the formyl group occurred almost exclusively at the double-bond carbon a to the oxygen. High yields of product were obtained, but hydrogenation to alcohol was facile, even under mild conditions, as noted in Eq. (43) ... 

The interaction of unsaturated molecules, for example olefins and acetylenes, with transition metals is of paramount importance for a variety of chemical processes. Included among such processes are stereospecific polymerization of olefin monomers, the production of alcohols and aldehydes in the hydroformylation reaction, hydrogenation reactions, cyclo-propanation, isomerizations, hydrocyanation, and many other reactions. 

The synthesis of aldehydes or ketones by dehydrogenation of alcohols is one chemical route of many possible alternatives. The hydroformylation of olefins is the most utilized synthetic route, although dehydrogenation has found a place in the production of fragiunce aldehydes. From the Ullmann Encyclopedia [40] it is apparent that dehydrogenation becomes predominant when the carbon number is Cg or more for straight-chain aldehydes. The unsaturated Cio aldehydes from the transformation of essential oils are a second important field where dehydrogenation is often employed (Table 1). 

The catalytic processes, which operate via mechanisms that cycle between Rh(I) and Rh(III) intermediates, include (1) hydrogenation (the activation of H2 for the reduction of unsaturated organic compounds), (2) hydroformylation (the activation of H2 and CO for their addition to olefins to generate aldehydes or alcohols) and (3) carbonylation (the activation of CO for its addition to organics). Some of the processes have been developed commercially. 

Nevertheless, it must be pointed out that the formation of such transient species has never been spectroscopically observed. Native CDs are effective inverse phase-transfer catalysts for the deoxygenation of allylic alcohols, epoxydation,or oxidation " of olefins, reduction of a,/ -unsaturated acids,a-keto ester,conjugated dienes,or aryl alkyl ketones.Interestingly, chemically modified CDs like the partially 0-methylated CDs show a better catalytic activity than native CDs in numerous reactions such as the Wacker oxidation,hydrogenation of aldehydes,Suzuki cross-coupling reaction, hydroformylation, " or hydrocarboxylation of olefins. Methylated /3-CDs were also used successfully to perform substrate-selective reactions in a two-phase system. 

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