Rhodium catalyzed hydroformylation-acetalization

Preferentially, acetals were obtained by the Kalck group in the rhodium-catalyzed hydroformylation- acetalization reaction of (l/J,4/ )-isolimonene in the presence of triethyl orthoformate (Scheme 5.76) [64]. The reaction with P-pinene gave a mixture of diastereomeric acetals. Increasing temperatures forced the... 

Another route to the diol monomer is provided by hydroformylation of allyl alcohol or allyl acetate. Allyl acetate can be produced easily by the palladium-catalyzed oxidation of propylene in the presence of acetic acid in a process similar to commercial vinyl acetate production. Both cobalt-and rhodium-catalyzed hydroformylations have received much attention in recent patent literature (83-86). Hydroformylation with cobalt carbonyl at 140°C and 180-200 atm H2/CO (83) gave a mixture of three aldehydes in 85-99% total yield. 

The asymmetric hydroformylation of functionalized aliphatic alkenes is generally more difficult than the hydroformylation of vinyl arenes. The rhodium-catalyzed hydroformylation of vinyl acetate (36) yields 2- and 3-acetoxypropanals, 37 and 38, with high chemoselectivity. Ethyl acetate and acetic acid can also be found as by-products. One of the potential applications of vinyl acetate hydroformylation is the production of enantiopure propane 1,2-diol (Scheme 6). 

Rhodium-catalyzed hydroformylation of 2-amino-/V-(but-3 -enyl)- and -A-(3 -rnethylbut-3 -enyi)benzylamines (381) in the presence of rho-dium(II) acetate dimer and triphenylphosphine in deoxygenated ethyl acetate gave mixtures of 5,5a,6,7,8,9-hexahydro-llH-pyrido[2,l-b]quinazo-line (382), isomeric 6-methyl-5,5a,6,7,8,10-hexahydropyrrolo[2,l-b]quina-zolines (383), and 6-methyl-6,7,8,10-tetrahydropyrrolo[2,l-ft]quinazoline (384), as well as a stereoisomeric mixture of 7-methyl-5,5a,6,7,8,9-hexahy-dro-ll//-pyrido[2,l-b]quinazolines (385) and 15% of 7-methyl-6,7,8,9-tetrahydro-llH-pyrido[2,l-fr)quinazolme (386), (95AJC2023). When the bulky tricyclohexylphosphine was used instead of triphenylphosphine, a 3 7 mixture of compounds 382 and 383 and a 3 1 mixture of isomeric 385 were formed. 

Rhodium-catalyzed hydroformylation of -(substituted amino)benzyl-amines (387, X = H2) and -(substituted amino)benzamides (387, R = H, X = O) in the presence of rhodium(II) acetate dimer and triphenylphos-phine in deoxygenated ethyl acetate gave a 7 3 mixture of 1,2,3,4,4 ,5-hexahydro-6//-pyrido[l,2-a]quinazolines (388, X = H2,0) and isomeric 3-methyl-l,2,3,3fl,4,5-hexahydropyrrolo[l,2-a]quinazolines (389, X = H2, O) (94AJC1061). The methyl derivative of benzylamine 387 (R = Me, X = H2) afforded a mixture of diastereoisomers 390 and 391 (X = H2). Their ratio depended on the reaction time. Longer reaction times gave more 391 (X = H2), containing the methyl group in an equatorial position. Compound 390 isomerized into 391 (X = H2), under the aforementioned conditions. The benzamide derivative (387, R = Me, X = O) yielded only one isomer (391, X = O), independent of the reaction period. 

Starting from butenediol acetate (28), a further carbon atom is introduced by rhodium-catalyzed hydroformylation, likewise after a copper-catalyzed allyl rearrangement to give vinylglycol diacetate. Splitting of an acetyl group leads to the P-formylcrotyl acetate (8 b) (C5 acetate) 34 a). 

The C5 aldehyde intermediate is produced from butadiene via catalytic oxidative acetoxylation followed by rhodium-catalyzed hydroformylation (see Fig. 2.30). Two variations on this theme have been described. In the Hoffmann-La-Roche process a mixture of butadiene, acetic acid and air is passed over a palladium/tellurium catalyst. The product is a mixture of cis- and frans-l,4-diacetoxy-2-butene. The latter is then subjected to hydroformylation with a conventional catalyst, RhH(CO)(Ph3P)3, that has been pretreated with sodium borohydride. When the aldehyde product is heated with a catalytic amount of p-toluenesulphonic acid, acetic acid is eliminated to form an unsaturated aldehyde. Treatment with a palladium-on-charcoal catalyst causes the double bond to isomerize, forming the desired Cs-aldehyde intermediate. 

Finally, water-soluble phosphorylated BlNAPs were tested as ligands in aqueous biphasic rhodium-catalyzed hydroformylation of vinyl acetate. Compared with catalysts prepared with the parent ligand in a homogeneous medium, the chemo-, regio- and enantioselectivities were markedly lower [24]. 

S,S)-Chiraphite was also screened in the rhodium-catalyzed hydroformylation of allyl cyanide bll = 5.8 1, 14% ee) and vinyl acetate bll = 246 1, 49% ee), but it was found to be clearly inferior to (5,5,5)-Bisdiazaphos (see below) [16]. Moreover, the hgand induced worse results in the hydroformylation of allyl cyanide in comparison to (R,S)-BINAPHOS and (S,5)-Kelliphite [37]. It was also less efficient... 

Hydroformylation of Aliphatic Olefins In 1997, Herrmann and coworkers [25] were the first to use NHCs and imidazohum salts, respectively, as hgands or preligands in rhodium-catalyzed hydroformylation. The isolated NHC-rhodium complexes 1 and 2 (Figure 2.55) and the complexes prepared in situ from the water-soluble imidazolium salts 3a-c and rhodium(lll)acetate were tested in the homogeneous and biphasic hydroformylation of propene. The catalyst derived from 1 produced >99% yield of isomeric butanals (CO/H2 = 1 1,10 MPa S/C = 100 000 1, toluene, 60 h). In the biphasic system, after 20 h of reaction time and S/C = 10000 1 in water, rhodium catalysts derived from 2 or based on hgands 3a-c allowed up... 

Figure 5.15 P-ligands suitable for rhodium(l)-catalyzed hydroformylation-acetalization of...

Bestmann s ylide 0=C=C=PPh3 as a Cj buUding block (Scheme S.ldO). ) The required substrate was derived by the rhodium-catalyzed addition of acetic acid to a terminal alkyne. For the asymmetric rhodium-catalyzed hydroformylation at 10.3 bar, Landis s (S,S,S)-BDP was used as ligand. After hydroformylation and ring closure, the protecting 0-acetyl group was removed by the effect of an enzyme to finally produce (+)-patulolide C in an overall yield of 49%. 

Rhodium-catalyzed hydroformylation of linalool gave almost quantitatively a cyclic hemiacetal in toluene solutions (Route I) and a corresponding mixed acetal in ethanol solutions (Route II, Scheme 6.48) [93, 145]. The reaction occurred 2 times faster in ethanol than in toluene solutions and 10 times faster with the Rh/P(O-0-iBuPh)3 system as compared to the catalytic system with PPhj as ligand. Recently, the reaction was run successfully in an aqueous two-phase system [94]. Both hemiacetal and acetal are compounds with fresh floral and/or citrus notes [22a]. 

The most common oxidatiou states and corresponding electronic configurations of rhodium are +1 which is usually square planar although some five coordinate complexes are known, and +3 (t7 ) which is usually octahedral. Dimeric rhodium carboxylates are +2 (t/) complexes. Compounds iu oxidatiou states —1 to +6 (t5 ) exist. Significant iudustrial appHcatious iuclude rhodium-catalyzed carbouylatiou of methanol to acetic acid and acetic anhydride, and hydroformylation of propene to -butyraldehyde. Enantioselective catalytic reduction has also been demonstrated. 

Rhodium-Catalyzed Asymmetric Hydroformylation of Vinyl Acetate. .. 52... 

Rhodium( I)-catalyzed hydroformylation of cyclic enol acetals 1 leads to acetal-protected syn-3,5-dihydroxyalkanals 2 with extraordinarily high levels (>50 1) of diastereoselectivity (Scheme 5.2) [2]. The diastereoselectivity cannot be ascribed to any obvious steric bias, and serves as a powerful demonstration that the hydroformylation reaction may be subject to exquisite stereoelectronic control. Indeed, while the addition of a pseudo-axial methyl group to the acetal carbon (as in acetonide 3) has a deleterious effect on the rate of the reaction, the sy -diastereomer 4 is still produced selectively, in what is surely a contra-steric hydroformylation reaction. 

Recently, and for the first time, it has been shown that high levels of diastereocontrol may be realized in the rhodium(l)-catalyzed hydroformylation of acychc alkenes. In one example, acetals 10 afford aldehydes 11 with superior diastereoselectivity (Scheme 5.4) [4]. This result was attributed to a strong conformational bias in the substrate, as shown. Evidence for this conformational bias was secured by 2D-NOESY NMR experiments and MM3 force field calculations. When the experiment was repeated with R=H, the diastereoselectivity was lost, lending further support to the model. 

The approach to polyketide synthesis described in Scheme 5.2 requires the relatively nontrivial synthesis of acid-sensitive enol acetals 1. An alternative can be envisioned wherein hemiacetals derived from homoallylic alcohols and aldehydes undergo dia-stereoselective oxymercuration. Transmetallation to rhodium could then intercept the hydroformylation pathway and lead to formylation to produce aldehydes 2. This proposal has been reduced to practice as shown in Scheme 5.6. For example, Yb(OTf)3-cata-lyzed oxymercuration of the illustrated homoallyhc alcohol provided organomercurial 14 [6]. Rhodium(l)-catalyzed hydroformylation of 14 proved successful, giving aldehyde 15, but was highly dependent on the use of exactly 0.5 equiv of DABCO as an additive [7]. Several other amines and diamines were examined with variation of the stoichiometry and none proved nearly as effective in promoting the reaction. This remarkable effect has been ascribed to the facilitation of transmetallation by formation of a 2 1 R-HgCl DABCO complex and the unique properties of DABCO when both amines are complexed/protonated. 

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