Asymmetric hydroformylation and hydrocarboxylation of enamides. Synthesis of alanine and proline

Becker, Y.; Eisenstadt, A.; Stille, J. K.

doi:10.1021/jo01299a022

Cited by 99 publications

(31 citation statements)

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“…29 The less expensive chiral ligand (-)-DIOP was shown to be less efficient than the related ligand ( -)-DIPHOL as far as stereoselectivity is concerned: with the former ligand enantiomeric excesses up to 18% only were reached.27 N-Vinylphthalimide undergoes hydroformylation (50% conversion in 5 days) in the presence of Rh(I)/( -1-DIPHOL to yield the branched product almost exclusively, but in low ee (34.1%). Use of the [(-IDIPHOLlF't(SnC1,)Cl catalyst allowed a faster reaction with a higher ee (70%), but low aldehyde selectivity was obtained (57%) (Scheme 4).…”

Section: Cx-amino Acidsmentioning

confidence: 99%

The asymmetric hydroformylation in the synthesis of pharmaceuticals

Botteghi¹,

Paganelli²,

Schionato³

et al. 1991

Chirality

203

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The asymmetric hydroformylation reaction represents a potential powerful synthetic tool for the preparation of large number of different chiral products to be used as precursors of several organic compounds endowed with therapeutic activity. Essential and nonessential amino acids, 2-arylpropanoic acids, aryloxypropyl- and beta-phenylpropylamines, modified beta-phenylethylamines, pheniramines, and other classes of pharmaceuticals are available through enantioselective oxo-reaction of appropriate functionalized olefins; this process is catalyzed by rhodium or platinum complexes with chiral ligands, mainly chelating phosphines, and sometimes affords very high enantiomeric excesses. Furthermore, the application of many simple optically active aldehydes arising from asymmetric hydroformylation as chiral building blocks for the synthesis of complex pharmacologically active molecules such as antibiotics, peptides, antitumor macrocycle compounds, and prostaglandins is conveniently emphasized. The possibility of a future application of this asymmetric process for the production of many synthons to obtain other valuable pharmaceuticals is widely discussed too.

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Section: Cx-amino Acidsmentioning

confidence: 99%

The asymmetric hydroformylation in the synthesis of pharmaceuticals

Botteghi¹,

Paganelli²,

Schionato³

et al. 1991

Chirality

203

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“…[1][2][3][4][5][6] Applications that have been practiced at commercial scale include: polymer synthesis by co-polymerisation, methyl propionate synthesis by ethylene methoxycarbonylation and formation of racemic fine chemicals by hydroxycarbonylation of vinyl arenes (sometimes generated in situ from alcohols).…”

Section: Introductionmentioning

confidence: 99%

“…6 As part of a programme aiming to increase scope in this class of reaction, we have studied carbonylation of N-…”

Section: Introductionmentioning

confidence: 99%

“…5 There is also a relevant report of an attempted methoxycarbonylation of a 2-pyrroline derivative that gave none of the desired ester. 6 As part of a programme aiming to increase scope in this class of reaction, we have studied carbonylation of N-tosyl-3-pyrroline. Interest in the catalytic asymmetric synthesis of β-Proline derivatives is exemplified by a recent study reporting enantioselective hydroformylation of N-Boc-2-pyrroline, 7 while we recently reported the related transfer hydroformylation of N-tosyl pyrroline with around 70-75% e.e.…”

Section: Introductionmentioning

confidence: 99%

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Isomerisation versus carbonylative pathways in the hydroxy-carbonylation, methoxy-carbonylation, and amino-carbonylation of N-tosyl-3-pyrroline

Fuentes

Durrani

Leckie

et al. 2016

Catal. Sci. Technol.

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Abstract:The reactivity of N-tosyl-3-pyrroline is significantly lower than that of mono-substituted alkenes in Pd catalysed methoxycarbonylation reactions. For example, most bulky diphosphine/ Pd catalysts, including the well-known Pd catalyst derived from 1,2-bis(Di-TertButylPhosphinoXylene (DTBPX), were found to give no product at all in the methoxycarbonylation of N-tosyl-3-pyrroline. The competing pathways in methoxycarbonylation of N-methane-sulfonyl-3-pyrroline using Pd/ DTBPX were studied using DFT calculations; these show that the coordination of the alkene is unfavourable, and once coordinated, isomerisation is a lower energy pathway that ultimately leads to an alternative product. Experimentally a side product resulting from alkene isomerisation and addition of methanol is formed slowly (if CO is present), and rapidly if CO is not. A less bulky derivative of DTBPX forms the required alkene complex with much lower barriers. A study has been made of the enantioselective carbonylation of N-tosyl-3-pyrroline using water, methanol or aniline as nucleophile. This revealed that there is a range of possible products with most of these initiated by a Pd-catalysed isomerisation of the alkene. Using less bulky members of the Pd/Phanephos family of catalysts, it is possible to produce the methoxycarbonylation product from this poorly reactive alkene with reasonably good chemoselectivity and around 80% e.e. at higher pressures of CO. IntroductionPalladium catalysed alkene carbonylation is a very important reaction in industrial synthesis, since it uses very cheap reagents in a very atom efficient manner. [1][2][3][4][5][6] Applications that have been practiced at commercial scale include: polymer synthesis by co-polymerisation, methyl propionate synthesis by ethylene methoxycarbonylation and formation of racemic fine chemicals by hydroxycarbonylation of vinyl arenes (sometimes generated in situ from alcohols).1,2 A stand-out catalyst is the Pd complex formed from 1,2-bis(Di-Tert-ButylPhosphinoXylene (DTBPX from this point forward), which gives very high rates in ethylene methoxycarbonylation, 1b, 1l, 1o and has also been used for some other applications. 5 The potential for enantioselective hydroxycarbonylation and alkoxycarbonylation to be a useful method for large scale asymmetric synthesis has been appreciated for a long time.2-4 However, this is a challenging reaction and despite many important contributions, high enantioselectivity is rare especially for the intermolecular reaction; further research is needed. Catalysts which do give good enantioselectivity, combined with high regioselectivity in the methoxycarbonylation of styrene are Pd catalysts derived from the bulkier members of the Phanephos ligand family (shown in Scheme 1), 3,4 providing impetus to seek to evaluate and increase substrate scope for alkene carbonylation. In the literature, there are very sparse examples, even using achiral catalysts. Most examples of methoxycarbonylation of internal alkenes have led to tandem isomerisation-linear select...

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“…Recently, Klaus et al 8 have reported the cobalt-catalyzed selective hydroalkoxycarbonylation of enamides in the absence of chiral ligands. In the publication by Becker et al, 9 it is disclosed that only negligible optical yield (ca. 1%) was obtained in the asymmetric hydrocarboalkoxylation of Nvinylphthalimide.…”

Section: Introductionmentioning

confidence: 99%

Palladium‐catalyzed selective alkoxycarbonylation of N‐vinylphthalimide

Zhu

Jiang

2006

Applied Organom Chemis

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The palladium-catalyzed selective alkoxycarbonylation of enamide was studied using N-vinylphthalimide as the model substrate. Both palladium (0) and palladium (II) compounds can be used as the catalyst precursors. It was found that the efficiency and the regioselectivity of the reaction depended remarkably on phosphine ligands and other reaction parameters such as solvent, substrate concentration, temperature and promoters. Good yields and high regioselectivities of either the branched or linear products were obtained under optimum reaction conditions. The primary optical yield (12.3%) of N-Phthaloyl-L-alanine methyl ester (2) was obtained using (S)-(+)-BNPPA as the chiral ligand. A possible reaction mechanism for the alkoxycarbonylation of N-vinylphthalimide was also proposed.

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Asymmetric hydroformylation and hydrocarboxylation of enamides. Synthesis of alanine and proline

Cited by 99 publications

References 0 publications

The asymmetric hydroformylation in the synthesis of pharmaceuticals

The asymmetric hydroformylation in the synthesis of pharmaceuticals

Isomerisation versus carbonylative pathways in the hydroxy-carbonylation, methoxy-carbonylation, and amino-carbonylation of N-tosyl-3-pyrroline

Palladium‐catalyzed selective alkoxycarbonylation of N‐vinylphthalimide

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