Dialkylammonium <i>tert</i>-Butylmethylphosphinites: Stable Intermediates for the Synthesis of P-Stereogenic Ligands

Salomó, Ernest; Prades, Amparo; Riéra, Antoni

doi:10.1021/acs.joc.7b01180

Cited by 14 publications

(6 citation statements)

References 34 publications

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“…Diisopropylammonium tertbutylmethylphosphinite borane 12 was found to be a convenient, highly crystalline and shelf-stable surrogate of 2a (Figure 2). 22 X-ray analysis showed that the increased stability arises from a tetrameric assembly with a cyclic H-bond network. Furthermore, 12 showed the same reactivity in the S N 2@P reaction with both amine nucleophiles and reducing agents.…”

Section: ■ Introductionmentioning

confidence: 99%

P-Stereogenic Amino-Phosphines as Chiral Ligands: From Privileged Intermediates to Asymmetric Catalysis

2020

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Conspectus Among chiral phosphines, P-stereogenic phosphines provide unparalleled activity and selectivity and have thus emerged as “state-of-the-art” ligands for asymmetric hydrogenation and other industrially relevant processes. However, the synthesis of this type of ligand implies lengthy multistep sequences, which are a hurdle for many laboratories. There is a lack of methods for the rapid construction of P-stereogenic phosphine ligands. In this respect, P-stereogenic synthons that can be rapidly incorporated into a given ligand scaffold are highly desirable. Over the last 10 years, our group has unveiled that P-stereogenic aminophosphines can be rapidly assembled in a convenient fashion from the corresponding primary aminophosphine and/or the corresponding phosphinous acid. Using cis-1-amino-2-indanol as chiral auxiliary, we devised a multigram synthesis of tert-butylmethylaminophosphine borane and tert-butylmethylphosphinous acid borane, which are key intermediate synthons. Primary aminophosphine works as nucleophilic intermediates at nitrogen. From this synthon, aminodiphosphine (MaxPHOS) and secondary imino phosphoranes (SIP) ligands were synthesized. These ligands exhibit a tautomeric equilibrium between the PH and NH forms, and because of that, they do not undergo oxidation in air. NH/PH tautomerism does not jeopardize their configurational stability, and most importantly, in the presence of a metal source, the equilibrium is shifted toward the NH form, thus allowing coordination through phosphorus. Rh-MaxPHOS and Rh-SIP complexes have been used in asymmetric hydrogenation and [2 + 2 + 2] cycloaddition reactions with outstanding results. On the other hand, P-stereogenic phosphinous acid, upon activation, serves as an electrophilic reagent with amine nucleophiles, allowing SN2 reactions at phosphorus with complete inversion of configuration. This coupling technology exhibits a great potential because it allows the incorporation of the P*-phosphine fragment in numerous ligand structures, provided there is an amino group with which to react. In a mild and efficient process, phosphinous acid has been coupled to hydrazine to yield C 2 diphosphines and to chiral benzoimidazole-amines to yield P-stereogenic benzoimidazole-phosphine ligands. The most powerful ligand system, however, arises from the condensation of three independent fragments: our phosphinous acid borane, an amino acid, and an amino alcohol, which yields a library of phosphino-oxazoline ligands named MaxPHOX. The corresponding Ir-MaxPHOX catalyst library was applied with excellent results in the asymmetric hydrogenation of α,β-unsaturated esters, 2-aryl allyl phthalimides, unfunctionalized tetrasubstituted alkenes, cyclic enamides, and N-aryl and N-methyl imines. It also has found application in asymmetric isomerization of alkenes. Overall, we developed key P-stereogenic building blocks that can be incorporated stereospecifically to ligand scaffolds and demonstrated that integration of the P*-aminophosphine fragment in a given catalytic system p...

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Section: ■ Introductionmentioning

confidence: 99%

P-Stereogenic Amino-Phosphines as Chiral Ligands: From Privileged Intermediates to Asymmetric Catalysis

2020

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“…To this end, ten new phosphinites were prepared from a stable salt of 1a in excellent yield. 13 See the Supporting Information section for the details of the synthesis and a complete list of phosphinite derivatives. With the new phosphinites in hand, we tested them for deprotection with DABCO in degassed C 6 D 6 and analyzed the conversion by 31 P NMR.…”

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confidence: 64%

“…At this point, a phosphinite derivative that could be efficiently deprotected under basic conditions was needed. To this end, ten new phosphinites were prepared from a stable salt of 1a in excellent yield . See the Supporting Information section for the details of the synthesis and a complete list of phosphinite derivatives.…”

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confidence: 70%

BOM-Phosphinite as an Electrophilic P-Stereogenic Transfer Reagent for the Synthesis of Bulky Phosphines: Synthesis of tert-Butyl(3,5-di-tert-butylphenyl)BisP*

Rojo

Riéra

2021

Org. Lett.

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BOM-tert-butylmethylphosphinite borane is an efficient electrophilic P-stereogenic transfer reagent for the synthesis of bulky tertiary phosphines. The novel methodology relies on a one-pot deprotection/substitution on the trivalent phosphinite that takes place with very high stereospecificity. The potential of this strategy is demonstrated with the synthesis of a wide scope of tertiary phosphines in excellent enantiomeric excess. The methodology was applied to the synthesis of a bulky P-stereogenic BisP* ligand analogue.

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“…With the pure imidazole amines 4 and 7 in hand we proceeded to couple them with the chiral phosphorus synthon. As we have recently reported, 17 pure tertbutylmethylphosphinous acid borane 1 has limited stability, while the corresponding dialkylammonium salts are shelf-stable crystalline solids that can be stored indefinitely.…”

Section: Introductionmentioning

confidence: 87%

Iridium complexes with P-stereogenic phosphino imidazole ligands: Synthesis, structure and catalysis

2019

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The synthesis of optically and diastereomerically pure P-stereogenic phosphine-imidazole ligands is reported. The new ligands contain either a benzoimidazole or a 4-phenylimidazole as a N-donor fragment. The ligands have been coordinated to iridium and the structure of the corresponding cationic COD complexes has been determined by X-ray analysis. The combination of the chiral phosphorus atom and the imidazole substituents generate a strong chiral environment around the metal 2 center. Preliminary hydrogenation reactions with a model cyclic -enamide are also reported. RESULTS AND DISCUSSIONLigand Synthesis. Phosphino imidazole ligands have been synthetized according to the retrosynthetic analysis shown in Scheme 1. Condensation of valine with orthophenylenendiamine and 2-bromoacetophenone should provide the corresponding chiral protected benzo-and 4-phenylimidazole amines. N-Alkylation and Boc deprotection would provide the corresponding primary amines. These will be coupled with either enantiomer of the optically pure tert-butylmethylphosphinous acid borane in a SN2 reaction at the stereogenic P-center (SN2@P) to afford the desired ligands. Scheme 1: Retrosynthetic plan for the synthesis of phosphino imidazole ligands. The synthesis of free (R)-2-methyl-1-(1-methylbenzoimidazol-2-yl)propan-1-amine 4 was conducted as shown in Scheme 2. Condensation of N-Boc valine with orthophenylenendiamine was carried out through a two-step procedure as described in the literature. 15 Isobutyl chlorocarbonate-mediated amide coupling and cyclization with AcOH at 65 ºC provided the desired N-Boc protected benzoimidazole 2 in 54% yield. Next, N-methylation of the benzoimidazole heterocycle was carried selectively with MeI and NaOH pellets in acetonitrile. This cleanly afforded 3 in 90% yield. Finally, Boc deprotection was performed in MeOH/HCl(aq) which afforded the desired benzoimidazole amine 4 in excellent yield and purity.

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Dialkylammonium tert-Butylmethylphosphinites: Stable Intermediates for the Synthesis of P-Stereogenic Ligands

Cited by 14 publications

References 34 publications

P-Stereogenic Amino-Phosphines as Chiral Ligands: From Privileged Intermediates to Asymmetric Catalysis

P-Stereogenic Amino-Phosphines as Chiral Ligands: From Privileged Intermediates to Asymmetric Catalysis

BOM-Phosphinite as an Electrophilic P-Stereogenic Transfer Reagent for the Synthesis of Bulky Phosphines: Synthesis of tert-Butyl(3,5-di-tert-butylphenyl)BisP*

Iridium complexes with P-stereogenic phosphino imidazole ligands: Synthesis, structure and catalysis

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