Rhodium-Catalyzed Enantioselective Anti-Markovnikov Hydroformylation of α-Substituted Acryl Acid Derivatives

Li, Shuailong; Li, Zhuangxing; You, Cai; Li, Xiuxiu; Yang, Jiaxin; Lv, Hui; Zhang, Xumu

doi:10.1021/acs.orglett.9b04624

Cited by 23 publications

(15 citation statements)

References 48 publications

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“…Asymmetric hydroformylation (AHF) represents an efficient approach for asymmetric formation of C–C bond in an atomic economic manner 17 – 25 , and the aldehyde products can be easily converted to versatile functional compounds, such as chiral alcohols, acids, amines and esters 26 – 34 , thus AHF has been widely investigated and some significant progresses have been made 35 – 45 . However, most of the work focused on the AHF of monosubstituted olefins and disubstituted alkenes, and only one chiral center was introduced into the product.…”

Section: Introductionmentioning

confidence: 99%

A concise access to bridged [2,2,1] bicyclic lactones with a quaternary stereocenter via stereospecific hydroformylation

et al. 2021

Nat Commun

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Chiral bridged [2,2,1] bicyclic lactones are privileged structural units in pharmaceutics and bioactive nature products. However, the synthetic methods for these compounds are rare. Here we report an efficient method for enantioselective construction of bridged [2,2,1] bicyclic lactones bearing a quaternary stereocenter via Rh-catalyzed asymmetric hydroformylation/intramolecular cyclization/pyridium chlorochromate (PCC) oxidation. By employing a hybrid phosphine-phosphite chiral ligand, a series of cyclopent-3-en-1-ols are transformed into corresponding γ-hydroxyl aldehydes with specific syn-selectivity. Then, hemiacetals form in situ and oxidation with PCC in one-pot affords bridged [2,2,1] bicyclic lactones in high yields and excellent enantiomeric excess. Replacing the hydroxyl group by an ester group, cyclopentanecarbaldehydes with a chiral all-carbon quaternary stereocenter in the γ-position can be generated efficiently.

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Section: Introductionmentioning

confidence: 99%

A concise access to bridged [2,2,1] bicyclic lactones with a quaternary stereocenter via stereospecific hydroformylation

et al. 2021

Nat Commun

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“…The most recent contribution in the AHF of α-substituted acrylates has been made by Zhang and co-workers with a phosphine-phosphoroamide ligand from the (S,S)-YanPhos family (15). This ligand family was previously successfully applied on the AHF of 1,1 0 -disubstituted alkenes with weakly coordinative groups (16) and without coordinative groups (17) providing high activities and selectivities (see in Section 4).…”

Section: N-selective Asymmetric Hydroformylationmentioning

confidence: 99%

“…Indeed, only a few examples were reported in the asymmetric hydroformylation of nonsubstituted acrylamides with moderate yields and enantioselectivities (18). The only two existing publications reporting the AHF of α-substituted acrylamides appeared in 2020 (15,19). In one of them, only three substrates were studied.…”

Section: N-selective Asymmetric Hydroformylationmentioning

confidence: 99%

Evolution in the metal-catalyzed asymmetric hydroformylation of 1,1′-disubstituted alkenes

Margalef

Langlois

Garcia

et al. 2021

Advances in Catalysis

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“…It should, however, be noted that engaging such alkenes could open up direct access to valuable β-chiral linear aldehydes . A plethora of 1,1-disubstituted alkenes bearing different functional groups have become notable candidates in efficient AHF reactions . However, respectable enantioselectivities with unfunctionalized 1,1-disubstituted alkenes remained a formidable task for a long time.…”

Section: Introductionmentioning

confidence: 99%

Unraveling the Importance of Noncovalent Interactions in Asymmetric Hydroformylation Reactions

2020

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For catalytic asymmetric hydroformylation (AHF) of alkenes to chiral aldehydes, though a topic of high interest, the contemporary developments remain largely empirical owing to rather limited molecular insights on the origin of enantioselectivity. Given this gap, herein, we present the mechanistic details of Rh-(S,S)-YanPhoscatalyzed AHF of α-methylstyrene, as obtained through a comprehensive DFT (ω-B97XD and M06) study. The challenges with the double axially chiral YanPhos, bearing an N-benzyl BINOL-phosphoramidite and a BINAP-bis(3,5-t-Bu-aryl)phosphine, are addressed through exhaustive conformational sampling. The C−H•••π, π•••π, and lone pair•••π noncovalent interactions (NCIs) between the N-benzyl and the rest of the chiral ligand limit the N-benzyl conformers. Similarly, the C−H•••π and π•••π NCIs between the chiral catalyst and α-methylstyrene render the siface binding to the Rh-center more preferred over the re-face. The transition state (TS) for the regiocontrolling migratory insertion, triggered by the Rh-hydride addition to the alkene, to the more substituted α-carbon is 3.6 kcal/mol lower than that to the β-carbon, thus favoring the linear chiral aldehyde over the achiral branched alternative. In the linear pathway, the TS for the hydride addition to the si-face is 1.5 kcal/mol lower than that to the re-face, with a predicted ee of 85% for the S aldehyde (expt. 87%). The energetic span analysis reveals the reductive elimination as the turnover determining step for the preferred S linear aldehyde. These molecular insights could become valuable for exploiting AHF reactions for substituted alkenes and for eventual industrial implementation.

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Rhodium-Catalyzed Enantioselective Anti-Markovnikov Hydroformylation of α-Substituted Acryl Acid Derivatives

Cited by 23 publications

References 48 publications

A concise access to bridged [2,2,1] bicyclic lactones with a quaternary stereocenter via stereospecific hydroformylation

A concise access to bridged [2,2,1] bicyclic lactones with a quaternary stereocenter via stereospecific hydroformylation

Evolution in the metal-catalyzed asymmetric hydroformylation of 1,1′-disubstituted alkenes

Unraveling the Importance of Noncovalent Interactions in Asymmetric Hydroformylation Reactions

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