Enantioselective synthesis of gem-disubstituted N-Boc diazaheterocycles via decarboxylative asymmetric allylic alkylation

Sun, Alexander W.; Hess, Stephan N.; Stoltz, Brian M.

doi:10.1039/c8sc03967d

Cited by 30 publications

(20 citation statements)

References 39 publications

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“…These issues were addressed by the Stoltz group in a recent publication reporting a new 3-step sequence beginning from commercially available 1-Boc-3-oxopiperazine. 591 As part of this work, the application of an isomeric substrate class, N -Boc tetrahydropyrimidin-2-ones was described ( Scheme 217 ). The desired α-quaternary products were formed in excellent yields and ee values of up to 95%.…”

Section: Asymmetric Decarboxylative Allylic Substitutionmentioning

confidence: 99%

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

Pàmies

Margalef

Cañellas³

et al. 2021

Chem. Rev.

411

202

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This Review compiles the evolution, mechanistic understanding, and more recent advances in enantioselective Pd-catalyzed allylic substitution and decarboxylative and oxidative allylic substitutions. For each reaction, the catalytic data, as well as examples of their application to the synthesis of more complex molecules, are collected. Sections in which we discuss key mechanistic aspects for high selectivity and a comparison with other metals (with advantages and disadvantages) are also included. For Pd-catalyzed asymmetric allylic substitution, the catalytic data are grouped according to the type of nucleophile employed. Because of the prominent position of the use of stabilized carbon nucleophiles and heteronucleophiles, many chiral ligands have been developed. To better compare the results, they are presented grouped by ligand types. Pd-catalyzed asymmetric decarboxylative reactions are mainly promoted by PHOX or Trost ligands, which justifies organizing this section in chronological order. For asymmetric oxidative allylic substitution the results are grouped according to the type of nucleophile used.

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Section: Asymmetric Decarboxylative Allylic Substitutionmentioning

confidence: 99%

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

Pàmies

Margalef

Cañellas³

et al. 2021

Chem. Rev.

411

202

View full text Add to dashboard Cite

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“…In 2019, the Stoltz group developed an improved Pd-catalyzed DAAA reaction for the synthesis of unprecedented chiral ,-disubstituted piperazin-2-ones and tetrahydropyrimidin-2-ones (Scheme 5). 33 Their previous study indicated that the N-protecting groups were crucial for the DAAA reaction and further elaboration. In this case, using N4-Boc (tert-butoxycarbonyl) protected piperazin-2-ones and tetrahydropyrimidin-2-ones as substrates, a variety of asymmetric alkylation products were obtained in good yield and ee in the presence of (S)-(CF 3 ) 3 -t-BuPHOX and Pd 2 (pmdba) 3 .…”

Section: Scheme 4 Synthesis Of Nitroalkanes From Allyl Nitroestersmentioning

confidence: 99%

Recent Advances in the Construction of Quaternary Stereocenters via Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

Zhang

Liu

et al. 2021

Synthesis

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Palladium catalyzed decarboxylative asymmetric allylic alkylation (DAAA) provides an efficient and powerful strategy to construct quaternary stereocenters which are widely present in biologically active natural products and approved drugs. In this short review, we summarize recent developments (since 2018) in the facile synthesis of quaternary stereocenters via DAAA methods. Several representative examples by using DAAA strategy for total synthesis of complex natural products further demonstrate its synthetic potential in the realm of organic and medicinal chemistry

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“…Standing on the success of the catalytic asymmetric synthesis of N ‐Boc‐piperazin‐2‐ones, Stoltz developed an enantioselective allylation with isomeric substrates, N ‐Boc‐tetrahydropyrimidin‐5‐ones in 2019 (Scheme ) . Under optimized conditions, a broad range of substituents were introduced at the α‐position in high enantioselectivities.…”

Section: C(α)–h/r Bond Formationmentioning

confidence: 99%

Recent Advances in the Catalytic Asymmetric Synthesis of β²‐ and β^2,2‐Amino Acids

Noda

Shibasaki

2019

Eur J Org Chem

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The importance of -amino acids for peptidomimetics and their presence in numerous natural products and pharmaceuticals make the development of the corresponding synthetic procedures a task of high practical significance. Herein, we focus on the recent developments in the catalytic asymmetric synthesis of 2 -and 2,2 -amino acids. The examples are arranged according to strategic bond disconnections. Despite the abundance of feasible approaches, only a handful of reaction [a] Dr. 2350 types can effectively furnish 2 -and 2,2 -amino acid derivatives with sufficient enantioselectivity suitable for peptide applications. These include asymmetric hydrogenation or conjugate addition of acrylates, α-functionalization of -amino acid enolate precursors, and aminomethylation of carbonyl compounds. Hence, future research directions are discussed considering these literature precedents.fied so far, -peptides -oligomers of -amino acids -have attracted considerable attention due to their structural similarity to native α-peptides and the conformational rigidity and chemical stability bestowed by the unnatural residues. [2] Contemporary research has further diverged into the use of γ-amino acids and α/ -hybrid peptides. [3] -Amino acids are also found in many natural products and pharmaceutical agents such as -lactams, [4] rendering the development of corresponding synthetic procedures an important task of synthetic organic chemistry.-Amino acids are homologated variants of α-amino acids, which are structurally categorized by their side-chain substitution patterns. The nomenclature for -amino acids is as follows: 3 denotes those with a substituent at the -position, 2 at the α-position, 2,3 at both αand -positions, and so on (Figure 1). Cyclic -amino acids are also classified in a similar fashion. 3 -Amino acids can be synthesized from the corresponding Minireview 2352 Scheme 3. Rh-catalyzed enantioselective hydrogenation of -phthalimide acrylates 5 reported by Zheng. Scheme 4. Rh-catalyzed enantioselective hydrogenation of (α-aminomethyl)acrylates 7 reported by Qiu. Scheme 16. Organocatalytic asymmetric conjugate addition of pyrrolidin-2,3dione 30 for the synthesis of 2,2 -peptidic compounds reported by Palomo.acid derivative 33, followed by the asymmetric protonation of the resulting enolate of the 5-membered ring to afford 4-substituted isoxazolidin-5-ones 35 (Scheme 17). [49] Although the selectivities need further improvement for practical applications, this work is one of the rare examples of the synthesis of 2 -amino acids bearing functionalized side chains (e.g., 35d).Scheme 17. Organocatalytic asymmetric protonation for the synthesis of 4-substituted isoxazolidin-5-ones 35 reported by Brière.

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Enantioselective synthesis of gem-disubstituted N-Boc diazaheterocycles via decarboxylative asymmetric allylic alkylation

Abstract: An enantioselective synthesis of diverse N4-Boc-protected α,α-disubstituted piperazin-2-ones and tetrahydropyrimidin-2-ones using the palladiumcatalyzed decarboxylative allylic alkylation reaction has been achieved.

Cited by 30 publications

References 39 publications

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

Recent Advances in the Construction of Quaternary Stereocenters via Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

Recent Advances in the Catalytic Asymmetric Synthesis of β²‐ and β^2,2‐Amino Acids

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Enantioselective synthesis of gem-disubstituted N-Boc diazaheterocycles via decarboxylative asymmetric allylic alkylation

Abstract: An enantioselective synthesis of diverse N4-Boc-protected α,α-disubstituted piperazin-2-ones and tetrahydropyrimidin-2-ones using the palladiumcatalyzed decarboxylative allylic alkylation reaction has been achieved.

Cited by 30 publications

References 39 publications

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

Recent Advances in the Construction of Quaternary Stereocenters via Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

Recent Advances in the Catalytic Asymmetric Synthesis of β2‐ and β2,2‐Amino Acids

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Recent Advances in the Catalytic Asymmetric Synthesis of β²‐ and β^2,2‐Amino Acids