Boc Groups as Protectors and Directors for Ir-Catalyzed C−H Borylation of Heterocycles

Kallepalli, Venkata A.; Shi, Feng; Paul, Sulagna; Onyeozili, Edith N.; Maleczka, Robert E.; Smith, Milton R.

doi:10.1021/jo901822b

Cited by 101 publications

(93 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The borylation of heteroarenes, even in the absence of directing effects, 134,135 also occurs with strong regioselectivity. 111,136–138 Several examples illustrating this regioselectivity are shown in eq 41.…”

Section: Arene Functionalization Without Directing Groupsmentioning

confidence: 99%

Evolution of C–H Bond Functionalization from Methane to Methodology

2015

View full text Add to dashboard Cite

This Perspective presents the fundamental principles, the elementary reactions, the initial catalytic systems, and the contemporary catalysts that have converted C−H bond functionalization from a curiosity to a reality for synthetic chemists. Many classes of elementary reactions involving transition-metal complexes cleave C−H bonds at typically unreactive positions. These reactions, coupled with a separate or simultaneous functionalization process lead to products containing new C−C, C−N, and C−O bonds. Such reactions were initially studied for the conversion of light alkanes to liquid products, but they have been used (and commercialized in some cases) most often for the synthesis of the more complex structures of natural products, medicinally active compounds, and aromatic materials. Such a change in direction of research in C−H bond functionalization is remarkable because the reactions must occur at an unactivated C−H bond over functional groups that are more reactive than the C−H bond toward classical reagents. The scope of reactions that form C−C bonds or install functionality at an unactivated C−H bond will be presented, and the potential future utility of these reactions will be discussed.

show abstract

Section: Arene Functionalization Without Directing Groupsmentioning

confidence: 99%

Evolution of C–H Bond Functionalization from Methane to Methodology

2015

View full text Add to dashboard Cite

show abstract

“…The Ir I ‐catalyzed C–H borylation, developed by the groups of Smith–Malezcka and Hartwig–Miyaura,6 was adopted to furnish the desired pyrrole nucleus, which was followed by a Suzuki coupling. The tert ‐butylcarboxy (Boc) group is known to be a protector and director for Ir‐catalyzed borylations 23. Pyrrole 36 was converted into N ‐Boc‐pyrrole 4 in excellent yield.…”

Section: Resultsmentioning

confidence: 99%

Synthetic Strategies for the Synthesis and Transformation of Substituted Pyrrolinones as Advanced Intermediates for Rhazinilam Analogues

Kholod

Vallat²,

Buciumas³

et al. 2014

Eur J Org Chem

View full text Add to dashboard Cite

The biaryl core structure of rhazinilam with its fixed dihedral angle is a pivotal element for its unique in vitro cytotoxic activity. Most of the related natural products are oxidized versions of rhazinilam. Replacing the sensitive pyrrole ring by a pyrrolinone ring is the basis of our initial strategy towards rhazinilam analogues. With this goal, variants of the sequence crossed Mukaiyama aldol reaction followed by the Staudinger reaction were studied. Reacting a suitably substituted acetophenone with O‐methyl O‐trimethylsilyl ketene acetal gave pyrrolinones 8a and 8b in good to excellent yields. These intermediates could be transformed in four high‐yielding steps into the pyrrolic precursors 7a–c containing all the atoms necessary for the construction of rings A, B, and C of rhazinilam. Our studies illustrate a lack of stability of these intermediates. Alternative synthetic approaches towards this central biaryl core structure are described.

show abstract

“…Synthetic methods standardly introduce a protected analogue of a boronic acid. The preparation of pinacolyl arylboronate esters in particular has been well described, either starting from Seebach's imidazolidinone [103,104], via the Miyaura borylation of a (pseudo)halogenated phenylalanine [105][106][107][108], metal-halogen exchange [109], through direct Iridium-catalyzed borylation [110][111][112], or even Friedel-Crafts alkylation (selected examples are shown in Figure 8) [113]. Alternatively, direct synthesis of amino acids containing the MIDA-boronate ester group is also possible via Negishi coupling (not shown) [114].…”

Section: Synthesis Of Borylated Aromatic and Aliphatic Amino Acids Anmentioning

confidence: 99%

The Suzuki–Miyaura Cross-Coupling as a Versatile Tool for Peptide Diversification and Cyclization

et al. 2017

View full text Add to dashboard Cite

Abstract:The (site-selective) derivatization of amino acids and peptides represents an attractive field with potential applications in the establishment of structure-activity relationships and labeling of bioactive compounds. In this respect, bioorthogonal cross-coupling reactions provide valuable means for ready access to peptide analogues with diversified structure and function. Due to the complex and chiral nature of peptides, mild reaction conditions are preferred; hence, a suitable cross-coupling reaction is required for the chemical modification of these challenging substrates. The Suzuki reaction, involving organoboron species, is appropriate given the stability and environmentally benign nature of these reactants and their amenability to be applied in (partial) aqueous reaction conditions, an expected requirement upon the derivatization of peptides. Concerning the halogenated reaction partner, residues bearing halogen moieties can either be introduced directly as halogenated amino acids during solid-phase peptide synthesis (SPPS) or genetically encoded into larger proteins. A reversed approach building in boron in the peptidic backbone is also possible. Furthermore, based on this complementarity, cyclic peptides can be prepared by halogenation, and borylation of two amino acid side chains present within the same peptidic substrate. Here, the Suzuki-Miyaura reaction is a tool to induce the desired cyclization. In this review, we discuss diverse amino acid and peptide-based applications explored by means of this extremely versatile cross-coupling reaction. With the advent of peptide-based drugs, versatile bioorthogonal conversions on these substrates have become highly valuable.

show abstract

Boc Groups as Protectors and Directors for Ir-Catalyzed C−H Borylation of Heterocycles

Abstract: Ir-catalyzed C–H borylation is found to be compatible with Boc protecting groups. Thus, pyrroles, indoles, and azaindoles can be selectively functionalized at C–H positions β to N. The Boc group can be removed on thermolysis or left intact during subsequent transformations.

Cited by 101 publications

References 15 publications

Evolution of C–H Bond Functionalization from Methane to Methodology

Evolution of C–H Bond Functionalization from Methane to Methodology

Synthetic Strategies for the Synthesis and Transformation of Substituted Pyrrolinones as Advanced Intermediates for Rhazinilam Analogues

The Suzuki–Miyaura Cross-Coupling as a Versatile Tool for Peptide Diversification and Cyclization

Contact Info

Product

Resources

About