Enantioselective α-Arylation of Aldehydes via Organo-SOMO Catalysis. An Ortho-Selective Arylation Reaction Based on an Open-Shell Pathway

Conrad, Jay C.; Kong, Jongrock; Laforteza, Brian N.; MacMillan, David W. C.

doi:10.1021/ja9026902

Cited by 241 publications

(88 citation statements)

References 18 publications

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“…The stereochemistry of (±)- 6 was unequivocally assigned by NMR data, which were consistent with those reported [35–37]. …”

Section: Resultssupporting

confidence: 90%

“…(−)-Tashiromine has been accessed through the ring closure of difunctionalized acyclic chiral sulfonamide-based β-amino acids [35], the cyclization of pyrrole derivatives with a chiral side-chain [36], or the enantioselective arylation of pyrrole, followed by saturation [37]. The transformation of chiral functionalized pyrrole or pyrrolidine derivatives has served as the basis of the construction of (−)-epitashiromine [38–39] (Fig.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Novel stereocontrolled syntheses of tashiromine and epitashiromine

Kiss¹,

Forró²,

Fülöp³

2015

Beilstein J. Org. Chem.

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“…The stereochemistry of (±)- 6 was unequivocally assigned by NMR data, which were consistent with those reported [35–37]. …”

Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Novel stereocontrolled syntheses of tashiromine and epitashiromine

Kiss¹,

Forró²,

Fülöp³

2015

Beilstein J. Org. Chem.

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“…Examples include the direct allylic alkylation (20), the α-arylation (20,25), α-enolation (26), α-vinylation (27), α-carbooxidation of alkenes (28), α-nitro alkylation en route to corresponding amino acids (29), as well as α-chlorination (30) (Scheme 4). Given the high synthetic utility of these enantioenriched aldehyde synthons, we recently recognized the importance (as well as the potential difficulties) in extending this SOMO catalysis concept to ketonic motifs.…”

Section: Enantioselective Somo Catalysismentioning

confidence: 99%

Direct and enantioselective α-allylation of ketones via singly occupied molecular orbital (SOMO) catalysis

Mastracchio

Warkentin

Walji

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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110

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The first enantioselective organocatalytic α-allylation of cyclic ketones has been accomplished via singly occupied molecular orbital catalysis. Geometrically constrained radical cations, forged from the one-electron oxidation of transiently generated enamines, readily undergo allylic alkylation with a variety of commercially available allyl silanes. A reasonable latitude in both the ketone and allyl silane components is readily accommodated in this new transformation. Moreover, three new oxidatively stable imidazolidinone catalysts have been developed that allow cyclic ketones to successfully participate in this transformation. The new catalyst platform has also been exploited in the first catalytic enantioselective α-enolation and α-carbooxidation of ketones.asymmetric synthesis | organocatalysis T he enantioselective catalytic α-alkylation of simple ketones remains a fundamental goal in chemical synthesis (1-4). Seminal work from Doyle and Jacobsen (5), Trost and co-workers (6-8), Stoltz and co-workers (9, 10), Braun and co-workers (11,12), and Hartwig and co-workers (13, 14) has introduced valuable previously undescribed technologies for (i) the enantioselective alkylation of preformed or in situ generated metal enolates (5,6,(11)(12)(13)(14)(15)(16)(17) and (ii) the asymmetric and decarboxylative conversion of allyl keto carbonates to α-allylated ketones (7-10). With these key advances in place, a goal now for asymmetric catalysis has become the direct α-allylation of simple ketone substrates (18,19), an elusive yet potentially powerful bond construction (Scheme 1).Recently, we questioned whether the catalytic principles of singly occupied molecular orbital (SOMO) activation (20) might be translated to ketonic systems, thereby providing an unreported mechanism for direct and enantioselective α-carbonyl alkylation. Despite the superficial similarities between aldehydes and ketones, these carbonyl families exhibit largely different steric and electronic properties with respect to catalyst interactions. As a consequence, the translation of enantioselective activation modes between these carbonyl subclasses is often difficult (if not unattainable in many cases) (21,22). Herein, we describe the invention of a previously undisclosed family of organocatalysts that enable cyclic ketones to successfully function within the SOMO-activation platform while being chemically robust to oxidative reagents. Moreover, we document the introduction of a previously undescribed catalytic α-ketone alkylation reaction that is immediately amenable to asymmetric induction. Enantioselective SOMO CatalysisOver the last decade, the field of enantioselective synthesis has witnessed tremendous progress in the successful implementation of small organic molecules as asymmetric catalysts. In particular, two modes of carbonyl activation by chiral secondary amines have led to the discovery of a large number of previously undescribed reactions (Scheme 2): (i) Iminium catalysis (23), wherein lowest unoccupied molecular orbital (LUMO) lowering a...

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“…To synthesize pseudopteroxazole ( 257 ) itself, a diastereoselective oxidative α-arylation of 285 was employed using MacMillan’s shown chiral imidazolidinone catalyst shown and the iron(III) oxidant [Fe(phen) 3 ][(PF 6 ) 3 ]. 338 Finally, analogous Wittig olefination completed the synthesis of (+)-pseudopteroxazole ( 257 ) in 15 total steps. From a strategic perspective, the ability to use common intermediate 278 in multiple synthesis pathways is a powerful method for accessing diverse natural product family members.…”

Section: Syntheses From the 21st Centurymentioning

confidence: 99%

Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

et al. 2017

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The pool of abundant chiral terpene building blocks (i.e. “chiral pool terpenes”) has long served as a starting point for the chemical synthesis of complex natural products, including many terpenes themselves. As inexpensive and versatile starting materials, such compounds continue to influence modern synthetic chemistry. This review highlights 21st century terpene total syntheses which themselves use small, terpene-derived materials as building blocks. An outlook to the future of research in this area is highlighted as well.

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Enantioselective α-Arylation of Aldehydes via Organo-SOMO Catalysis. An Ortho-Selective Arylation Reaction Based on an Open-Shell Pathway

Cited by 241 publications

References 18 publications

Novel stereocontrolled syntheses of tashiromine and epitashiromine

Novel stereocontrolled syntheses of tashiromine and epitashiromine

Direct and enantioselective α-allylation of ketones via singly occupied molecular orbital (SOMO) catalysis

Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

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