How Big is the Pinacol Boronic Ester as a Substituent?

Fasano, Valerio; McFord, Aidan W.; Collins, Beatrice S. L.; Fey, Natalie; Alder, Roger W.; Aggarwal, Varinder K.

doi:10.1002/anie.202007776

“…Usually, α-substituted allylboron compounds with bulky protecting groups (e.g., pinacol or 9-BBN) react with poor E / Z selectivity in allylboration reactions. 42 , 43 …”

mentioning

confidence: 99%

Organocatalytic Synthesis of α-Trifluoromethyl Allylboronic Acids by Enantioselective 1,2-Borotropic Migration

Jonker

¹

,

Jayarajan

²

,

Kireilis

³

et al. 2020

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Chiral α-substituted allylboronic acids were synthesized by asymmetric homologation of alkenylboronic acids using CF 3 /TMS-diazomethanes in the presence of BINOL catalyst and ethanol. The chiral α-substituted allylboronic acids were reacted with aldehydes or oxidized to alcohols in situ with a high degree of chirality transfer. The oxygen-sensitive allylboronic acids can be purified via their isolated diaminonaphthalene (DanH)-protected derivatives. The highly reactive purified allylboronic acids reacted in a self-catalyzed reaction at room temperature with ketones, imines, and indoles to give congested trifluoromethylated homoallylic alcohols/amines with up to three contiguous stereocenters.

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“…Currently, the only limitation for this methodology ( Figure 3C) was found when attempting the cyclization of substrates with a small R 1 group (e.g. R 1 =H, 40) and when R 1 = Bpin (41) 46 .…”

Section: Figure 2 Cyclization Optimization To Access Bcpsmentioning

confidence: 99%

“…For example, the oxidation of Additionally, 20 was subjected to Zweifel olefination 47,48 , Aggwaral's arylation protocol 49 , and Matteson homologation 50 to afford C-C bond-forming products 43, 44 and 45, respectively. The Bpin group can also be transformed to the more stable trifluoroborate salt (46), which opens further functionalization opportunities. Radical proto-deborylation 51 results in C1, C2-disubstitued BCPs (47), and C(sp 3 )-C(sp 2 ) Pd catalyzed Suzuki cross-coupling conditions 52,53 enables arylation at the bridge head (48).…”

Section: Figure 2 Cyclization Optimization To Access Bcpsmentioning

confidence: 99%

Synthesis of Multi-Substituted Bicycloalkyl Boronates: An Intramolecular Coupling Approach to Alkyl Bioisosteres

Yang¹,

Tsien²,

Hughes³

et al. 2021

Preprint

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Bicyclic hydrocarbons, bicyclo[1.1.1]pentanes (BCPs) in particular, play an emerging role as saturated bioisosteres in pharmaceutical, agrochemical, and material chemistry. Taking advantage of strain release strategies, prior synthetic studies have featured the synthesis of bridgehead-substituted (C1, C3) BCPs from [1.1.1]propellane. This work describes a novel approach to accessing multi-substituted BCPs via a new type of intramolecular cyclization. In addition to the C1, C3-disubstituted BCPs, this method also enables the construction of yet underexplored tri-substituted (C1, C2 and C3) BCPs from readily accessible cyclobutanones. The broad generality of this cyclization is examined through synthesis of a variety of caged bicyclic molecules, ranging from [1.1.1] to [3.2.1] scaffolds. The modularity afforded by the pendant bridgehead Bpin resulted from the cyclization is demonstrated via several downstream functionalizations, highlighting the ability of this approach for programmed and divergent synthesis of multi-substituted bicyclic hydrocarbons.

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“…Additionally, 20 was subjected to Zweifel olefination 47,48 , Aggwaral's arylation protocol 49 , and Matteson homologation 50 to afford C-C bond-forming products 43, 44 and 45, respectively. The Bpin group can also be transformed to the more stable trifluoroborate salt (46), which opens further functionalization opportunities. Radical proto-deborylation 51 results in C1, C2-disubstitued BCPs (47), and C(sp 3 )-C(sp 2 ) Pd catalyzed Suzuki cross-coupling conditions 52,53 enables arylation at the bridge head (48).…”

Section: Figure 2 Cyclization Optimization To Access Bcpsmentioning

confidence: 99%

Synthesis of Multi-Substituted Bicycloalkyl Boronates: An Intramolecular Coupling Approach to Alkyl Bioisosteres

Yang¹,

Tsien²,

Hughes³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

Bicyclic hydrocarbons, bicyclo[1.1.1]pentanes (BCPs) in particular, play an emerging role as saturated bioisosteres in pharmaceutical, agrochemical, and material chemistry. Taking advantage of strain release strategies, prior synthetic studies have featured the synthesis of bridgehead-substituted (C1, C3) BCPs from [1.1.1]propellane. This work describes a novel approach to accessing multi-substituted BCPs via a new type of intramolecular cyclization. In addition to the C1, C3-disubstituted BCPs, this method also enables the construction of yet underexplored tri-substituted (C1, C2 and C3) BCPs from readily accessible cyclobutanones. The broad generality of this cyclization is examined through synthesis of a variety of caged bicyclic molecules, ranging from [1.1.1] to [3.2.1] scaffolds. The modularity afforded by the pendant bridgehead Bpin resulted from the cyclization is demonstrated via several downstream functionalizations, highlighting the ability of this approach for programmed and divergent synthesis of multi-substituted bicyclic hydrocarbons.

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How Big is the Pinacol Boronic Ester as a Substituent?

Cited by 42 publications

References 43 publications

Organocatalytic Synthesis of α-Trifluoromethyl Allylboronic Acids by Enantioselective 1,2-Borotropic Migration

Organocatalytic Synthesis of α-Trifluoromethyl Allylboronic Acids by Enantioselective 1,2-Borotropic Migration

Synthesis of Multi-Substituted Bicycloalkyl Boronates: An Intramolecular Coupling Approach to Alkyl Bioisosteres

Synthesis of Multi-Substituted Bicycloalkyl Boronates: An Intramolecular Coupling Approach to Alkyl Bioisosteres

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