Stereospecific 1,2‐Migrations of Boronate Complexes Induced by Electrophiles

Wang, Hui; Jing, Changcheng; Noble, Adam; Aggarwal, Varinder K.

doi:10.1002/anie.202008096

“…The diastereoselectivity observed in the synthesis of octahydroindoles 10 and octahydrocyclopenta[ b ]pyrroles 13 can be also rationalized in agreement with the mechanistic proposal, and considering 1) a diastereoselective carboborylation of the diazo compound, [28, 29] 2) a stereoretentive carboborylation of the azide. Retention of configuration on the latter step is expected considering that 1,2‐migrations of boronate complexes are stereospecific and proceed with retention of configuration on the migrating group [17a, 20, 30] . Therefore we propose that the stereochemistry must be defined in the first step.…”

Section: Resultsmentioning

confidence: 93%

Synthesis of Pyrrolidines by a Csp³‐Csp³/Csp³‐N Transition‐Metal‐Free Domino Reaction of Boronic Acids with γ‐Azido‐N‐Tosylhydrazones

Florentino

¹

,

López

²

,

Barroso

³

et al. 2020

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The reaction between g-azido-N-tosylhydrazones and boronic acids leads to the obtention of 2,2-disubstituted pyrrolidines in adomino process that includes 1) diazoalkane formation, 2) intermolecular carboborylation of the diazocompound, and 3) intramolecular carborylation of the azide, and comprises the formation of aC sp 3 À Csp 3 and aC sp 3 À N bonds on the same carbon atom. The reaction proceeds without the need of any transition-metal catalyst under microwave activation and features wide scope in both reaction partners.It can be applied to both alkyla nd arylboronic acids with equal efficiency.W ith N-tosylhydrazones derived from 2-(2-azidoethyl)-cyclopentanone and cyclohexanone the reactions are highly diastereoselective leading to the cis-fused bicyclic systems as unique diastereoisomers.T he scope of the process is illustrated by over sixty examples,including scaffolds present in natural alkaloids,and the mechanistic proposal is suppported by DFT-based computations.

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“…With these observations in hand, we extended the reaction to a variety of aldehydes and boronic acids (Scheme 3). Keeping 2 a as the reaction partner, we observed that the reaction was very general for the aldehyde counterpart (Scheme 3 a), tolerating other a-hetero functionalized aldehydes (7-9) that included the acid-labile TBSO group (7) and a proline derivative (9) that reacted without epimerization (see SI), [24] 1,2-dicarbonyl derivatives (10, 11), a,b-unsaturated aldehydes (12,13), aliphatic aldehydes (14-16) and aromatic aldehydes (6,(17)(18)(19)(20)(21) including examples with electron-donor substituents (17,18), ortho-substitution (18), and electron-accepting substituents (19)(20)(21). a-Hetero functionalized (4, 7, 8) aldehydes reacted with 2 a at rt allowing the synthesis of the corresponding ketones in good yields.…”

mentioning

confidence: 90%

“…The ability of boronates to engage in migration reactions triggered by the presence of a nearby electrophilic site is one of the most relevant reactions in boron chemistry. [18] In particular, the activation of boronic acids with oxygen nucleophiles permits the transformation of a-hydroxyaldehydes into amines (the Petasis-Mannich reaction). [19] In this reaction, coordination of a vinyl or aryl boronic acid to the hydroxy moiety generates a boronate intermediate that intermolecularly transfers its carbon group to the electrophilic iminium species formed by the interaction of the aldehyde with a primary or secondary amine (Scheme 1 d).…”

mentioning

confidence: 99%

Synthesis of Ketones by C−H Functionalization of Aldehydes with Boronic Acids under Transition‐Metal‐Free Conditions

Roscales

¹

,

Csákÿ

²

2021

Angewandte Chemie

1

0

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A method for the synthesis of ketones from aldehydes and boronic acids via a transition-metal-free C À H functionalization reaction is reported. The method employs nitrosobenzene as a reagent to drive the simultaneous activation of the boronic acid as a boronate and the activation of the C À H bond of the aldehyde as an iminium species that triggers the key C À C bond-forming step via an intramolecular migration from boron to carbon. These findings constitute a practical, scalable, and operationally straightforward method for the synthesis of ketones. Ketones are important structural motifs [1] and building blocks [2] in organic chemistry (Scheme 1 a). Despite the many reactions available for their synthesis (e.g. reaction of carboxylic acid derivatives with organometallic reagents, transition-metal-catalyzed cross-couplings, Friedel-Crafts or Mannich reactions), [3, 4] there is a continuous need for the development of new ways to improve their preparation in search of rapid methods that use readily available starting materials. This is the case of the C À H functionalization of aldehydes (Scheme 1 b), that is, the replacement of their C(sp 2)ÀH bond for a C(sp 2)ÀC bond. [5] For this reaction to be highly efficient, it is imperative to find friendly-to-use reagents and avoid the use of toxic metals, cumbersome additives, or harsh reaction conditions. Aldehydes have been used profusely as starting materials for the synthesis of ketones. Aside from the classic two-step procedure that consists of the addition of a carbon nucleophile, for example, a Grignard reagent, followed by the oxidation of the intermediate secondary alcohol, [6] aldehydes have been converted to ketones by making use of umpolung reactions that render acyl anion equivalents. [7, 8] More recently, the use of acyl radicals, [9] carbonyl Heck reactions [10] and other related transition-metal-catalyzed additions [11] as well as hydroacylation reactions [12] have been gaining popularity for the direct synthesis of ketones from aldehydes. However, most of these methods rely on the use of strong bases, transition-metals, ancillary ligands, or harsh reaction conditions. Also, many of them are restricted to a particular type of aldehyde, either aliphatic or aromatic. We became interested in exploiting the reaction between aldehydes and nitrosobenzene [13] (Scheme 1 c) in connection with previous research concerning new reactions that involve boronic acids and nitroso compounds. [14] Boronic acids are well known for their ability to act as bench-stable carbon nucleophiles. [15] Due to their low reactivity, [16] they have mostly been used in combination with transition-metals. C À C bond formation using boronic acids as reagents under transition-metal-free conditions is comparatively rare. [17] Scheme 1. A) Synthetic utility of ketones. B) Synthesis of ketones from aldehydes. C) Reaction intermediates in the formation of hydroxamic acids from aldehydes and nitrosobenzene. D) Typical mechanism of the Petasis-Mannich reaction. E) C(sp 2)-H aldehyde activatio...

show abstract

“…With these observations in hand, we extended the reaction to a variety of aldehydes and boronic acids (Scheme 3). Keeping 2 a as the reaction partner, we observed that the reaction was very general for the aldehyde counterpart (Scheme 3 a), tolerating other a-hetero functionalized aldehydes (7)(8)(9) that included the acid-labile TBSO group 7and a proline derivative (9) that reacted without epimerization (see SI), [24] 1,2-dicarbonyl derivatives (10,11), a,b-unsaturated aldehydes (12,13), aliphatic aldehydes (14-16) and aromatic aldehydes (6,(17)(18)(19)(20)(21) including examples with electron-donor substituents (17,18), ortho-substitution 18, and electron-accepting substituents (19)(20)(21). a-Hetero functionalized (4,7,8) aldehydes reacted with 2 a at rt allowing the synthesis of the corresponding ketones in good yields.…”

mentioning

confidence: 98%

“…More hindered (5,9,16) and a,b-unsaturated aldehydes (12,13) also reacted at rt but in moderate yields, which were increased upon heating. However, aromatic aldehydes (6,(17)(18)(19)(20)(21) and 1,2-dicarbonyl derivatives (10,11) required the reaction to be performed at 110 8C. To demonstrate the potential synthetic utility of this methodology, two of the examples (4 and 6) were executed on a 1 g scale with similar yields (see the Supporting Information for details).…”

mentioning

confidence: 99%

Synthesis of Ketones by C−H Functionalization of Aldehydes with Boronic Acids under Transition‐Metal‐Free Conditions

Roscales

¹

,

Csákÿ

²

2021

Angew Chem Int Ed

6

0

View full text Add to dashboard Cite

A method for the synthesis of ketones from aldehydes and boronic acids via a transition-metal-free C À H functionalization reaction is reported. The method employs nitrosobenzene as a reagent to drive the simultaneous activation of the boronic acid as a boronate and the activation of the C À H bond of the aldehyde as an iminium species that triggers the key C À C bond-forming step via an intramolecular migration from boron to carbon. These findings constitute a practical, scalable, and operationally straightforward method for the synthesis of ketones. Ketones are important structural motifs [1] and building blocks [2] in organic chemistry (Scheme 1 a). Despite the many reactions available for their synthesis (e.g. reaction of carboxylic acid derivatives with organometallic reagents, transition-metal-catalyzed cross-couplings, Friedel-Crafts or Mannich reactions), [3, 4] there is a continuous need for the development of new ways to improve their preparation in search of rapid methods that use readily available starting materials. This is the case of the C À H functionalization of aldehydes (Scheme 1 b), that is, the replacement of their C(sp 2)ÀH bond for a C(sp 2)ÀC bond. [5] For this reaction to be highly efficient, it is imperative to find friendly-to-use reagents and avoid the use of toxic metals, cumbersome additives, or harsh reaction conditions. Aldehydes have been used profusely as starting materials for the synthesis of ketones. Aside from the classic two-step procedure that consists of the addition of a carbon nucleophile, for example, a Grignard reagent, followed by the oxidation of the intermediate secondary alcohol, [6] aldehydes have been converted to ketones by making use of umpolung reactions that render acyl anion equivalents. [7, 8] More recently, the use of acyl radicals, [9] carbonyl Heck reactions [10] and other related transition-metal-catalyzed additions [11] as well as hydroacylation reactions [12] have been gaining popularity for the direct synthesis of ketones from aldehydes. However, most of these methods rely on the use of strong bases, transition-metals, ancillary ligands, or harsh reaction conditions. Also, many of them are restricted to a particular type of aldehyde, either aliphatic or aromatic. We became interested in exploiting the reaction between aldehydes and nitrosobenzene [13] (Scheme 1 c) in connection with previous research concerning new reactions that involve boronic acids and nitroso compounds. [14] Boronic acids are well known for their ability to act as bench-stable carbon nucleophiles. [15] Due to their low reactivity, [16] they have mostly been used in combination with transition-metals. C À C bond formation using boronic acids as reagents under transition-metal-free conditions is comparatively rare. [17] Scheme 1. A) Synthetic utility of ketones. B) Synthesis of ketones from aldehydes. C) Reaction intermediates in the formation of hydroxamic acids from aldehydes and nitrosobenzene. D) Typical mechanism of the Petasis-Mannich reaction. E) C(sp 2)-H aldehyde activatio...

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Stereospecific 1,2‐Migrations of Boronate Complexes Induced by Electrophiles

Cited by 118 publications

References 84 publications

Synthesis of Pyrrolidines by a Csp³‐Csp³/Csp³‐N Transition‐Metal‐Free Domino Reaction of Boronic Acids with γ‐Azido‐N‐Tosylhydrazones

Synthesis of Pyrrolidines by a Csp³‐Csp³/Csp³‐N Transition‐Metal‐Free Domino Reaction of Boronic Acids with γ‐Azido‐N‐Tosylhydrazones

Synthesis of Ketones by C−H Functionalization of Aldehydes with Boronic Acids under Transition‐Metal‐Free Conditions

Synthesis of Ketones by C−H Functionalization of Aldehydes with Boronic Acids under Transition‐Metal‐Free Conditions

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Stereospecific 1,2‐Migrations of Boronate Complexes Induced by Electrophiles

Cited by 118 publications

References 84 publications

Synthesis of Pyrrolidines by a Csp3‐Csp3/Csp3‐N Transition‐Metal‐Free Domino Reaction of Boronic Acids with γ‐Azido‐N‐Tosylhydrazones

Synthesis of Pyrrolidines by a Csp3‐Csp3/Csp3‐N Transition‐Metal‐Free Domino Reaction of Boronic Acids with γ‐Azido‐N‐Tosylhydrazones

Synthesis of Ketones by C−H Functionalization of Aldehydes with Boronic Acids under Transition‐Metal‐Free Conditions

Synthesis of Ketones by C−H Functionalization of Aldehydes with Boronic Acids under Transition‐Metal‐Free Conditions

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Synthesis of Pyrrolidines by a Csp³‐Csp³/Csp³‐N Transition‐Metal‐Free Domino Reaction of Boronic Acids with γ‐Azido‐N‐Tosylhydrazones

Synthesis of Pyrrolidines by a Csp³‐Csp³/Csp³‐N Transition‐Metal‐Free Domino Reaction of Boronic Acids with γ‐Azido‐N‐Tosylhydrazones