C-H結合の活性化によるヘテロサイクルのRh (I) -触媒化されたアリレーション: 機械的洞察を通して拡張された範囲
Jared C Lewis1, Ashley M Berman, Robert G Bergman
1Department of Chemistry, University of California and Division of Chemical Sciences, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Journal of the American Chemical Society
|February 7, 2008
まとめ
新しいRh触媒による直接アリレーション法により,アゾールとアリルブロミドの効率的な結合が可能になりました. この機能群耐性プロセスは,新しいリガンドを使用し,反応と製品分離を簡素化します.
科学分野:
- 有機化学 オーガニック・ケミストリー
- カタリシス カタリシス カタリシス
- 薬用化学 薬用化学について
背景:
- ヘテロサイクルの直接のアリレーションは,薬学的に重要な化合物の合成に不可欠です.
- パラジウム (Pd) または銅 (Cu) 触媒を用いた既存の方法は,しばしば機能群の許容性が欠如し,厳しい条件を必要とする.
- アゾールは重要な製薬体であり,その電子特性により,直接アリレーションにユニークな課題を提示します.
研究 の 目的:
- アゾールとアリルブロミドの直接アリレーションのための新しい,実用的で,機能的なグループ耐性メソッドを開発する.
- この変換のための高度に活発で熱的に安定した触媒システムを特定する.
- 処理と浄化を簡素化し,マイクロ波合成と互換性のある反応条件を確立する.
主な方法:
- アリルブロミドを用いたロジウム (Rh) 触媒による直接アリレーション.
- 簡単に作製できる低分子量リガンドであるZ-1-tert-butyl-2,3,6,7-tetrahydrophosphepineを使用し,Rhに二重型P-olefinで調整されます.
- 対応するフォスフォニウムのテトラフルオロボラート塩を用いて,空気に安定した組み立てを行い,THFまたはダイオキサンで反応を行う.
主要な成果:
- 薬学的に重要な様々なアゾールをアリルブロミドで直接アリル化することに成功した.
- 機能群の許容性が実証されており,PdまたはCu触媒と互換性のない結合パートナーに対応しています.
- マイクロ波加熱を使用して2時間以内に優れた製品収量を達成しました.
- 伝統的な高沸騰度アミド溶媒と比較して,単純化された反応セットアップと製品分離.
結論:
- 開発されたRh触媒方式は,アゾールの直接アリレーションのための実用的で効率的な経路を提供します.
- 新種のフォスフィンリガンドと反応条件により,頑丈で汎用性の高い触媒システムが作られます.
- このアプローチは,医薬品化学で広く適用可能な複雑なアゾール誘導体の合成を容易にする.
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02:24Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
Introduction
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
Introduction
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
01:25Radical Anti-Markovnikov Addition to Alkenes: Overview
The addition of hydrogen bromide to alkenes in the presence of hydroperoxides or peroxides proceeds via an anti-Markovnikov pathway and yields alkyl bromides.
02:38Electrophilic Addition to Alkynes: Halogenation
Introduction
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.