An official website of the United States government
Abstract Rh(I)‐catalyzed C8‐selective C−H alkenylation and arylation of 1,2,3,4‐tetrahydroquinolines with alkenyl and aryl carboxylic acids under microwave assistance have been realized. Using [Rh(CO)2(acac)] as the catalyst and Piv2O as the acid activator, 1,2,3,4‐tetrahydroquinolines undergo C8‐selective decarbonylative C−H alkenylation with a wide range of alkenyl and aryl carboxylic acids, affording the C8‐alkenylated or arylated 1,2,3,4‐tetrahydroquinolines. This method enables the synthesis of C8‐alkenylated 1,2,3,4‐tetrahydroquinolines that would otherwise be difficult to access by means of conventional C−H alkenylation protocols. Moreover, this catalytic system also works well in C8‐selective decarbonylative C−H arylation of 1,2,3,4‐tetrahydroquinolines with aryl carboxylic acids. The catalytic activity strongly depends on the choice of theN‐directing group, with the readily installable and removableN‐(2‐pyrimidyl) group being optimal. The catalytic pathway is elucidated by mechanistic experiments.
more »
« less
Nitrene C−H Bond Insertion Approach to Carbazolones and Indolones, and a Reactivity Departure for 7‐Membered Analogues**
Abstract A modular platform for facile access to 1,2,3,9‐tetrahydro‐4H‐carbazol‐4‐ones (H4‐carbazolones) and 3,4‐dihydrocyclopenta[b]indol‐1(2H)‐ones (H2‐indolones) is described. The requisite 6‐ and 5‐membered 2‐arylcycloalkane‐1,3‐dione precursors were readily obtained through a Cu‐catalyzed arylation of 1,3‐cyclohexanediones or by a ring expansion of aryl succinoin derivatives. Enolization of one carbonyl group in the diones, conversion to a leaving group, and subsequent azidation gave 2‐aryl‐3‐azidocycloalk‐2‐en‐1‐ones. This two‐step, one‐pot azidation is highly regioselective with unsymmetrically substituted 2‐arylcyclohexane‐1,3‐diones. The regioselectivity, which is important for access to single isomers of 3,3‐disubstituted carbazolones, was analyzed mechanistically and computationally. Finally, a Rh‐catalyzed nitrene/nitrenoid insertion into theorthoC−H bond of the aryl moiety gave the H4‐carbazolones and H2‐indolones. One carbazolone was elaborated to an intermediate reported in the total synthesis ofN‐decarbomethoxychanofruticosinate, (−)‐aspidospermidine, (+)‐kopsihainanine A. With 2‐phenylcycloheptane‐1,3‐dione, prepared from cyclohexanone and benzaldehyde, the azidation reaction was readily accomplished. However, the Rh‐catalyzed reaction unexpectedly led to a labile but characterizable azirine rather than the indole derivative. Computations were performed to understand the differences in reactivities of the 5‐ and 6‐membered 2‐aryl‐3‐azidocycloalk‐2‐en‐1‐ones in comparison to the 7‐membered analogue, and to support the structural assignment of the azirine.
more »
« less
- Award ID(s):
- 1953574
- PAR ID:
- 10473094
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- Volume:
- 29
- Issue:
- 72
- ISSN:
- 0947-6539
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Computational studies revealed that dirhodium tetrakis(1,2,2‐triarylcyclopropanecarboxylate) (Rh2(TPCP)4) catalysts adopt distinctive high symmetry orientations, which are dependent on the nature of the aryl substitution pattern. The parent catalyst, Rh2(TPCP)4, and those with ap‐substituent at the C1 aryl, such as Rh2(p‐BrTPCP)4and Rh2(p‐PhTPCP)4, adopt aC2‐symmetric structure. Rh2(3,5‐di(p‐tBuC6H4)TPCP)4, 3,5‐disubstituted at the C1 aryl, adopts aD2‐symmetric structure, whereas catalysts with ano‐substituent at the C1 aryl, such as Rh2(o‐Cl‐5‐BrTPCP)4,adopt aC4‐symmetric structure.more » « less
-
Catalytic site-selective hydroallylation of vinyl arenes and 1,3-dienes is reported. Transformations are promoted by a readily accessible bidentate carbodicarbene-rhodium complex and involve commercially available allyltrifluoroborates and an alco-hol. The reaction is applicable to vinyl arenes, and aryl or alkyl-substituted 1,3-dienes (30 examples). Allyl addition products are generated in 40–78% yield and in up to >98:2 site-selectivity. Reaction outcomes are consistent with the intermedi-acy of a Rh(III)-hydride generated by protonation of Rh(I) by an acid. A number of key mechanistic details of the reaction are presented: (1) Deuterium scrambling into the product and starting alkene indicates reversible Rh(III)–H migratory insertion. (2) A large primary kinetic isotope effect is observed. (3) With substituted allyltrifluoroborates (e.g., crotyl-BF3K) mixtures of site isomers are generated as a result of transmetalation followed by Rh-(allyl) complex equilibration; consequently, disproving outer-sphere addition of the allyl nucleophile to Rh(III)-(η3-allyl). (4) The stereochemical analysis of a cyclohexadiene allyl addition product supports a syn Rh(III)–hydride addition. (5) A Hammett plot shows a negative slope suggesting reductive elimination as the rate-determining step. Finally, utility is highlighted by a iodocyclization and cross metathesis.more » « less
-
Abstract A Rh(II)/Au(I) catalyzed carbene cascade approach for the stereoselective synthesis of diverse spirocarbocycles is described. The cascade reaction involves a rhodium carbene initiatedsp2C−H functionalization followed by a gold catalyzed Conia‐ene cyclization. The cascade reaction accommodates a variety of aryl substituents as well as ring sizes and proceeds with high diastereoselectivity providing access to diverse spirocarbocycles. magnified imagemore » « less
-
Abstract Cp*Rh(III)‐catalyzed chelation‐assisted direct C−H bond functionalization of 1‐(2‐pyridyl)‐2‐pyridones with internal alkynes that can be controlled to give three different products in good yields has been realized. Depending on the reaction conditions, solvents and additives, the reaction pathway can be switched between alkenylation, alkenylation/directing group migration and rollover annulation. These reaction manifolds allow divergent access to a variety of valuable C6‐alkenylated 1‐(2‐pyridyl)‐2‐pyridones, (Z)‐6‐(1,2‐diaryl‐2‐(pyridin‐2‐yl)vinyl)pyridin‐2(1H)‐ones and 10H‐pyrido[1,2‐a][1,8]naphthyridin‐10‐ones from the same starting materials. These protocols exhibit excellent regio‐ and stereoselectivity, broad substrate scope, and good tolerance of functional groups. A combination of experimental and computational approaches have been employed to uncover the key mechanistic features of these reactions.more » « less
