tBuLi‐Mediated One‐Pot Direct Highly Selective Cross‐Coupling of Two Distinct Aryl Bromides

A Pd‐catalyzed direct cross‐coupling of two distinct aryl bromides mediated by tBuLi is described. The use of [Pd‐PEPPSI‐IPr] or [Pd‐PEPPSI‐IPent] as catalyst allows for the efficient one‐pot synthesis of unsymmetrical biaryls at room temperature. The key for this selective cross‐coupling is the use of an ortho‐substituted bromide that undergoes lithium–halogen exchange preferentially.     

Cross‐Coupling/Cyclization Reactions of Two Different Allenic Moieties

The allene moiety represents an excellent building block for allene cross‐coupling cyclization reactions, affording heterocyclic skeletons in a single step. This strategy is of particular interest when two different allene derivatives are involved in a series of metal‐catalyzed cross‐coupling heterocyclization processes. This Concept article is focused on the Pd‐catalyzed union of two different allenic moieties, with cyclization of at least one of them by intramolecular cyclometalation. These new, versatile, and highly effective transformations are complex multistep processes leading to potential privileged structures that could find wide applications in related medicinal chemistry.     

Cobalt‐Catalyzed Negishi Cross‐Coupling Reactions of (Hetero)Arylzinc Reagents with Primary and Secondary Alkyl Bromides and Iodides

We report a cobalt‐catalyzed cross‐coupling of di(hetero)arylzinc reagents with primary and secondary alkyl iodides or bromides using THF‐soluble CoCl₂?2 LiCl and TMEDA as a ligand, which leads to the corresponding alkylated products in up to 88 % yield. A range of functional groups (e.g. COOR, CN, CF₃, F) are tolerated in these substitution reactions. Remarkably, we do not observe rearrangement of secondary alkyl iodides to unbranched products. Additionally, the use of cyclic TBS‐protected iodohydrins leads to trans‐2‐arylcyclohexanol derivatives in excellent diastereoselectivities (up to d.r.=99:1).     

Gold‐Catalyzed Homogeneous Oxidative Cross‐Coupling Reactions

Oxidizing gold? A gold(I)/gold(III) catalytic cycle is essential for the first oxidative cross‐coupling reaction in gold catalysis. By using Selectfluor for gold(I) oxidation, this chemistry reveals the synthetic potential of incorporating gold(I)/gold(III) catalytic cycles into contemporary gold chemistry and promises a new area of gold research by merging powerful gold catalysis and oxidative metal‐catalyzed cross‐coupling reactions.

     

Double Heck Cross‐Coupling Reactions of Dibrominated Pyridines

Double Heck cross‐coupling reactions of 2,3‐ and 3,5‐dibromopyridine with various alkenes afforded the corresponding novel di(alkenyl)pyridines. The Heck reaction of 2,5‐dibromopyridine unexpectedly afforded 5,5′‐di(alkenyl)‐2,2′‐bipyridines by palladium‐catalyzed dimerization to give 5,5′‐dibromo‐2,2′‐bipyridine and subsequent twofold Heck reaction.     

Palladium‐Catalysed Direct Cross‐Coupling of Organolithium Reagents with Aryl and Vinyl Triflates

A palladium‐catalysed cross‐coupling of organolithium reagents with aryl and vinyl triflates is presented. The reaction proceeds at 50 or 70 °C with short reaction times, and the corresponding products are obtained with moderate to high yields, with a variety of alkyl and (hetero)aryl lithium reagents.     

LiCl‐Mediated Preparation of Functionalized Benzylic Indium(III) Halides and Highly Chemoselective Palladium‐Catalyzed Cross‐Coupling in a Protic Cosolvent

Sensitive functional groups such as COR, CHO, or CH₂OH can be present in benzylic indium reagents prepared by the direct insertion of indium in the presence of LiCl. These reagents undergo palladium‐catalyzed cross‐coupling reactions in the presence of a protic cosolvent after activation with iPrMgCl⋅LiCl (see scheme). Remarkable chemoselectivities are achieved by using various electrophiles containing NH or OH groups.

     

Organoaluminum‐Mediated Direct Cross‐Coupling Reactions

We present a direct cross‐coupling reaction between arylaluminum compounds (ArAlMe₂?LiCl) and organic halides RX (R=aryl, alkenyl, alkynyl; X=I, Br, and Cl) without any external catalyst. The reaction takes place smoothly, simply upon heating, thereby enabling the efficient and chemo‐/stereoselective formation of biaryl, alkene, and alkyne coupling products with broad functional group compatibility.     

Pd‐PEPPSI‐IPent: An Active,Sterically Demanding Cross‐Coupling Catalyst and Its Application in the Synthesis of Tetra‐Ortho‐Substituted Biaryls

Incredible Bulk : A series of N‐heterocyclic carbene catalysts (see picture) were prepared and evaluated in the Suzuki–Miyaura reaction. A variety of sterically encumbered tetra‐ortho‐substituted biaryl products were formed from unreactive aryl chlorides using the isopentyl‐substituted catalyst at temperatures ranging from 65 °C to room temperature. The cyclopentyl‐substituted catalyst was virtually inactive, demonstrating that “flexible bulk” is essential to promote these transformations.

     

Nickel‐Mediated Inter‐ and Intramolecular Reductive Cross‐Coupling of Unactivated Alkyl Bromides and Aryl Iodides at Room Temperature

A nickel‐mediated intermolecular reductive cross‐coupling reaction of unactivated alkyl bromides and aryl iodides at room temperature has been developed and successfully extended to less explored intramolecular versions and tandem cyclization‐intermolecular cross‐coupling. Highly stereoselective (or stereospecific) synthesis of linear‐fused perhydrofuro[2,3‐b]furan (pyran) and spiroketal skeletons allows rapid access to these useful building blocks, which would be potentially valuable in the synthesis of relevant natural products. A rational explanation for the formation of contiguous stereogenic centers is given.     

Six‐ and Eightfold Palladium‐Catalyzed Cross‐Coupling Reactions of Hexa‐ and Octabromoarenes

Palladium‐catalyzed sixfold coupling of hexabromobenzene ( 20 ) with a variety of alkenylboronates and alkenylstannanes provided hexaalkenylbenzenes 1 in up to 73 % and 16 to 41 % yields, respectively. In some cases pentaalkenylbenzenes 21 were isolated as the main products (up to 75 %). Some functionally substituted hexaalkenylbenzene derivatives containing oxygen or sulfur atoms in each of their six arms have also been prepared (16 to 24 % yield). The sixfold coupling of the less sterically encumbered 2,3,6,7,10,11‐hexabromotriphenylene ( 24 ) gave the desired hexakis(3,3‐dimethyl‐1‐butenyl)triphenylene ( 25 ) in 93 % yield. The first successful cross‐coupling reaction of octabromonaphthalene ( 26 ) gave octakis‐(3,3‐dimethyl‐1‐butenyl)naphthalene ( 27 ) in 21 % yield. Crystal structure analyses disclose that, depending on the nature of the substituents, the six arms are positioned either all on the same side of the central benzene ring as in 1 a and 1 i , making them nicely cup‐shaped molecules, or alternatingly above and below the central plane as in 1 h and 23 . In 27 , the four arms at C‐1,4,6,7 are down, while the others are up, or vice versa. Upon catalytic hydrogenation, 1 a yielded 89 % of hexakis(tert‐butylethyl)benzene ( 23 ). Some efficient accesses to alkynes with sterically demanding substituents are also described. Elimination of phosphoric acid from the enol phosphate derived from the corresponding methyl ketones gave 1‐ethynyladamantane ( 3 b , 62 % yield), 1‐ethynyl‐1‐methylcyclohexane ( 3 c , 85 %) and 3,3‐dimethylpentyne ( 3 e , 65 %). 1‐(Trimethylsilyl)ethynylcyclopropane ( 7 ) was used to prepare 1‐ethynyl‐1‐methylcyclopropane ( 3 d ) (two steps, 64 % overall yield). The functionally substituted alkynes 3 f – h were synthesized in multistep sequences starting from the propargyl chloride 11 , which was prepared in high yields from the dimethylpropargyl alcohol 10 (94 %). The alkenylstannanes 19 were prepared by hydrostannation of the corresponding alkynes in moderate to high yields (42–97 %), and the alkenylboronates 2 and 4 by hydroboration with catecholborane (27–96 % yield) or pinacolborane (26–69 % yield).