Intra- and intermolecular reactions of indoles with alkynes catalyzed by gold

Indoles react intramolecularly with alkynes in the presence of gold catalysts to give from six- to eight-membered-ring annulated compounds. The cationic Au(I) complex [Au(P{C(6)H(4)(o-Ph)}(tBu)(2))(NCMe)]SbF(6) is the best catalyst for the formation of six- and seven-membered rings by 6-endo-dig, 6-exo-dig, and 7-exo-dig cyclizations. Indoloazocines are selectively obtained with AuCl(3) as catalyst in a rare 8-endo-dig process. In this process allenes or tetracyclic annulated derivatives are also formed as a result of an initial fragmentation reaction. The intermolecular reaction of indoles with alkynes proceeds to form 3-alkenylated intermediates that react with a second equivalent of indole to give bisindolyl derivatives. Indoles that are substituted at the 3-position react intermolecularly with alkynes to give 2-alkenylated intermediates that can be trapped intramolecularly with the appropriate nucleophiles.     

Studies on Pd(0)-catalyzed cyclization of N-3,4-alkadienyl toluenesulfonamides with organic halides: selective synthesis of 2,3-dihydropyrroles, 1,2,3,6-tetrahydropyrridines, and azetidines

The palladium-catalyzed coupling-cyclization of beta-amino allenes with organic halides ranging from aryl halide to 1-alkenyl halide was studied. 2,3-Dihydro-1H-pyrroles were obtained by reaction of 3-substituted-5-unsubstituted-3,4-allenyl amides under conditions A, while the reaction of 5-substituted-3,4-allenyl amides afforded 1,2,5,6-tetrahydropyridines and/or azetidines with high de under conditions B or C. The skeleton and relative configuration of the six-membered products were established by the X-ray diffraction studies of 10 ka. Allenyl amide 4 q reacted with 1,4-diiodobenzene 6 r to afford double cyclization product 15. The structure of its major stereoisomer was also determined by the X-ray diffraction study.     

Intramolecular Alkynylogous Mukaiyama Aldol Reaction Starting from Bicyclic Alkanones Tethered to Alkynyl Esters: Formal Total Synthesis of (±)‐Hamigeran B

Selecting the ring : tert‐Butyldimethylsilyltriflate (TBSOTf)/NEt₃ treatment of alkynyl esters tethered to bicycloalkanones leads to the formation of tricyclic allenoates with total diasteroselectivity at the ring junction. An intramolecular alkynylogous Mukaiyama aldol reaction promoted by a TBSOTf/NEt₃ dual activation is involved. This novel methodology was illustrated by a formal total synthesis of (±)‐hamigeran B.

     

Regioselectivity Control in the Metal‐Catalyzed Functionalization of γ‐Allenols,Part 2: Theoretical Study

Calculating cyclization : Theoretical work directed towards the elucidation of the mechanisms of the gold‐, palladium‐, and lanthanum‐catalyzed oxycyclizations (5‐exo versus 6‐endo versus 7‐endo) of γ‐allenols has been pursued in close relationship with the experimental study (Part 1, accompanying paper) and has corroborated the bench results to provide a complete study of the reactivity of γ‐allenols under different metal‐catalyzed conditions.

     

Palladium‐Catalyzed Intramolecular Hydroamination of Allenes Coupled to Aerobic Alcohol Oxidation

Taking the air! A Pd^II‐catalyzed intramolecular hydroamination of allenes coupled to alcohol oxidation has been developed. This reaction is performed by using a nitrogen‐based ligand under aerobic conditions, under which the molecular oxygen is used as the terminal oxidant for the reoxidation of Pd⁰ species to complete the catalytic cycle.

     

Chemo‐ and Regioselective Palladium‐Catalyzed Oxycyclization Reactions of Allendiols: Preparation of Five‐, Six‐, and Eight‐Membered Cycles

Positive discrimination : Chemo‐ and regioselective palladium‐catalyzed cycloetherification of allendiols, namely β,γ‐ and γ,δ‐allendiols, may occur by judicious choice of palladium‐catalyzed conditions owing to their potential ability to discriminate between both nucleophilic sites (see scheme).

     

1‐Phenyl‐1,2‐cyclohexadiene: Astoundingly High Enantioselectivities on Generation in a Doering–Moore–Skattebøl Reaction and Interception by Activated Olefins

The resolution of (1α,5α,6α)‐6‐bromo‐6‐fluoro‐1‐phenylbicyclo[3.1.0]hexane (rac‐ 5) provided the enantiomerically pure precursors (?)‐ 5 and (+)‐ 5 of 1‐phenyl‐1,2‐cyclohexadiene. On treatment of (?)‐ 5 with methyllithium in the presence of 2,5‐dimethylfuran, the pure (?)‐enantiomer of the [4+2] cycloadduct of 2,5‐dimethylfuran onto 1‐phenyl‐1,2‐cyclohexadiene was obtained exclusively. From this result, it is concluded that pure (M)‐1‐phenyl‐1,2‐cyclohexadiene ((M)‐ 7 ) emerged from (?)‐ 5 and was enantiospecifically intercepted to give the product. In the case of indene as trap for (M)‐ 7 , the (?)‐ and the (+)‐enantiomer of the [2+2] cycloadduct were formed in the ratio of 95:5. Highly surprising, remarkable enantioselectivities were also observed, when (M)‐ 7 was trapped with styrene to furnish two diastereomeric [2+2] cycloadducts. Hence, the achiral conformation of the diradical conceivable as intermediate cannot play a decisive part. The enantioselective generation of (M)‐ and (P)‐ 7 by the β‐elimination route was tested as well. Accordingly, 1‐bromo‐2‐phenylcyclohexene was exposed to the potassium salt of (?)‐menthol in the presence of 2,5‐dimethylfuran, and the enantiomeric [4+2] cycloadducts of the latter onto (M)‐ and (P)‐ 7 were produced in the ratio of 55:45.     

A Synthesis of an Ionomycin Calcium Complex

Caught in the middle : The ionomycin calcium complex (see structure; O red, Ca green) was the target of an approach featuring the efficient asymmetric synthesis of an allene by a copper(I)‐mediated anti‐selective S_N2′ reaction, a highly stereoselective gold(III)‐catalyzed cycloisomerization of an α‐hydroxyallene, and a Rh‐catalyzed rearrangement of an α‐diazo‐β‐hydroxyketone.

     

Synthesis of 3,4‐Dihalogenated Furan‐2‐(5 H)‐ones by Electrophilic Cyclization of 4‐Hydroxy‐2‐alkynoates

Functionalized 3,4‐dihalogenated furan‐2(5 H)‐ones can be readily prepared in moderate to good yields by treating 4‐hydroxy‐4‐arylbut‐2‐ynoate derivatives with ICl, IBr, and I₂. Both halogen atoms of the electrophile are incorporated in the product. The resulting halides can further afford polycyclic aromatic compounds using known palladium‐catalyzed coupling reactions.