Allenyl indoles

The first carbon addition to allenes catalyzed by gold was described by Hashmi and was the addition of furans to allenones, a reaction that is discussed as a conjugate addition to carbonyls. Then the annulation of 2-allenyl indoles was described (equation 111)and an enantioselective version was later developed for terminal allenes. Then Nelson described the cyclization of an N-substituted pyrrol in the synthesis of (—)-Rhazinilam (equation 112). In that case, gold notably improved the yields and selectivities obtained with Pd(II) or Ag(l), and gave complete retention of the chiral information of the allene. The most recent report is on the hydroarylations of allenes with gold-covered substituted benzenes as substrates. ""... 

A catalytic 1 1 mixture of Au[P(/-Bu)2(o-biphenyl)]Cl and AgOTf promoted the room-temperature intramolecular exo hydroarylation of 2-allenyl indoles to give tetrahydrocarbazoles (Scheme 18.16) [15], For example, treatment of 2-(4,5-hexadienyl)indole with the Au-catalyst mixture gave tetrahydrocarbazole in greater than 99% yield. 

This intramolecular hydroarylation was applied to the synthesis of a chiral cyclic product. Treatment of 2-allenyl indole with a catalytic 1 2 mixture of [(S)-P-P]Au2Cl2 [(S)-P-P = (S)-3,5-fBu-4-MeOMeOBIPHEP] and AgBp4 in toluene at -10 °C for 17 h gave tetrahydrocarbazole in 88% yield with 92% ee (Scheme 18.17) [16],... 

When propargylamine 183 was subjected to a homologative allenylation (Crabbe reaction) at 100 °C, the resulting allene underwent a spontaneous Diels-Alder reaction to give the adduct 184. This intramolecular cycloaddition-oxidation sequence provided a simple route to indole alkaloids such as hippadine and ds-trikentrin B [148]. 

Imidates, rearrangement of, 14, 1 Imines, additions of allyl, allenyl, propargyl stannanes, 64, 1 additions of cyanide, 70, 1 as dienophiles, 65, 2 synthesis, 70, 1 Iminium ions, 39, 2 65, 2 Imino Diels-Alder reactions, 65, 2 Indoles, by Nenitzescu reaction, 20, 3 by reaction with TosMIC, 57, 3 Ionic hydrogenation, 71, 1 Isocyanides, in the Passerini reaction, 65, 1... 

Blechert has developed an interesting synthesis of 2-substituted indoles which involves the conjugate addition of V-phenylhydroxylamine salts (or V-phenylnitrones) to electron-deficient allenes, followed by carbanion-accelerated hetero-Cc rearrangement of the Michael adduct. For exanple, addition of the hydroxylamine salt (46) to the allenyl sulfone (47) produces the anion (48), which undergoes rapid 3.3-sigmatropic rearrangement to afford the -keto sulfone (49). Cyclization to the indole proceeds smoothly upon exposure to formic acid (Scheme 3). 

Echavarren and co-workers reported the Au(I)-catalysed introduction of oxygenated prenyl groups at C3 by treating indole with isoprenoid feri-propargyl esters [123], obtaining double bond regioisomers in part. Propargylation of indole derivatives has also led to the formation of bisindoles [53] and allenylated products and quinoline derivatives [56],... 

Intramolecular enolate addition to an -fluoroacrylate was a key step in the synthesis of a heteroyohimbine indole alkaloid containing a 2,3-dihydrofuran moiety <01SL1125>. An endo ring closure at the s/j-hybridized carbon center of an allenyl unit to form a 2,3-dihydrofuran as shown below was observed when the allenyl sulfoxide containing a primary 6-hydroxy group was allowed to react with potassium rert-butoxide <01OL3385>. 

Cross-coupling of the propargyl carbonate 58 with the indolylborate 59 gave the allenyl ketone 60, which, without isolation, underwent 1,4-addition to the allenyl ketone in 60 to afford the cyclopenta[fe]indole derivative 61 [13],... 

Although the products are not natural, the synthesis of indole derivatives shown in Scheme 37 is noteworthyJ " f Interestingly, a-allenylation and /3-propargylation with concomitant a-ethylation have been observed. The ethyl gronp is derived from EtaB used as a boron reagent. 

More recently, Saito and Hanzawa demonstrated that a variety of fused, tri-, tetra-and penta-substituted indoles 190 could be efficiently accessed via the Rh(I)-catalyzed cydoisomerization of N-propargyl anilines 188 (Scheme 9.68) [225, 226]. This transformation presumably involves the initial Rh(I)-catalyzed amino-Claisen rearrangement of 188 to produce a putative reactive allenyl aniline intermediate 189, which is smoothly converted into the indole core, as exemplified by the cycloisomerization of an independently prepared allene 191 (Scheme 9.69). On the other hand, the latter transformation of allenes can be achieved under thermal reaction conditions, albeit with a diminished effidency. 

Ma and coworkers reported the gold-catalysed cyclisation of l-(indol-2-yl)-3-allg n-l-ol derivatives to afford carbazoles at room temperature. The transformation was promoted by 5 mol% of gold(in) chloride and the corresponding carbazoles were isolated in moderate to veiy good yields (Scheme 16.63). In an earlier report the authors also showed two examples of the gold-catalysed formation of carbazoles using l-(indol-2-yl)-2-allenyl-l-ols as precursors. 

Scheme 16.63 Gold-promoted synthesis of carbazoles from l-(indol-2-yl)-3-alkyn-l-ols or l-(indol-2-yl)-2-allenyl-l-ols.

Also nitrenes, generated from the allenyl azides 99, undergo the [2+1] cycloaddition reaction to give the annelated indole derivatives 100. ... 

Heating of the 2-(allenyl)phenyl azides 79 at 110 °C gave a mixture of the cyclopent-annelated indoles 80 and 81 °. ... 

Indole derivatives tethered by alkenyl or allenyl groups undergo efficient intramolecular hydroarylation. Treatment of 2-(4-pentenyl)indoles with a catalytic platinum/chiral phosphine complex induced intramolecular hydroarylation to give tetrahydrocarbazole in 93% yield with 90% ee (Scheme 18.14) [13], The similar intramolecular asymmetric hydroarylation was applied to indoles having internal olefins by use of a highly strained planar chiral platinacycle (Scheme 18.15) [14],... 

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