Construction of the Benzindenoazepine Skeleton via Cyclopentannulation of Fischer Aminocarbene Complexes:  Total Synthesis of Bulgaramine

Abstract

A total synthesis of bulgaramine has been accomplished with a longest linear sequence of eight steps and an overall yield of 23% from commercially available 3,4-dimethoxyphenethyl alcohol. An intramolecular cyclopentannulation reaction of a Fischer aminocarbene complex provided the key step and occurred under significantly milder conditions and in higher yields than those of other reported examples of this reaction type. The reaction solvent was a critical factor in the cyclopentannulation reaction, with measurable amounts of the desired product observed only when THF was utilized. The product yield could be further enhanced by the addition of two-electron donor ligands, demonstrating the first example of this effect on the thermal reaction of aminocarbene complexes with alkynes.

Disassembling Metal Nanocrystallites into Sub‐nanometric Clusters and Low‐faceted Nanoparticles for Multisite Catalytic Reactions

“…DMF was used as a solvent instead of N ‐methyl‐2‐pyrrolidone (NMP) for easier removal in the aqueous phase during the work‐up, and a nitrogen atmosphere was used to minimize the homocoupling of the alkyne. In any case, the classical PdCl 2 (PPh 3 ) 2 /CuI catalytic system for the Sonogashira reaction is expected to work very well for this reaction,– thus the advantages of using Au here lies in the absence of ligands, the potential recovery of the single metal at the end of the reaction, and the low amount of residual metal in the final product.…”

Transition metals in organic synthesis: Highlights for the year 2005

“…An interesting annulation of an amino carbene complex was used in a synthesis of bulgaramine (Eq. (397)) [334].…”

“…Examples of synthetic targets include, 10-hydroxyasimicin [322], cylindramine [323], murisolins [324], norzoanthamine [325], salicylihalamide core [326], (+)-laudanosine and (−)-xylopine [327], 5,5-difluoroleukotrienes B 3 [328], dehydrocoelenterazine analogs [204], (−)-epiindolizidine 167B and 5E,9Z-indolizidine 223AB [329], (+)-allocyathine B 2 [128], amphidinolides T1 and T4 [330], (4E,6Z,10Z)-4,6,10-hexadecatrien-1-ol [331], diacetylenic spiroacetal enol ethers [332], epoxyquinoid compounds [53], heliophenanthrone [333], bulgaramine [334], (−)-siphonodiol [335], the ergoline skeleton [336], (−)-isoprelaurefucin [337], elipticine [338], pyranicin [339], peroxyacarnoates A and D [66], allocolchicinoid [340], (−)-217 A [341], DE ring system of upenamide [342], A2E [73], ␣-glycosylindole [343], mycolactones A and B [296], (+)-obtusenyne [344], tetradec-6-en-1,3-diyne-13-one [345], virol C and 1-dehydroxyvirol A [346], terreinol [347], (+)-trifluoromethyl monomorine [348], 2E,4E,6E,11Z-octadecatetraenoic acid [239], 7(S),17(S)-resolvin D5 [349], erogorgiaene [350], solamine analogs [351], longimicin C [352], furanopyrimidine nucleoside analogs [353] and polyacetylenic acids …”

“…(282)) [57]. A related cyclization was used in a synthesis of heliophenanthrone [334]. Gold catalyzed the cycloisomerization of 1-halo-4-oxo-1,2-dienes to give halogenated furans.…”

Product Class 6: Oxonium Salts

“…There are many procedures utilizing metals in group 6, including chromium (e.g., synthesis of carbene 10 from O/Br acetal 9) (Scheme 8), [81][82][83][84] tungsten, [85,86] and molybdenum, [87,88] as well as ruthenium, [89] manganese, [90] and iron. [90] The anionic nucleophile can be varied to accommodate different functionalities, such as alkyl, [91,92] aryl, [82,93] amino, [94] or silyl groups. [95] Although not as common as the Fischer carbene preparation, there are examples of other metal-based O-alkylations using tungsten, [96] iron, [97] and rhenium.…”