Intramolecular Diels−Alder Reactions of Optically Active Allenic Ketones:  Chirality Transfer in the Preparation of Substituted Oxa-Bridged Octalones

Abstract

The intramolecular Diels-Alder reaction of allenic ketones containing a furyl unit (IMDAF) to generate oxatricyclic systems in good yields is described. The alkene dienophiles 1ab give poor yields of the cycloadducts 2ab, presumably due to the facile retro Diels-Alder reaction. However, the analogous allenic dienophile 7 afforded the desired cycloadduct 8 in 91% yield on treatment with dimethylaluminum chloride. When the allene bears an alkyl substituent on the terminal carbon, complete diastereoselectivity is seen in the IMDAF, e.g. cyclization of 14 gave only the cycloadduct 15 in 80% yield presumably due to greater steric hindrance in the transition state II as compared to that in I. Finally we report complete chirality transfer of the stereochemistry of an allene to the carbon framework of the oxatricyclic system. Thus, the optically active allenic ketone 20 afforded only the desired cycloadduct 21 with the correct absolute stereochemistry needed for the synthesis of the arisugacin class of natural products.

Synergistic Gold and Copper Dual Catalysis for Intramolecular Glaser–Hay Coupling: Rapid Total Synthesis of Ivorenolide B

“…Oxidation of allylic alcohol with Dess–Martin‐periodinane (DMP) furnished the α,β‐unsaturated aldehyde, which was subjected to zinc‐ProPhenol‐catalyzed alkyne addition to provide the propargyl alcohol 20 in 94 % enantiomeric excess and with 91 % yield , . At this juncture, in anticipation for a better result, the substrate 20 (for results, see Table ) was prepared by BINOL‐mediated alkyne addition, oxidation followed by Noyori asymmetric hydrogenation and enzymatic kinetic resolution…”

The Origin of the Halogen Effect on Reactivity and Reversibility of Diels–Alder Cycloadditions Involving Furan

“…The possibility that simple halogen substitution might convert previously failed furan cycloadditions into successes caused us to explore the origin and generality of this halogen effect. A number of apparently reasonable cycloadditions have been found to be unsuccessful, usually due to substrate inertness8 or the tendency for products to undergo retrocycloadditions 9–11. A celebrated example is the unattainable direct synthesis of cantharidin ( 6 ) 12.…”

“…A celebrated example is the unattainable direct synthesis of cantharidin ( 6 ) 12. Figure 1 illustrates products of failed cycloadditions ( 8 and 9 ) as well as low‐yielding cycloadditions ( 10 and 11 ) 11. 13 Cram's polycycle ( 7 ) exemplifies the sensitivity of these reactions to retrocycloadditions at increased temperatures 14.…”

Diastereoselective Synthesis of Bridged Polycyclic Alkaloids via Tandem Acylation/Intramolecular Diels–Alder Reaction

“…The activated dienophile and diene-containing intermediate B are expected to undergo [4 + 2] intramolecular Diels–Alder cycloaddition to provide a novel bridged multicyclic architecture, C . Moreover, it was contemplated that the successive chirality transfer from an optically active amino acid can lead to a stereoselective Diels–Alder cycloaddition product . This approach would allow for rapid and efficient construction of structurally and stereochemically complex molecules with multiple rings and chiral centers under mild conditions in a tandem fashion from readily available chiral amino acids, which is extremely valuable in organic synthesis.…”