A Direct Organocatalytic Enantioselective Route to Functionalizedtrans‐Diels–Alder Products Having the Norcarane Scaffold

Abstract

An enantioselective methodology to construct trans-Diels-Alder scaffolds by organocatalysis with excellent selectivity,h igh yield and up to five contiguous stereocenters is presented. The reaction concept integrates the halogen effect and an ovel discovered pseudo-halogen effect to direct an endo-selective,s econdary-amine catalyzedD iels-Alder reaction allowing for the subsequent formation of trans-Diels-Alder cycloadducts featuring the norcarene scaffold. The methodology relies on the reaction between an in situ generated trienamine and an a-brominated or a-pseudo-halogenated enone to form af leeting cis-Diels-Alder intermediate.T he endo-transition state-enhanced by the (pseudo-)halogen effectsets the stereochemistry that allows for as ubsequent S N 2-like reaction at at ertiary center to obtain the trans-Diels-Alder scaffold. The mechanism was investigated and supported by experimental results as well as computational studies.

Synthesis of tetrasubstituted alkenyl nitriles via cyanocarbene addition of [1.1.1]propellane

“…28 Last but not least, the reduction of 3a with DIBAL-H provided enal 7 in 60% yield. 29 To shed further light on the underlying reaction mechanism of this transformation, the following control experiments were performed (Scheme 4). Initially, 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) was used as a radical inhibitor, however, the corresponding product could not be obtained.…”

A Direct Organocatalytic Enantioselective Route to Functionalizedtrans‐Diels–Alder Products Having the Norcarane Scaffold

“…Thea bsolute configuration of 4f was determined after derivatization into hydrazone 4g and subjected to X-ray crystallographic analysis (Scheme 4). [11] It demonstrates the expected trans-configuration between the fluorine and aldehyde group in the cis-O-hetero-Diels-Alder intermediate. Thelower diastereomeric ratio observed for the formation of 4f was investigated by control experiments and indicated reversibility facilitated by the catalyst (see Supporting Information).…”

“…Finally,t he aldehyde of 3a was transformed into hydrazone 4ein 69 %yield with an 11:1 E-/Z-ratio.The crystallinity of 4e enabled its absolute configuration to be obtained by Xray crystallographic analysis allowing structures 3a-3s to be assigned by analogy. [11] Then, we turned our attention to the nature of the S N 2-like substitution at the tertiary center. Three different mechanistic scenarios can be envisioned;t hrough the formation of ar adical intermediate,aconcerted S N 2-like transition state or as tepwise S N 1p athway with formation of ac arbocation intermediate (Scheme 3).…”

Strategies and Methods for the Catalytic Asymmetric Synthesis of Benzofuran/Benzopyran Fused Acetals: A Review

“…Later in 2021, the Jørgensen group reported an asymmetric O ‐hetero‐Diels–Alder reaction using 3‐substituent‐4 H ‐chromen‐4‐one 37 and 4‐hydroxy‐2‐enal 38 as substrates, affording products 39 in excellent yields and ees (Scheme 20, up to 85% yield, 99% ee and>20:1 dr) [40] …”