Palladium‐katalysierte asymmetrische Synthese von 2‐Alkinyl‐substituierten Sauerstoffheterocyclen

Abstract

Oxyacetylen: Zwei beispiellose Palladium‐katalysierte Cyclisierungen von cyclischen und acyclischen Carbonaten führen zum Aufbau von 2‐Alkinyltetrahydrofuranen und ‐tetrahydropyranen. Die Reaktionen verlaufen mit exzellenter Stereoselektivität für sowohl syn‐ als auch anti‐disubstituierte Tetrahydrofurane und Tetrahydropyrane und mit ausgezeichneter Regioselektivität. Zusätzlich wird über eine zweifache Cyclisierung zum Aufbau von Bis‐Tetrahydrofuranen berichtet, die mit vollständiger Stereoretention für alle Diastereomere erfolgt.

Ligand Bite Angle‐Dependent Palladium‐Catalyzed Cyclization of Propargylic Carbonates to 2‐Alkynyl Azacycles or Cyclic Dienamides

“…Investigations began with sulfonamide carbonate 4 a , which cyclized to pyrrolidine 5 a with excellent stereoselectivity under the conditions we had optimized for oxygen nucleophiles (Table 1, entry 1) 3. 6, 7 However, in contrast to our previous study, a significant amount of cyclic enamide 6 a was formed through competitive attack by the sulfonamide on the central carbon atom of the intermediate allenylpalladium species 3 (see mechanistic discussion below) 8.…”

“…Stereoselective heterocycle synthesis is of fundamental importance in pharmaceutical and natural product research 1. 2 We recently reported a palladium‐catalyzed asymmetric approach to 2‐alkynyl oxacycles from propargylic carbonates equipped with internal alcohol nucleophiles ( 1 → 2 , Nu=OH; Scheme ) 3. Key to this reaction is the high fidelity of stereochemical transfer from the carbonate to the oxacycle, and the high regioselectivity of attack by the oxygen nucleophile on the distal carbon atom of the intermediate allenylpalladium complex 3 , as opposed to the central carbon atom as is usually observed in such systems 4.…”

“…A dramatic switch in selectivity was observed between dppe ( 5 a / 6 a 19:81; Table 1, entry 6) and DPEphos ( 5 a / 6 a 89:11; entry 10),10 with a modest increase in stereoselectivity observed for the latter in 1,4‐dioxane (97 % ee ; entry 11). The role of additives, which had beneficial effects on regioselectivity in our related oxacycle study, was next examined 3. The use of boric acid or B(OMe) 3 entirely prevented the formation of 6 a , but required higher temperatures for full conversion and led to decreased stereoselectivity (Table 1, entries 12 and 13); lowering of the temperature improved matters, but the reaction under these conditions was capricious on larger scales (Table 1, entry 14).…”

KOAc-promoted alkynylation of α-C–H bonds of ethers with alkynyl bromides under transition-metal-free conditions

“…4k Pd-catalyzed synthesis of 2-alkynyl oxacycles from their cyclic and acyclic carbonates. 16 Encouraged by the above transformations, and in continuation of our and others interests in transformation of C(sp 3 )-H bond into C(sp 3 )-C bond, 17 we conceived that alkynylation of α-5 position C-H bond of ethers with alkynyl bromides without the assistance of transition metal may be possible. Herein, we wish to report an efficient reaction of alkynyl bromides with cyclic ethers for direct C(sp)-C(sp 3 ) bond formation through KOAc-promoted α-position C-H activation and alkynylation of ethers under 10 transition-metal-free and simple reaction conditions (Scheme 1).…”

A Second‐Generation Total Synthesis of Spirastrellolide A Methyl Ester

“…Treatment of triol 17 with triphosgene to selectively generate the C37-C40 cyclic carbonate, followed by oxidation of the remaining alcohol at C1, afforded the C1-C42 carboxylic acid 5, ready for the planned p-allyl Stille cross-coupling reaction. [18] Following optimization in model studies, [10b] we were pleased to observe the smooth coupling of 5 with the C43-C47 stannane 4 using catalytic [PdCl 2 (MeCN) 2 ] in wet DMF, which afforded C1-C47 diene 3 as a single E,Z isomer in 86 % yield. Notably, this protocol for assembling the full spirastrellolide side chain on a linear intermediate was found to be significantly more efficient than our earlier route using olefin cross-metathesis in the presence of the sterically demanding macrolactone core.…”