Enantioselective One-Pot Rhodium-Catalyzed Cycloisomerization-Wittig Sequence to Chiral Functionalized 4-Alkyl 3-Alkylidene Tetrahydrofuran(on)es

Abstract

Alkyl and (hetero)aryl alkyne allyl alcohols can readily be transformed into chiral 4-alkyl 3-alkylidene tetrahydrofurans and tetrahydrofuranones bearing a,b-unsaturated carbonyl side chains in a one-pot fashion via an enantioselective rhodium-catalyzed cycloisomerization-Wittig olefination sequence in good yields (54-86%).Synthetic efficiency represents a main objective within novel methodology and reaction design. The combination of several elementary reaction steps within a one-pot process features great economic and ecological potential as well as a crucial challenge. Naturally, the spotlight is turned on the combination of transformations dealing with exceptionally mild reaction conditions. Above all, transition-metal catalyses take in a predestined role in this context, especially if they can be directed in a domino fashion generating a suitable reactive functionality en route. Among numerous transition-metal-catalyzed cyclizations, cycloisomerization of 1,6-enynes 1 has become an outstanding tool to form cycles bearing a 1,4-diene functionality. In case of alkyne allyl alcohols the cycloisomerization reaction ultimately leads to g,d-enals due to the tautomerism of the elusive dienol intermediate. These resulting enals set the stage for consecutive transformations, for example, conversion of the reactive carbonyl functionality, in a one-pot fashion (Scheme 1).As part of our program to design new transition-metalcatalyzed sequences initiated by intramolecular cycloisomerization, we are particularly interested in sequential one-pot processes. Within our studies we have already established a variety of palladium-and iridium-catalyzed cycloisomerization sequences, 2 notably a Pd-catalyzed cycloisomerization-Wittig olefination sequence. 3 Both the Pd-and the Ir-catalyzed cycloisomerization are limited with respect to the substitution pattern at the alkyne position. Dealing with Pd 2 (dba) 3 ·CHCl 3 as a catalyst precursor, the reaction works very well for TMS-substituted alkyne allyl alcohols whereas the Ir-catalyzed version shows a complementary behavior transforming only arylsubstituted alkyne allyl alcohols. However, as a main drawback both routes just furnish the racemic enal products.Scheme 1 Rhodium-catalyzed cycloisomerization as an entry to sequential transformationsThe rhodium(I)-catalyzed cycloisomerization reaction, 4 firstly published by Zhang, 5 enables a highly effective and enantioselective access to cyclic five-membered-ring systems. 6 The transformation of linear 1,6-enynes proceeds by application of chiral cationic rhodium complexes with enantiomerically pure chelating bisphosphane ligands, preferably BINAP, 7 delivering the corresponding enals with excellent levels of enantioselectivity. The configuration of the newly established stereogenic center was determined by anomalous X-ray crystal diffraction 8 and indirectly by diastereoselective kinetic resolution. 9 Just recently, we have reported on the rhodium-catalyzed cycloisomerization of alkyne allyl alcohols and first examples of subsequent...

A DFT study on the reaction mechanism of the gold(I)‐catalyzed cycloisomerization of alkynylhydroxyallylamides to 4‐Oxa‐6‐azatricyclo[3.3.0.02,8]octane and 3‐Acyl‐4‐alkenylpyrrolidine

“…Alkyne allyl alcohols (AAAs), a specific class of 1,6-enynes, have been utilized as starting materials in transition metal-catalyzed cycloisomerization reactions. Various transition metals, including rhodium [3][4][5], iridium [6], and palladium [7][8][9][10], have been employed as catalyst species for such transformations. In all cases, the cycloisomerization reactions resulted in Alder-ene-type products (Scheme 2).…”