Gold-Catalyzed Deoxygenative Nazarov Cyclization of 2,4-Dien-1-als for Stereoselective Synthesis of Highly Substituted Cyclopentenes

Abstract

Treatment of 2,4-dien-1-als with allylsilanes and PPh(3)AuSbF(6) (3 mol %) led to formation of 1,4-bis(allyl)cyclopentenyl products; this gold catalyst is superior to commonly used Lewis acids according to catalyst screening. Such gold-catalyzed deoxygenative cyclizations are compatible with various oxygen-, amine-, sulfur-, hydrogen-, and carbon-based nucleophiles. The value of this new catalysis is demonstrated by the diverse annulations of 2,4-dien-1-als with electron-rich alkenes and arenes, providing an easy access to complicated cyclopentenyl frameworks. Structural analysis of annulation products reveals evidence for the participation of Nazarov cyclization. This deoxygenative cyclization is extensible to a tandem intramolecular cyclization/nucleophilic addition cascade, giving polycyclic carbo- or oxacyclic compounds with controlled stereochemistry. This new gold catalysis is applied to a short synthesis of natural compounds of the brazilane family, including brazilane, O-trimethyl-, and O-tetramethyl brazilane.

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

“…(+)-Brazilin ( 1 ) and (−)-haematoxylin ( 2 ) are two structurally-related tetracyclic homoisoflavonoid (containing a chroman unit) natural products (Fig. 1) [2–4]. Their synthetic des-(angular)hydroxy derivatives (+)-brazilane ( 3 ) and haematoxylane ( 4 ) have also been mentioned in the literature [2–4].…”

“…1) [2–4]. Their synthetic des-(angular)hydroxy derivatives (+)-brazilane ( 3 ) and haematoxylane ( 4 ) have also been mentioned in the literature [2–4]. Among them, brazilin ( 1 ), the most-studied member of this group, has been proved to have a number of potentially important biological activities including the abilities to act as telomerase inhibitor and to produce DNA nicks [5–7].…”

Theoretical Studies on Pentadienyl Cation Electrocyclizations

“…The unsubstituted pentadienyl cation has been shown to prefer the all trans conformation 1 to the all cis 2 by 8 kcal/mol (HF/3-21G; Fig. [4] Rocaglamide [6] 15-deoxy-12-hydroxy-10-(trifluoromethyl)-7 -PGA 1 [5] Photodeoxytridachione [3] H H H 9, (12) Capnellene [2] O HO HO OH Brazilane [7] O (CH 2 ) 5 CO 2 Me HO C 6 H 13 . From the productive cis conformation, the barrier for cyclization is predicted to range from ~1-15 kcal/mol, depending on the theoretical method used [10][11][12][13][14].…”

Catalytic Nazarov Cyclization: The State of the Art

“…[2] This transformation has received tremendous attention in the field of organic synthesis due to its ability to form synthetically versatile cyclopentenones. [3][4][5][6][7][8][9][10][11][12][13][14][15] With appropriately substituted dienones, the orbital reorganization implants new stereocenters in the oxyallyl cation (3), which are retained in the pentacyclic product (5).…”