Total syntheses via cyclopropanols

Total Syntheses of Rhodomolleins XX and XXII: A Reductive Epoxide‐Opening/Beckwith–Dowd Approach

“…Further deprotection in the presence of PPTS furnished rhodomollein XX (5)in64% yield over three steps.S ynthetic 5 and 6 exhibited 1 Ha nd 13 CNMR spectra identical in all respects to those reported for the natural products. [29] On the basis of seminal works by DePuy,Saegusa, and Narasaka, [30] it was found that the cleavage of the C13-C16 bond could be significantly inhibited in the presence of Fe(NO 3 ) 3 and 1,4cyclohexadiene in DMF, [31] affording a5.4:1 mixture of 9 and 24 in 83 %y ield (conditions a). [29] On the basis of seminal works by DePuy,Saegusa, and Narasaka, [30] it was found that the cleavage of the C13-C16 bond could be significantly inhibited in the presence of Fe(NO 3 ) 3 and 1,4cyclohexadiene in DMF, [31] affording a5.4:1 mixture of 9 and 24 in 83 %y ield (conditions a).…”

Copper‐Catalyzed Aerobic Oxidative Cyclization Cascade to Construct Bridged Skeletons: Total Synthesis of (−)‐Suaveoline

“…We envisioned that catalytic tandem CÀHo xidation and cyclopropanol ring-opening cyclization [10,11] of 2 could give the azabicyclo[3.3.1]nonane 4 with ak etone functionality, ideally,u sing as ingle catalyst to catalyze both the two elementary steps and air as the oxidant (Scheme 1c). This proposal has several potential advantages.C hiral cyclopropanol 2 with ad ictating stereogenic carbon center can be conveniently prepared in one step by Kulinkovich cyclopropanation of ester 1, [10a] which can be easily prepared from amino acids in two steps.T he great advances in the area of cross-dehydrogenative coupling (CDC) of tetrahydroisoquinoline with nucleophiles made by Li, Murahashi, Wang, Liu, and others indicate the feasibility of the initial CÀHoxidation step to generate iminium ion 3.…”

“…This proposal has several potential advantages.C hiral cyclopropanol 2 with ad ictating stereogenic carbon center can be conveniently prepared in one step by Kulinkovich cyclopropanation of ester 1, [10a] which can be easily prepared from amino acids in two steps.T he great advances in the area of cross-dehydrogenative coupling (CDC) of tetrahydroisoquinoline with nucleophiles made by Li, Murahashi, Wang, Liu, and others indicate the feasibility of the initial CÀHoxidation step to generate iminium ion 3. [10,11] Structurally,the flat N-aryl group of 2 first functions to facilitate the initial CÀHo xidation, and then to force the cyclopropanol group to take ap seudo-axial orientation prerequisite for cyclization to the iminium ion to minimize the A 1,2 -strain, [13a] while the homologous A 1,3 -strain controlling factor is more often used to construct bridged structures. [10,11] Structurally,the flat N-aryl group of 2 first functions to facilitate the initial CÀHo xidation, and then to force the cyclopropanol group to take ap seudo-axial orientation prerequisite for cyclization to the iminium ion to minimize the A 1,2 -strain, [13a] while the homologous A 1,3 -strain controlling factor is more often used to construct bridged structures.…”

“…[10,11] Structurally,the flat N-aryl group of 2 first functions to facilitate the initial CÀHo xidation, and then to force the cyclopropanol group to take ap seudo-axial orientation prerequisite for cyclization to the iminium ion to minimize the A 1,2 -strain, [13a] while the homologous A 1,3 -strain controlling factor is more often used to construct bridged structures. [10,11] Second, most of the existing C À Hf unctionalizations of tetrahydroisoquinoline-type compounds are limited to intermolecular reactions with common nucleophiles, and there are no precedents for the formation of bridged structures. First, successful examples of electrophilic trapping of cyclopropanol with carbonyl compounds remain scarce,and nucleophilic addition to iminium ions or imines has not been reported, other than in the formation of ac hallenging bridged structure.…”

“…First, successful examples of electrophilic trapping of cyclopropanol with carbonyl compounds remain scarce,and nucleophilic addition to iminium ions or imines has not been reported, other than in the formation of ac hallenging bridged structure. [10,11] Thek ey to the success of this proposal is to identify amultifunctional catalytic system that can catalyze the initial CÀHoxidation step without prematurely interfering with the labile cyclopropanol unit, and, more importantly,iscapable of promoting the unexplored cyclopropanol ring-opening addition to the in situ formed iminium ion. [12] Third, cyclopropanol is prone to react under oxidative conditions,which could result in complications.…”