Asymmetric [4 + 3] Cycloadditions between Vinylcarbenoids and Dienes: Application to the Total Synthesis of the Natural Product (−)-5-epi-Vibsanin E

Abstract

The total synthesis of (−)-5-epi-vibsanin E (2) has been achieved in 18 steps. The synthesis combines the rhodium-catalyzed [4 + 3] cycloaddition between a vinylcarbenoid and a diene to rapidly generate the tricyclic core with an effective end game strategy to introduce the remaining side-chains. The [4 + 3] cycloaddition occurs by a cyclopropanation to form a divinylcyclopropane followed by a Cope rearrangement to form a cycloheptadiene. The quaternary stereogenic center generated in the process can be obtained with high asymmetric induction when the reaction is catalyzed by the chiral dirhodium complex, Rh2(S-PTAD)4.

Total Synthesis of (±)‐Scopolamine: Challenges of the Tropane Ring

“…Diazo esters 11 were obtained from acetoacetates 10 in 89 % to quantitative yield using 4-acetamidobenzenesulfonyl azide (p-ABSA) as a safe diazo transfer agent (Scheme 1). [17,18] TBS enol ethers 9 were obtained in quantitative yield from esters 11. Application of Davies' conditions to methyl ester 9a furnished the desired product 12a in 53 % yield (Table 1, Entry 1).…”

“…[30,31] Our second retrosynthetic approach to 4 involved the elimination of the hydroxy group in 6-hydroxytropinone (16) to generate the 6,7-double bond ( Figure 4). Alcohol 16 would be obtained by a modified Robinson-Schöpf reaction using hydroxysuccinaldehyde (17). [32,33] Thus, a modified Robinson reaction using commercial 2,5-dimethoxy-2,5-dihydrofuran (18) as the hydroxysuccinaldehyde precursor was carried out to form 6-hydroxytropinone (16) in 30 % yield (Scheme 3).…”

Catalytic enantioselective synthesis of quaternary carbon stereocentres

“…In their synthesis of (−)-5- epi -vibsanin E, the Davies group illustrates one variant: a cyclopropanation/Cope rearrangement sequence. 21 In the example illustrated, cycloaddition of the vinylcarbenoid derived from vinyl diazoester 21 and Rh 2 ( R -PTAD) 4 with the terminal double bond of diene 20 delivered cis -divinylcyclopropane 22 , which under the reaction conditions underwent Cope rearrangement to furnish cycloheptadiene 23 (Fig. 3c).…”

“…The first step in this sequence is Rh-catalyzed cyclopropanation of the terminal double bond of the acyclic triene to form divinyl cyclopropane 22 , which upon in situ Cope rearrangement generates 23 and its quaternary stereocenter. Product 23 was employed in the total synthesis of the diterpenoid (−)-5- epi -vibsanin E. 21 Me, methyl; TBS, tert -butyldimethylsilyl.…”

Ene-yne Cross-Metathesis for the Preparation of 2,3-Diaryl-1,3-dienes

“…Besides the classical [4 + 2] cycloadditions, 1,3-butadiene itself and aliphatic 1,3-butadiene substrates have been efficiently transformed via transition metal-catalyzed reactions. Among them, ruthenium-catalyzed addition of aldehydes [5] and olefin metathesis [6], nickel-catalyzed multicomponent coupling with alkynes or aldehydes and dimethylzinc in the presence of carbon dioxide [7,8], rhodium-catalyzed asymmetric [4 + 3] cycloaddition with vinylcarbenoids [9], palladium-catalyzed telomerization with various nucleophiles [10][11][12], hydroamination [13,14] and hydroamidocarbonylation [15], are representative examples. However, monoarylated 1,3-dienes have been used for triflic acid-catalyzed synthesis of indenes [16], ruthenium-catalyzed isomerization [17], palladium-catalyzed hydroarylation with boronic esters [18], cobalt-catalyzed hydrosilylation [19], asymmetric hydrovinylation with ethylene [20] and enantioselective cycloaddition with internal alkynes [21].…”