Enantio‐ and Diastereoselective Dehydrative “One‐Step” Construction of Spirocarbocycles via a Ru/H⁺‐Catalyzed Tsuji–Trost Approach

Abstract

Chiral spirocarbocyclic skeletons are ubiquitous in natural products. An intramolecular Tsuji-Trost (T-T) α-allylation of simple cyclic ketones is a reasonable approach to construct chiral spriocarbocyclic motifs; however, it has been a challenging approach despite many excellent intermolecular examples. For the first time, this has been achieved by a Ru/H combined catalyst that dehydratively cyclizes racemic allylic alcohols comprising a simple ketone via simultaneous activation of the C=O and OH groups. This chiral technology facilitates the construction of various spirocarbocycles containing two contiguous spiro all-carbon quaternary and tertiary stereocenters. Among four possible stereoisomers, one stereoisomer can be selectively produced in high yield, enhancing the feasibility of the T-T strategy, particularly in the synthesis of spirocarbocycles.

Asymmetric Dehydrative Allylation Using Soft Ruthenium and Hard Brønsted Acid Combined Catalyst

“…The significant difference may be caused by a double hydrogen bond between the OH group and XSO 3 H, as shown in Figure 13. The complex with X=CH 3 was calculated to be 1.3 kcal mol −1 more stable than that with X=CF 3 [31] …”

“…Figure 15 shows the results obtained for the reaction of E allylic alcohol (±)‐ 35 a leading to the formation of 36 a under standard conditions: [(±)‐ 35 a ]=200 mM; [( S , S )‐ 26 ]=[X 1 H]=2 mM (1 mol %); [X 2 H]=0–8 mM (0–4 mol %); toluene or 1,2‐dichloroethane (DCE); reflux; 1 h [31] . A 1 : 1 combination of ( S , S )‐ 26 and p ‐TsOH (X 1 H), which efficiently catalyzes the intramolecular allylation of 1,3‐dicarbonyl compounds, was not effective.…”

“…The complex with X=CH 3 was calculated to be 1.3 kcal mol À 1 more stable than that with X=CF 3 . [31] Figure 14 shows the application of the present catalysis to the asymmetric cyclization of C-, N-, and O-nucleophiles. Nearly optically pure carbocyclic compounds and saturated Nand O-heterocycles can be obtained.…”

“…Figure 15 shows the results obtained for the reaction of E allylic alcohol (�)-35 a leading to the formation of 36 a under standard conditions: [(�)-35 a] = 200 mM; [(S,S)-26] = [X 1 H] = 2 mM (1 mol %); [X 2 H] = 0-8 mM (0-4 mol %); toluene or 1,2-dichloroethane (DCE); reflux; 1 h. [31] A 1 : 1 combination of (S,S)-26 and p-TsOH (X 1 H), which efficiently catalyzes the intramolecular allylation of 1,3-dicarbonyl com- A combination of (S,S)-26 and p-TsOH in a 1 : 5 ratio in toluene or DCE was used for the substrate scope (Figure 16). Introduction of a CH 3 substituent at C(2) of the allylic alcohol moiety of 35 a decreased the reactivity by one order of magnitude, but produced 36 b in 99 : 1 dr and 99 : 1 er with a C(3)-methyl substituted substrate, and a diene was the major product.…”

“…For example, "acid X 1 H" activates the OH group to generate an electrophilic π-allyl metal complex in the presence of an appropriate low-valence metal complex; "acid X 2 H" activates the C=O group to facilitate enol formation. These two acids may be identical or different.Figure15shows the results obtained for the reaction of E allylic alcohol (�)-35 a leading to the formation of 36 a under standard conditions: [(�)-35 a] = 200 mM; [(S,S)-26] = [X 1 H] = 2 mM (1 mol %); [X 2 H] = 0-8 mM (0-4 mol %); toluene or 1,2-dichloroethane (DCE); reflux; 1 h [31]. A 1 : 1 combination of (S,S)-26 and p-TsOH (X 1 H), which efficiently catalyzes the intramolecular allylation of 1,3-dicarbonyl com-…”