Palladium-catalyzed allylic substitution of secondary allylic esters with ketone enolates

Kinouchi, Wataru; Saeki, Ryohei; Kawashima, Hidehisa; Kobayashi, Yuichi

doi:10.1016/j.tetlet.2015.03.063

Cited by 11 publications

(8 citation statements)

References 36 publications

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“…The product was extracted with EtOAc and purified by chromatography on silica gel (hexane/EtOAc) to give 21a (416 mg, 91% yield): 97.9% ee by HPLC (Chiralcel OD‐H, hexane/ i PrOH = 99:1, 1.0 mL/min, 35 °C, t R /min = 8.99 ( R ‐isomer, minor), 9.91 ( S ‐isomer, major)); liquid; R f 0.81 (CH 2 Cl 2 /acetone, 3:1), 0.30 (hexane/EtOAc, 5:1); [ α ] D 21 = –4 ( c = 1.1, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ) δ = 0.07 (s, 6 H), 0.91 (s, 9 H), 1.27 (d, J = 6.0 Hz, 3 H), 1.46 (br s, 1 H), 4.10–4.23 (m, 2 H), 4.29–4.37 (m, 1 H), 5.69–5.80 (m, 2 H); 13 C–APT NMR (100 MHz, CDCl 3 ) δ –5.2 (+), 18.5 (–), 23.3 (+), 26.0 (+), 63.2 (–), 68.3 (+), 129.2 (+), 134.1 (+). The 1 H and 13 C NMR spectra were identical with those reported …”

Section: Methodssupporting

confidence: 75%

“…( S , E )‐5‐[( tert ‐Butyldimethylsilyl)oxy]pent‐3‐en‐2‐ol (21a): According to the procedure developed for racemic 3‐butyn‐2‐ol, a mixture of ( S )‐3‐butyn‐2‐ol ( 20 ) (0.627 mL, 8.00 mmol) (Aldrich,% ee of the derived compound was determined at a later stage) and a solution of n BuLi (1.60 M in hexane, 15 mL, 24.0 mmol) in THF (40 mL) was stirred at 0 °C for 30 min, and paraformaldehyde (820 mg, 27 mmol) was added. The mixture was stirred at rt for 15 h and diluted with saturated NH 4 Cl.…”

Section: Methodsmentioning

confidence: 99%

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S_N2 Reaction of Diarylmethyl Anions at Secondary Alkyl and Cycloalkyl Carbons

et al. 2019

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The substitution reaction of the diethyl allylic and propargylic phosphates with Ar2CH anions was applied to sec‐alkyl phosphates to compare reactivity and stereoselectivity. However, the substitution took place on the ethyl carbon of the diethyl phosphate group. We then found that the diphenyl phosphate leaving group ((PhO)2PO2) was suited for the substitution at the sec‐alkyl carbon. Enantioenriched diphenyl sec‐alkyl phosphates with different substituents (Me, Et, iPr) on the vicinal position underwent the substitution reaction with almost complete inversion (>99% enantiospecificity). The substitution reactions of cyclohexyl phosphates possessing cis or trans substituents (Me and/or tBu) at the C4, C3, and C2 positions of the cyclohexane ring were also studied to observe the difference in reactivity among the cis and trans isomers. A transition‐state model with the phosphate leaving group ((PhO)2PO2) in the axial position was proposed to explain the difference. This model was supported by computational calculation of the virtual substitution reaction of the structurally simpler “dimethyl” cyclohexyl phosphates (leaving group = (MeO)2PO2) with MeLi. Furthermore, the calculation unexpectedly indicated higher propensity of (PhO)2PO2 as a leaving reactivity than alkyl phosphate groups such as (MeO)2PO2 and (iPrO)2PO2.

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Section: Methodssupporting

confidence: 75%

Section: Methodsmentioning

confidence: 99%

S_N2 Reaction of Diarylmethyl Anions at Secondary Alkyl and Cycloalkyl Carbons

et al. 2019

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“…Further simplification of 10 by asymmetric Cu-catalyzed Grignard alkylations and aWittig olefination delivered diacetate 11.The 5-6 ring motif of 11 was disconnected at the CÀC-bond joining the two carbocycles. [16] We realized that for this challenging transformation an advanced intermolecular Pd-catalyzed asymmetric allylic alkylation could be instrumental, inspired by the work of Tr ost. [17] By this,w ea rrived at building blocks 13 and 14, Scheme 1.…”

Section: Resultsmentioning

confidence: 99%

“…Further simplification of 10 by asymmetric Cu‐catalyzed Grignard alkylations and a Wittig olefination delivered diacetate 11 . The 5–6 ring motif of 11 was disconnected at the C−C‐bond joining the two carbocycles [16] …”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of the Alleged Structure of Crenarchaeol Enables Structure Revision**

et al. 2021

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Crenarchaeol is a glycerol dialkyl glycerol tetraether lipid produced exclusively in Archaea of the phylum Thaumarchaeota. This membrane-spanning lipid is undoubtedly the structurally most sophisticated of all known archaeal lipids and an iconic molecule in organic geochemistry. The 66-membered macrocycle possesses a unique chemical structure featuring 22 mostly remote stereocenters, and a cyclohexane ring connected by a single bond to a cyclopentane ring. Herein we report the first total synthesis of the proposed structure of crenarchaeol. Comparison with natural crenarchaeol allowed us to propose a revised structure of crenarchaeol, wherein one of the 22 stereocenters is inverted.

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“…The oxidative addition of a 1,1,2‐trisubstituted allylic ester should be even less favored thermodynamically because trisubstituted allylic electrophiles are sterically more hindered and would bind more weakly to the iridium than would a 1,2‐disubstituted allylic electrophile. At the same time, it is known that the leaving group in the allyl electrophile influences the rate, and presumably thermodynamics, for oxidative addition ,. Thus, we hypothesize that the identity of the leaving group and the nucleophile are crucial to observing these first enantioselective reactions of disubstituted allylic esters because the better leaving group makes the reversible oxidative addition step more favored thermodynamically and the high nucleophilicity of the dioxinone effectively traps the small concentration of the allyliridium intermediate.…”

Section: Figurementioning

confidence: 88%

Iridium‐Catalyzed Regio‐ and Enantioselective Allylic Substitution of Trisubstituted Allylic Electrophiles

Chen

Hartwig

2016

Angewandte Chemie

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The first Ir-catalyzed enantioselective allylation of trisubstituted allylic electrophiles has been developed. Through modification of the leaving group of allylic electrophiles, we found that trisubstituted allylic phosphates are suitable electrophiles for asymmetric allylation. The reaction of allylic phosphates with enol silanes derived from dioxinones gave allylated products in good yields with high enantioselectivities. Graphical AbstractThe first Ir-catalyzed enantioselective allylic substitution of trisubstituted allylic electrophiles has been developed. By employing allylic phosphates as electrophiles, asymmetric allylic substitution of enol silanes derived from dioxinones gave allylated products in good yields with high enantioselectivities. KeywordsIr-catalyzed asymmetric allylic substitution; trisubstituted allylic electrophiles; allylic phosphates; 1,1'-substituted olefin; dioxinone Iridium-catalyzed, enantioselective allylic substitution has become a powerful method to access highly enantioenriched molecules. 1,2 This class of reaction began to occur in high yield and ee when a metalacyclic catalyst derived from a phosphoramidite ligand was developed. Over the past decade, research with these catalysts has focused on assessing and increasing the scope of nucleophile. In this body of work, cinnamyl carbonates and, in some cases, aliphatic allylic carbonates have been used as electrophiles. With few exceptions, 3 these carbonates contain one aryl, alkyl or vinyl substituent and one leaving group to generate products in which the terminal alkene unit contains a single substituent ( Figure 1). [4][5][6][7] The inability to use allylic electrophiles containing more than one substituent, besides the leaving group, in asymmetric allylic substitutions is a major limitation on the eventual Correspondence to: John F. Hartwig. HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript application of such reactions to the syntheses of complex molecules. In the current work, we have sought to develop systems that allow asymmetric allylic substitutions to occur with allylic electrophiles that are more substituted than those used previously, while maintaining the high regioselectivity for formation of branched products that characterizes iridiumcatalyzed allylic substitution. In particular, we have sought to develop systems for asymmetric reactions of allylic esters containing 1,2-disubstituted alkene units to form products containing 1,1'-disubstituted olefins. Under the standard conditions comprising a carbonate leaving group and cyclometalated catalyst derived from a phosphoramidite, such reactions do not occur. This lack of reactivity is consistent with the absence of such reactions in the prior publications and highlights the need to find combinations of catalyst, leaving group, and nucleophile that will enable such processes.Here, we report the first Ir-catalyzed, enantioselective allylic substitution of a trisubstituted allylic electrophile. By using a phosphate as the...

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Palladium-catalyzed allylic substitution of secondary allylic esters with ketone enolates

Cited by 11 publications

References 36 publications

S_N2 Reaction of Diarylmethyl Anions at Secondary Alkyl and Cycloalkyl Carbons

S_N2 Reaction of Diarylmethyl Anions at Secondary Alkyl and Cycloalkyl Carbons

Total Synthesis of the Alleged Structure of Crenarchaeol Enables Structure Revision**

Iridium‐Catalyzed Regio‐ and Enantioselective Allylic Substitution of Trisubstituted Allylic Electrophiles

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Palladium-catalyzed allylic substitution of secondary allylic esters with ketone enolates

Cited by 11 publications

References 36 publications

SN2 Reaction of Diarylmethyl Anions at Secondary Alkyl and Cycloalkyl Carbons

SN2 Reaction of Diarylmethyl Anions at Secondary Alkyl and Cycloalkyl Carbons

Total Synthesis of the Alleged Structure of Crenarchaeol Enables Structure Revision**

Iridium‐Catalyzed Regio‐ and Enantioselective Allylic Substitution of Trisubstituted Allylic Electrophiles

Contact Info

Product

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S_N2 Reaction of Diarylmethyl Anions at Secondary Alkyl and Cycloalkyl Carbons

S_N2 Reaction of Diarylmethyl Anions at Secondary Alkyl and Cycloalkyl Carbons