A Novel Tandem Cyclization of 2,7- or 2,8-Bis-Unsaturated Esters Mediated by (η2-Propene)TiX2 (X = Cl or O-i-Pr). A Facile Construction of Bicyclo[3.3.0]octane, -[4.3.0]nonane, and -[3.1.0]hexane Skeletons

Suzuki, Ken; Urabe, and Hirokazu; Sato, Fumie

doi:10.1021/ja961928n

Cited by 60 publications

(21 citation statements)

References 13 publications

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“…Gratifyingly, the cyclization proceeds smoothly with the ester group remaining intact to give the titanabicycle 5 as a reasonably stable species. In some cases, the cyclization of 4 was followed by some novel transformations that were more than what we had expected …”

Section: Introductionmentioning

confidence: 98%

Intramolecular Cyclization of 2,7- or 2,8-Bis-unsaturated Esters Mediated by (η²-Propene)Ti(O-i-Pr)₂. Facile Construction of Mono- and Bicyclic Skeletons with Stereoselective Introduction of a Side Chain. A Synthesis of d-Sabinene

1997

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tert-Butyl 2-en-7-ynoate 6 was treated with (η2-propene)Ti(O-i-Pr)2 (3), generated in situ from Ti(O-i-Pr)4 or Ti(O-i-Pr)3Cl and i-PrMgCl, in ether at −50 to −20 °C to afford the product 8 in good yield. The presence of the intermediate titanabicycle 7 was verified by bis-deuterolysis with excess D2O. When the titanabicycle 7 was treated with 1.1 equiv of i-PrOD and then worked up as usual, the monodeuterated product 10 was obtained with high site selectivity and stereoselectivity. Other electrophiles such as aldehydes and ketones also reacted with the titanabicycle in a highly stereoselective manner to give cyclopentanes having a stereo-defined side chain. On the contrary, treatment of the corresponding ethyl ester, ethyl 8-(trimethylsilyl)-(E)-2-octen-7-ynoate (28), with 3 under the same conditions followed by the addition of 1.1 equiv of s-BuOH afforded 2-(trimethylsilyl)-1-bicyclo[3.3.0]octen-3-one (32) in 80% yield. Quenching the same reaction mixture with i-PrOD, EtCHO, and Et2CO in place of s-BuOH gave 4-deuterio (with exclusive deuterium incorporation), 4-(1-hydroxypropyl), and 4-(1-ethyl-1-hydroxypropyl) derivatives of the above bicyclic ketone (34, 35, and 36) in good yields. These electrophiles were always introduced from the convex face of the bicyclic skeleton. The stereochemistry of the cyclization could be controlled by an allylic substituent such as (tert-butyl)dimethylsiloxy or butyl group to a high degree yet with a reversal diastereoselection to give 45 or 47. The reaction of ethyl 7-octen-2-ynoate (56) and 3 at −50 to 0 °C took place in a quite different way to afford 1-[(ethoxycarbonyl)methyl]bicyclo[3.1.0]hexane (64) in 74% yield after hydrolysis. If the simple hydrolysis is replaced by deuterolysis or the action of diethyl ketone, 1-[(ethoxycarbonyl)dideuteriomethyl] (with 99% deuterium incorporation), or 1-[(ethoxycarbonyl)(3-pentylidene)methyl] derivative of the above product (65 or 66) was obtained in good yields. A 7-en-2-ynoate having an internal Z-double bond such as 80 afforded a single stereoisomer 82 with the substituent at the endo position of the bicyclic skeleton, suggesting that the stereochemical integrity of the Z-double bond of the starting material was retained in the product. An alkyl substituent at the allylic position of the substrates like 74 and 76 nicely controlled the stereochemistry of the cyclization to afford single products 75 and 77 with the substituent being placed in the exo orientation of the bicyclic structure. This high diastereoselectivity was successfully applied to an enantioselective synthesis of d-sabinene from an optically active enynoate via nearly complete chirality transfer.

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Section: Introductionmentioning

confidence: 98%

Intramolecular Cyclization of 2,7- or 2,8-Bis-unsaturated Esters Mediated by (η²-Propene)Ti(O-i-Pr)₂. Facile Construction of Mono- and Bicyclic Skeletons with Stereoselective Introduction of a Side Chain. A Synthesis of d-Sabinene

1997

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“…Remarkably, by shutting down the β -H elimination process, the azatitanacyclohexene IIId collapses via attack of the α -C on the γ -C, 13 resulting in reductive elimination of an α -imino functionalized cyclopropane. In fact, this cyclopropanation can also be observed when using the deuterated analogue 1b : because β -D elimination (which must occur in 1b ) is typically slower than β -H elimination (in 1a ), there should be a larger k rel for forming the cyclopropane 3 versus the α , β -unsaturated imine 2 in the reaction of 1b .…”

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confidence: 99%

Ti-Catalyzed Multicomponent Oxidative Carboamination of Alkynes with Alkenes and Diazenes

2016

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The inter- or intramolecular oxidative carboamination of alkynes catalyzed by [py2TiCl2NPh]2 is reported. These multicomponent reactions couple alkenes, alkynes and diazenes to form either α,β-unsaturated imines or α-(iminomethyl)cyclopropanes via a TiII/TiIV redox cycle. Each of these products is formed from a common azatitanacyclohexene intermediate that undergoes either β-H elimination or α,γ-coupling, wherein the selectivity is under substrate control.

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“…Stereoselective trapping and/or cyclization of enynes bearing one polarized p-bond (Scheme 17): Enyne substrates bearing an enoate are substrates for Ti(Oi-Pr) 4 /2i-PrMgCl-mediated ring closure, and these electronically activated systems deliver titanacyclopentene intermediates that have the potential to engage in a different collection of C-C bond-forming processes. 48,49 Illustrated in Scheme 17A, enyne cyclization followed by addition of formaldehyde delivers a carbocyclic product with high levels of stereoselection. Here, the site of aldehyde addition is different than that previously discussed in Scheme 15A, likely due to the reactivity profile imparted to the ring-expanded titanium enolate intermediate.…”

Section: Ti-alkoxide-promoted Enyne Cyclizationmentioning

confidence: 99%

“…As illustrated in Scheme 18, if the polarized p-bond in the enyne is the alkyne (in the form of an alkynoate), a different reaction path is observed. 48 (to generate an epoxy-oxatitanacycloheptene intermediate), followed by rearrangement to the corresponding oxatitanacyclohexene, and a second intramolecular nucleophilic addition of the remaining s C-Ti bond to the pendant ketone. Based on the stereoselective course of the initial carbometalation process (generating the first metallacyclopentene intermediate), the subsequent steps proceed in a highly stereocontrolled manner -no evidence was found for the production of isomeric products.…”

Section: Ti-alkoxide-promoted Enyne Cyclizationmentioning

confidence: 99%

5.34 Early Transition Metal Mediated Reductive Coupling Reactions

Micalizio¹

2014

Comprehensive Organic Synthesis II

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A Novel Tandem Cyclization of 2,7- or 2,8-Bis-Unsaturated Esters Mediated by (η²-Propene)TiX₂ (X = Cl or O-i-Pr). A Facile Construction of Bicyclo[3.3.0]octane, -[4.3.0]nonane, and -[3.1.0]hexane Skeletons

Cited by 60 publications

References 13 publications

Intramolecular Cyclization of 2,7- or 2,8-Bis-unsaturated Esters Mediated by (η²-Propene)Ti(O-i-Pr)₂. Facile Construction of Mono- and Bicyclic Skeletons with Stereoselective Introduction of a Side Chain. A Synthesis of d-Sabinene

Intramolecular Cyclization of 2,7- or 2,8-Bis-unsaturated Esters Mediated by (η²-Propene)Ti(O-i-Pr)₂. Facile Construction of Mono- and Bicyclic Skeletons with Stereoselective Introduction of a Side Chain. A Synthesis of d-Sabinene

Ti-Catalyzed Multicomponent Oxidative Carboamination of Alkynes with Alkenes and Diazenes

5.34 Early Transition Metal Mediated Reductive Coupling Reactions

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A Novel Tandem Cyclization of 2,7- or 2,8-Bis-Unsaturated Esters Mediated by (η2-Propene)TiX2 (X = Cl or O-i-Pr). A Facile Construction of Bicyclo[3.3.0]octane, -[4.3.0]nonane, and -[3.1.0]hexane Skeletons

Cited by 60 publications

References 13 publications

Intramolecular Cyclization of 2,7- or 2,8-Bis-unsaturated Esters Mediated by (η2-Propene)Ti(O-i-Pr)2. Facile Construction of Mono- and Bicyclic Skeletons with Stereoselective Introduction of a Side Chain. A Synthesis of d-Sabinene

Intramolecular Cyclization of 2,7- or 2,8-Bis-unsaturated Esters Mediated by (η2-Propene)Ti(O-i-Pr)2. Facile Construction of Mono- and Bicyclic Skeletons with Stereoselective Introduction of a Side Chain. A Synthesis of d-Sabinene

Ti-Catalyzed Multicomponent Oxidative Carboamination of Alkynes with Alkenes and Diazenes

5.34 Early Transition Metal Mediated Reductive Coupling Reactions

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A Novel Tandem Cyclization of 2,7- or 2,8-Bis-Unsaturated Esters Mediated by (η²-Propene)TiX₂ (X = Cl or O-i-Pr). A Facile Construction of Bicyclo[3.3.0]octane, -[4.3.0]nonane, and -[3.1.0]hexane Skeletons

Intramolecular Cyclization of 2,7- or 2,8-Bis-unsaturated Esters Mediated by (η²-Propene)Ti(O-i-Pr)₂. Facile Construction of Mono- and Bicyclic Skeletons with Stereoselective Introduction of a Side Chain. A Synthesis of d-Sabinene

Intramolecular Cyclization of 2,7- or 2,8-Bis-unsaturated Esters Mediated by (η²-Propene)Ti(O-i-Pr)₂. Facile Construction of Mono- and Bicyclic Skeletons with Stereoselective Introduction of a Side Chain. A Synthesis of d-Sabinene