Synthesis of (±)-hotrienol and (±)-santolina alcohol via cyclopropenes

Moiseenkov, A. M.; Czeskis, Boris A.; Semenovsky, A. V.

doi:10.1039/c39820000109

Cited by 15 publications

(5 citation statements)

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“…The EAS shown in eq 1 delivers natural product santolina alcohol 31 in 65% yield (some loss due to product volatility), complete S N 2′ selectivity, and 96:4 er. The catalytic process involves alkyl-substituted substrate 39 , which contains a hydroxyl-substituted quaternary carbon center immediately next to the reactive site.…”

Section: Resultsmentioning

confidence: 99%

A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis

2014

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A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0–5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl–(pinacolatoboron) [alkenyl–B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2′:SN2, and 99:1 enantiomeric ratio (er). NHC–Cu-catalyzed EAS with alkenyl–B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E.

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Section: Resultsmentioning

confidence: 99%

A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis

2014

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“…Nonetheless, the syn-diastereoselectivity was excellent and subsequent efforts from a number of groups showed that the syn selectivity is a general phenomenon for the addition of organometallic reagents to cyclopropenes. Lukina, Rudavshevskaya and Nesmeyanova first demonstrated in 1970 that Grignard reagents add to cyclopropenes (Scheme 8), providing the early groundwork that cyclopropene carbometallations were synthetically useful transformations [53] Continued studies by Nesmeyanova and Rudavshevskaya [54][55][56][57][58][59][60], Levina [61], Moiseenkov [60,62], and Lehmkuhl [63,64], established the generality of Grignard additions to cyclopropenes. Lukina, Rudavshevskaya and Nesmeyanova first demonstrated in 1970 that Grignard reagents add to cyclopropenes (Scheme 8), providing the early groundwork that cyclopropene carbometallations were synthetically useful transformations [53] Continued studies by Nesmeyanova and Rudavshevskaya [54][55][56][57][58][59][60], Levina [61], Moiseenkov [60,62], and Lehmkuhl [63,64], established the generality of Grignard additions to cyclopropenes.…”

Section: Carbometallation Of Cyclopropenesmentioning

confidence: 99%

Metal Mediated and Catalyzed Nucleophilic Additions to Cyclopropenes

Fox¹,

Ni²

2005

COC

151

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This review describes the literature of nucleophilic additions of organometallic and metal hydride reagents to cyclopropenes with a particular focus on the regiochemical and stereochemical aspects of the addition reactions. SCOPE OF THE REVIEWThis review describes the literature of nucleophilic addition reactions of organometallic and metal hydride reagents to cyclopropenes-the simplest examples of which are shown in Equations 1 and 2. The chemistry of cyclopropenes has been the subject of numerous reviews, including excellent treatments by Halton and Banwell [1], Schmidt [2], and Baird [3,4] on the literature prior to 1996 that deals with nucleophilic additions to cyclopropenes. Nakamura has more recently reviewed the chemistry of cyclopropenone acetals [5]-substrates that have been studied extensively in carbometallation reactions. The present review will place emphasis on that literature which has not been covered by the previous reviews. A particular focus is placed on regiochemical and stereochemical aspects of nucleophilic additions to cyclopropenes. For historical context, key contributions to the field will be described (briefly because they have been previously reviewed elsewhere), and to place cyclopropene reactivity into practical context, recent developments in the enantioselective preparation of cyclopropenes will also be described. Current understanding of the mechanism of cyclopropene carbometallation will also be discussed. This review will be limited to description of formal addition reactions as outlined in Eqs 1 and 2, and will not describe cyclopropene hydrogenations, cyclometallations, or addition reactions of heteroatom nucleophiles. CYCLOPROPANES AS TARGETSThe products of nucleophilic additions of cyclopropenes are cyclopropanes, which are attractive targets in their own right because they are structural components of natural products, drug candidates, 3-methanoamino acids, and other biologically relevant materials [6,7]. It is noteworthy that there are more than 1100 hits in the Beilstein database for natural products that contain a cyclopropane with four or

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“…22 The conclusion drawn is that the 1' -2 condensation is stereorandom at C-1 of the electrophilic isoprene unit. Treatment of the ether (130) with reagent (1 3 1) leads to a 1 : 3 mixture of (1 32) and (1 33). 23 Similar reaction of diprenyl ether (1 34) yields lavandulol(l35).…”

Section: Irregular Monoterpenoidsmentioning

confidence: 99%

Monoterpenoids

Grayson¹

1984

Nat. Prod. Rep.

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Synthesis of (±)-hotrienol and (±)-santolina alcohol via cyclopropenes

Cited by 15 publications

References 0 publications

A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis

A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis

Metal Mediated and Catalyzed Nucleophilic Additions to Cyclopropenes

Monoterpenoids

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