Toward the Total Synthesis of the Brasilinolides: Construction of a Differentially Protected C20−C38 Segment

Paterson, Ian; Burton, Paul M.; Cordier, C.; Housden, Michael P.; Mühlthau, Friedrich; Loiseleur, Olivier

doi:10.1021/ol802769e

Cited by 16 publications

(10 citation statements)

References 20 publications

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“…Paterson and coworkers employed aldol reactions involving α-methyl ethyl ketones in the synthesis of several structurally complex natural products, such as (+)-discodermolide [6], (−)-spirangien A [7], (−)-callipeltoside A [8], (+)-phorbaside A [9], and siphonarin B and dihydrosiphonarin B [10] as well as fragments of natural products, such as brasilinolides [11], chivosazoles [12], and reidispongiolide A [13]. In these works, the authors used the boron enolates of α-methyl ethyl ketones containing a β-OPMB, β-OBn, or β-ODMB to form the 1,2-anti/1,4-syn aldol adducts with excellent selectivity.…”

Section: 4-asymmetric Induction Using α-Alkyl Ketonesmentioning

confidence: 99%

“…In the synthesis of (−)-spirangien A (14) (Scheme 5.3), an aldol reaction between the boron E-enolate generated from ethyl ketone (11) and methacrolein (12) forms the 1,2-anti/1,4-syn aldol adduct 13 in high yield with excellent diastereoselectivity; this common precursor corresponds to fragments C13-C19 and C23-C29 in (−)-spirangien A (14) [7]. This reaction occurs through a boatlike transition state, TS5, which contains a hydrogen bond between the β-oxygen of the enolate and the formyl hydrogen of the complexed aldehyde.…”

Section: 4-asymmetric Induction Using α-Alkyl Ketonesmentioning

confidence: 99%

“…The authors used different titanium reagents and evaluated the selectivity of the aldol reactions between ethyl ketones ent- 15,11, and 20 and isobutyraldehyde (2). The best results were obtained for ethyl ketone ent-15 (R = Bn) using Ti(iPrO)Cl 3 as the Lewis acid (Table 5.1, entry 3) [19].…”

Section: 4-asymmetric Induction Using α-Alkyl Ketonesmentioning

confidence: 99%

“…11 Aldol reactions using chiral α-alkoxy aldehydes. a All reactions were conducted at −78 • C in CH 2 Cl 2 except when M = Li (−78 • C in THF).…”

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confidence: 99%

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Asymmetric Induction in Aldol Additions

Dias¹,

Polo²,

Lucca³

et al. 2013

Modern Methods in Stereoselective Aldol Reactions

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The selectivity of aldol reactions involving kinetic enolates is related to various factors such as the nature of the Lewis acid (Li, Mg, B, Al, Ti, Sn, etc.), the presence of stereogenic centers in both the substrates and reagents, the nature of their substituents and the reaction conditions. Another factor of major importance is the nature of the enolate double bond (Z or E) [1].In general, it is well known that in aldol reactions involving metal enolates, which proceed through a six-membered cyclic transition state, the Z-enolate leads to the formation of 1,2-syn aldol adducts and the E-enolate affords aldol adducts with the 1,2-anti configuration. A rationalization for the observed selectivities of these aldol reactions was proposed by Zimmerman and Traxler (Scheme 5.1) [2]. According to this model, the nature of the double bond geometry plays a primary role in determining the energies of the competing transition states. For Z-enolates, the transition state TS2 is more destabilized than transition state TS1 because of the 1,3-diaxial interactions between the R 1 and R 3 substituents as well as between these substituents and one of the metal ligands (L). Therefore, the Z-enolate preferentially leads to the formation of the 1,2-syn aldol adduct.For the E-enolate, 1,3-diaxial interactions between the R 1 and R 3 substituents and between both R 1 and R 3 and one of the metal ligands are present in transition state TS4. Therefore, the 1,2-anti aldol adduct is obtained from the lower energy transition state TS3.Modern aldol reactions use preformed enolates to obtain good yields by preventing side reactions. This methodology has proven to be very effective for various Lewis acids derived from lithium, titanium, tin, and boron. By using preformed enolates with chiral substrates and reagents, it is possible to obtain aldol adducts with an excellent degree of asymmetric induction.The IUPAC defines asymmetric induction as the traditional term describing the preferential formation in a chemical reaction of one enantiomer (or diastereomer) over the other as a result of a chiral feature present in the substrate, reagent, catalyst, or the environment [3].

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Section: 4-asymmetric Induction Using α-Alkyl Ketonesmentioning

confidence: 99%

Section: 4-asymmetric Induction Using α-Alkyl Ketonesmentioning

confidence: 99%

Section: 4-asymmetric Induction Using α-Alkyl Ketonesmentioning

confidence: 99%

“…11 Aldol reactions using chiral α-alkoxy aldehydes. a All reactions were conducted at −78 • C in CH 2 Cl 2 except when M = Li (−78 • C in THF).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Asymmetric Induction in Aldol Additions

Dias¹,

Polo²,

Lucca³

et al. 2013

Modern Methods in Stereoselective Aldol Reactions

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“…Paterson's synthesis of the differentially protected C20-C38 fragment of Brasilinolides is an example of this concept [32]. After the C20-C38 chain was assembled by means of a Ba(OH) 2 mediated HWE between 14a and 14b, the resulting enone 14c was submitted to asymmetric reduction followed by Sharpless epoxidation, leading to the intrincate anti hydroxy-oxirane arrangement present in the natural product (Scheme 14).…”

Section: Synthesis Of Building Blocksmentioning

confidence: 99%

Recent Applications of the Horner-Wadsworth-Emmons Reaction to the Synthesis of Natural Products

Bisceglia¹,

Orelli

2012

COC

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The Horner-Wadsworth-Emmons reaction has evolved in the last years as one of the most powerful and reliable method for stereocontrolled olefin synthesis. The reaction has become a widespread standard tool in natural products total syntheses, providing access to relatively simple as well as highly complex synthetic targets. In this work we present the most representative applications within the field of natural product synthesis from 2000 to the present year. The examples comprise the synthesis of macrocycles, 5 to 7 membered rings, lipids and related compounds, alkaloids and cyclic ethers. They were chosen from a large amount of literature reports and illustrate the use of the HWE reaction in the synthesis and elaboration of key intermediates and in the crucial assembly of highly functionalized synthetic precursors.

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Polypropionate Synthesis via Substrate‐Controlled Stereoselective Aldol Couplings of Chiral Fragments

Ward

2013

Modern Methods in Stereoselective Aldol Reactions

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Toward the Total Synthesis of the Brasilinolides: Construction of a Differentially Protected C20−C38 Segment

Cited by 16 publications

References 20 publications

Asymmetric Induction in Aldol Additions

Asymmetric Induction in Aldol Additions

Recent Applications of the Horner-Wadsworth-Emmons Reaction to the Synthesis of Natural Products

Polypropionate Synthesis via Substrate‐Controlled Stereoselective Aldol Couplings of Chiral Fragments

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