Stereoselective Total Synthesis of (−)‐Borrelidin

Vong, B. G.; Kim, Sun Hee; Abraham, Sunny; Theodorakis, Emmanuel A.

doi:10.1002/ange.200460203

Cited by 24 publications

(6 citation statements)

References 55 publications

(4 reference statements)

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“…=+5.4, c =0.5 in CH 2 Cl 2 ); 1 H NMR (499.873 MHz, CDCl 3 ): δ =0.83 (d, 3 J =6.5 Hz, 3 H; CH 3 ), 0.84 (d, 3 J =6.6 Hz, 3 H; CH 3 ), 0.90 (d, 3 J =6.8 Hz, 3 H; CH 3 ), 1.04 (d, 3 J =6.9 Hz, 3 H; 2‐CH‐C H 3 ), 0.90–1.00 (m, 1 H), 1.19–1.33 (m, 4 H), 1.36–1.43 (m, 1 H), 1.50–1.65 (m, 2 H), 1.78–1.85 (m, 1 H), 2.35–2.44 (m, 1 H; 2‐CH), 3.16 (dd, 2 J =8.9, 3 J =6.9 Hz, 1 H; 9‐CH 2 ), 3.29 (dd, 2 J =9.1, 3 J =5.2 Hz, 1 H; 9‐CH 2 ), 3.78 (s, 3 H; O‐CH 3 ), 4.38 (d, 2 J =11.7 Hz, 1 H; C H 2 ‐Ar), 4.42 (d, 2 J =11.7 Hz, 1 H; C H 2 ‐Ar), 6.85 (m, 2 H; 3′‐CH), 7.23 (m, 2 H; 2′‐CH), 9.59 (d, 3 J =1.9 Hz, 1 H; ‐C(O)H); 13 C NMR (125.709 MHz, CDCl 3 ): δ =13.1 (CH 3 ), 18.3 (CH 3 ), 20.0 (CH 3 ), 20.7 (CH 3 ), 27.4, 27.5, 30.9, 37.0, 41.7, 44.2, 45.5, 55.3 (O‐CH 3 ), 72.7 ( C H 2 ‐Ar), 75.6 (C‐9), 113.7 (2×C‐3′), 129.0 (2×C‐2′), 130.9 (C‐1′), 159.0 (C‐4′), 205.3 (C‐1). The analytical data correspond to those reported previously 22c…”

Section: Methodssupporting

confidence: 89%

“…These results render this macrolide an attractive synthetic target for the development of novel antiangiogenetic drugs. Very recently, four elegant total syntheses have been reported22 among which the synthesis of Theodorakis22c became of particular interest to us. Thus, in his synthesis the key building block for the northern hemisphere of borrelidin, aldehyde (+)‐ 27 , which is a tetradeoxypropionate derivative, was prepared employing the iterative enolate alkylation strategy developed by Myers et al3 in 13 steps starting from iodide 29 in 36 % overall yield 22c…”

Section: Resultsmentioning

confidence: 99%

“…Transformation of (−)‐ 25 to the corresponding Grignard reagent and subjection to the conditions of the directed allylic substitution with ( S )‐(−)‐ 8 gave the tetradeoxypropionate (+)‐ 26 in excellent yield and stereoselectivity (Scheme ). Ozonolysis followed by reductive workup with triphenylphosphine furnished the known aldehyde (+)‐ 27 ,22c thus representing a formal total synthesis of borrelidin. Our synthesis required eight steps from bromide 10 in a global yield of 41 % and thus compares favorably with the approach towards (+)‐ 27 reported by Theodorakis.…”

Section: Resultsmentioning

confidence: 99%

“…Flash chromatography (petroleum ether/ tert ‐butyl methyl ether 100:1) yielded the aldehyde (+)‐ 27 (59.6 mg, 0.178 mmol, 89 %) as a colorless oil. [ α ]${{{20\hfill \atop {\rm D}\hfill}}}$ =+5.0 ( c =1.09 in CH 2 Cl 2 , lit 22c…”

Section: Methodsmentioning

confidence: 99%

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Iterative Deoxypropionate Synthesis Based on a Copper‐Mediated Directed Allylic Substitution: Formal Total Synthesis of Borrelidin (C3–C11 Fragment)

Herber

Breit

2006

Chemistry A European J

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A new iterative strategy for the flexible preparation of any oligodeoxypropionate stereoisomer is presented which relies on an o-DPPB-directed copper mediated allylic substitution employing enantiomerically pure Grignard reagents; the reaction is working with perfect control over all aspects of the reaction selectivity. This key C--C bond-forming step features reversed polarity compared with established enolate alkylation methodology. It thus avoids existing problems of enolate alkylation strategies such as enolate reactivity as well as costs and problems associated with the chiral auxiliary. Practicability of this new method is demonstrated through application in natural product syntheses. Thus, an efficient synthesis of the northern part of the angiogenesis inhibitor borrelidin (28), the deoxypropionate building block 27, could be devised, representing a formal total synthesis.

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Section: Methodssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Iterative Deoxypropionate Synthesis Based on a Copper‐Mediated Directed Allylic Substitution: Formal Total Synthesis of Borrelidin (C3–C11 Fragment)

Herber

Breit

2006

Chemistry A European J

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“…This nucleophilic attack will follow the Bürgi-Dunitz trajectory [63] and result in TS26, which minimizes steric interactions with the R M -group and leads to the Felkin product (Scheme 5.22). Theodorakis and coworkers nicely demonstrated the Felkin induction during their synthesis of (−)-borrelidin (141) involving the late-stage Mukaiyama aldol reaction between the silyl ketene acetal 139a and aldehyde 138, which produced the desired ester 140 in 95% yield with dr = 4 : 1 (Scheme 5.23) [64].…”

Section: 2-asymmetric Induction Using Chiral Aldehydesmentioning

confidence: 99%

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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Entfernbare dirigierende Gruppen in der organischen Synthese und Katalyse

2011

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Dirigierende Gruppen haben in den vergangenen Jahren breite Anwendung gefunden, um Reaktionsselektivitäten in einem breiten Spektrum an übergangsmetallkatalysierten Reaktionen und Reaktionen metallorganischer Reagentien zu steuern. In Fällen, in denen die im Substrat vorhandenen funktionellen Gruppen nicht geeignet sind, um eine effiziente intramolekulare Reagens‐ oder Katalysator‐Steuerung zu ermöglichen, kann das gezielte Einbringen von maßgeschneiderten und wieder entfernbaren reagensdirigierenden Gruppen eine Lösung für dieses Problem bieten. In diesem Aufsatz geben wir eine Überblick zum Stand der Forschung auf diesem Gebiet und schließen dabei sowohl den stöchiometrischen wie den katalytischen Einsatz dirigierender Gruppen ein.

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Stereoselective Total Synthesis of (−)‐Borrelidin

Cited by 24 publications

References 55 publications

Iterative Deoxypropionate Synthesis Based on a Copper‐Mediated Directed Allylic Substitution: Formal Total Synthesis of Borrelidin (C3–C11 Fragment)

Iterative Deoxypropionate Synthesis Based on a Copper‐Mediated Directed Allylic Substitution: Formal Total Synthesis of Borrelidin (C3–C11 Fragment)

Asymmetric Induction in Aldol Additions

Entfernbare dirigierende Gruppen in der organischen Synthese und Katalyse

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