Stereoselective titanium-mediated aldol reactions of (S)-2-tert-butyldimethylsilyloxy-3-pentanone

Nebot, Joaquim; Figueras, Sergi; Romea, Pedro; Urpı́, Fèlix; Ji, Yining

doi:10.1016/j.tet.2006.09.034

Cited by 28 publications

(16 citation statements)

References 68 publications

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“…7,15 Taking advantage of these results, the stereochemistry of aldol adducts 9, 10, 12 and 15 from lactate-derived ketones 2e5 was initially assigned as 2,4-syn-4,5-syn and was later confirmed during the application to the synthesis of natural products. In turn, the absolute configuration of aldol adducts from ketones containing bulky R 2 groups, 19ae20a, or different silicon protecting groups, 24ae26a, was confirmed by chemical correlation.…”

Section: Stereochemistry and Mechanismmentioning

confidence: 97%

“…In this context, we reported that the titaniummediated aldol reactions from (S) 2-tert-butyldimethylsilyloxy-3-pentanone give the corresponding synesyn adducts in a highly stereoselective manner. 6,7 However, the influence of structural elements of other a-silyloxy ketones, such as R 1 , R 2 or the protecting silicon group on the stereochemical outcome of related reactions was unclear (Scheme 1). 8,9 Here, we document a comprehensive study of titanium-mediated aldol reactions from chiral a-silyloxy ketones.…”

Section: Introductionmentioning

confidence: 99%

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Highly stereoselective titanium-mediated aldol reactions from chiral α-silyloxy ketones. A reliable tool for the synthesis of natural products

et al. 2011

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Section: Stereochemistry and Mechanismmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Highly stereoselective titanium-mediated aldol reactions from chiral α-silyloxy ketones. A reliable tool for the synthesis of natural products

et al. 2011

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“…In contrast with ketone 77, enolization using either Ti(iPrO)Cl 3 or TiCl 4 led to a 1,2-syn/1,4-syn induction preference for aldol adducts derived from the α-silyloxy protected ketone 81 (Scheme 5.15) [40]. This chemistry was extended to other derivatives, such as the allyl-derivative ketone 82 [41], and both haloderivatives 83 and 84 [42], which obtained high selectivities (dr > 10 : 1).…”

Section: 4-asymmetric Induction Using α-Alkoxy Ketonesmentioning

confidence: 99%

“…5.39Aldol reaction in the synthesis of the C1-C22 fragment of leucascandrolide A 5 40. 1,3-Induction of aldol reactions involving β-ester and β-OTBS aldehydes.…”

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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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“…126 (46), a lactate-derived chiral ketone, undergoes titanium-mediated aldols giving all-syn products in high de. 127 Low-temperature de 1 H and 13 C NMR evidence suggests a likely TS to account for the selectivity. ( A highly anti -selective catalytic aldol reaction of amides with aldehydes has been de reported.…”

Section: Other Stereoselective Aldol Reactionsmentioning

confidence: 99%

Reactions of Aldehydes and Ketones and their Derivatives

Murray

2010

Organic Reaction Mechanisms · 2006

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Stereoselective titanium-mediated aldol reactions of (S)-2-tert-butyldimethylsilyloxy-3-pentanone

Cited by 28 publications

References 68 publications

Highly stereoselective titanium-mediated aldol reactions from chiral α-silyloxy ketones. A reliable tool for the synthesis of natural products

Highly stereoselective titanium-mediated aldol reactions from chiral α-silyloxy ketones. A reliable tool for the synthesis of natural products

Asymmetric Induction in Aldol Additions

Reactions of Aldehydes and Ketones and their Derivatives

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