Stereoselective titanium-mediated syn -aldol reaction from a lactate-derived chiral ethyl ketone

Solsona, Joan G.; Romea, Pedro; Urpı́, Fèlix

doi:10.1016/j.tetlet.2004.05.077

Cited by 25 publications

(11 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increased selectivity and decreased yield were observed when using 2 equiv of TiCl 4 (condition B) [38]. However, an inversion in the selectivity was observed with only 1 equiv of TiCl 4 (condition C), which yielded aldol adduct 79 with a moderate 1,2-syn/1,4-syn selectivity [39].…”

Section: 4-asymmetric Induction Using α-Alkoxy Ketonesmentioning

confidence: 97%

“…This compound corresponds to the C5-C17 fragment in (+)-dolastatin 19 (38). For this reaction, it was imperative to use a chiral borane, which provided complete stereocontrol.…”

Section: 4-asymmetric Induction Using α-Alkyl Ketonesmentioning

confidence: 99%

“…In these cases, it was possible to obtain good selectivities for the 1,3-anti aldol adduct (Scheme 5.40). 38 Aldol reaction in the total synthesis of apoptolidinone C (226). The Mukaiyama aldol reaction between the enolsilane 231a and β-ester aldehyde 232 formed the aldol adduct 233 with very good selectivity (dr = 90 : 10).…”

Section: 3-asymmetric Induction Using Chiral Aldehydesmentioning

confidence: 99%

See 2 more Smart Citations

Asymmetric Induction in Aldol Additions

Dias¹,

Polo²,

Lucca³

et al. 2013

Modern Methods in Stereoselective Aldol Reactions

View full text Add to dashboard Cite

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].

show abstract

Section: 4-asymmetric Induction Using α-Alkoxy Ketonesmentioning

confidence: 97%

“…This compound corresponds to the C5-C17 fragment in (+)-dolastatin 19 (38). For this reaction, it was imperative to use a chiral borane, which provided complete stereocontrol.…”

Section: 4-asymmetric Induction Using α-Alkyl Ketonesmentioning

confidence: 99%

Section: 3-asymmetric Induction Using Chiral Aldehydesmentioning

confidence: 99%

See 1 more Smart Citation

Asymmetric Induction in Aldol Additions

Dias¹,

Polo²,

Lucca³

et al. 2013

Modern Methods in Stereoselective Aldol Reactions

View full text Add to dashboard Cite

show abstract

“…53 Meanwhile, the desired 1,3-anti-3,4-syn aldol adducts 94 were obtained by using TiCl 3 (i-PrO) or two equivalents of TiCl 4 . [53][54][55] Therefore, the titanium Lewis acid turned out to be crucial for determining the stereochemical outcome of the titanium-mediated aldol reaction from the α-OBn lactate-derived ketone 94 (Scheme 23). The reasons for these results remain unclear.…”

Section: Short Review Syn Thesismentioning

confidence: 99%

Substrate-Controlled Aldol Reactions from Chiral α-Hydroxy Ketones

2016

Self Cite

View full text Add to dashboard Cite

Chiral α-hydroxy ketones are valuable platforms from which highly stereoselective substrate-controlled aldol reactions may be performed. The suitable choice of the hydroxyl protecting group and the enolization conditions produce aldol adducts that can be easily manipulated to give a variety of enantiomerically pure compounds. Moreover, such aldol reactions often play a crucial role in the coupling of elaborate fragments in advanced steps of the synthesis of natural products. Together, these features confer to the α-hydroxy ketones a prominent position among the chiral substrates that are capable of providing highly asymmetric transformations. 1 Introduction 2 Pioneering Contributions 3 Boron-Mediated Aldol Reactions from α-Hydroxy Ethyl Ketones 4 Titanium-Mediated Aldol Reactions from α-Hydroxy Ethyl Ketones 5 Other Aldol Reactions from α-Hydroxy Ethyl Ketones 6 Aldol Reactions from α-Hydroxy Methyl Ketones 7 Conclusions

show abstract

“…The synthesis of the C1–C9 fragment ( 2 ) began with the titanium-mediated aldol addition of the lactate-derived ethyl ketone 6 to 3-butenal (Scheme ). As expected, it afforded the aldol product 10 (dr ≥97:3 by 1 H NMR) in 84% yield, which was converted stereoselectively (dr 94:6, 96%) to diol 6 through an internal-hydride delivery using (Me 4 N)HB(OAc) 3 .…”

mentioning

confidence: 99%

Total Synthesis of (+)-Herboxidiene from Two Chiral Lactate-Derived Ketones

et al. 2011

Self Cite

View full text Add to dashboard Cite

A substrate-controlled synthesis of (+)-herboxidiene from two lactate-derived chiral ketones is described. Remarkably, most of the carbon backbone was constructed through highly stereoselective titanium-mediated aldol reactions and an Ireland-Claisen rearrangement. Furthermore, an oxa-Michael cyclization and a high-yield Suzuki coupling were used to assemble the pyran ring and the diene moiety respectively.

show abstract

Stereoselective titanium-mediated syn -aldol reaction from a lactate-derived chiral ethyl ketone

Cited by 25 publications

References 21 publications

Asymmetric Induction in Aldol Additions

Asymmetric Induction in Aldol Additions

Substrate-Controlled Aldol Reactions from Chiral α-Hydroxy Ketones

Total Synthesis of (+)-Herboxidiene from Two Chiral Lactate-Derived Ketones

Contact Info

Product

Resources

About