Hello all!
I have been trying to get an Aldol reaction between a cyclic ketone next to a quat center and acetaldehyde to go but I have had no luck. I’ve tried a bunch of bases like LDA LiHMDS, NaH, KHMDS, and my aldehyde looks pretty dry by nmr although it is not sure sealed. Most of the time I just get starting material back so I must be hydrolyzing the enolate some how.
I am now trying to get a mukaiyama aldol to go ,but do you guys have any advice?
I hope to eliminate the formed beta hydroxy group and get the Enone. I could not find good precedent for the aldol condensation reaction in one step, so I am attempting multi step.
Direct asymmetric aldol reaction of glycinates represents an intriguing and straightforward strategy to make biologically significant chiral β-hydroxy-α-amino acid derivatives. But it is not easy to realize the transformation due to the disruption of the reactive NH2 group of glycinates. Inspired by enzymatic aldol reaction of glycine, we successfully developed asymmetric aldol reaction of glycinate 5 and trifluoromethyl ketones 4 with 0.1-0.0033 mol% of chiral N-methyl pyridoxal 7a as the catalyst, producing chiral β-trifluoromethyl-β-hydroxy-α-amino acid esters 6 in 55-82% yields (for the syn-diastereomers) with up to >20:1 dr and 99% ee under very mild conditions. The reaction proceeds via a catalytic cycle similar to the enzymatic aldol reaction of glycine. Pyridoxal catalyst 7a activates both of the reactants at the same time and brings them together in a specific spatial orientation, accounting for the high efficiency, excellent diastereo- and enantioselectivities.
https://ift.tt/3cMH18r
Appropriate and simultaneous activation of robust and easily to handle [Tol-BINAP]NiCl2 and aromatic aldehydes with TIPSOTf orchestrates a direct, asymmetric, and catalytic aldol reaction of a wide array of N-acyl-1,3-thiazinane-2-thiones. This method enables the corresponding TIPS-protected anti aldol adducts to be obtained in a highly efficient and atom economical manner.
Abstract
A direct and asymmetric aldol reaction of N-acyl thiazinanethiones with aromatic aldehydes catalyzed by chiral nickel(II) complexes is reported. The reaction gives the corresponding O-TIPS-protected anti-aldol adducts in high yields and with remarkable stereocontrol and atom economy. Furthermore, the straightforward removal of the achiral scaffold provides enantiomerically pure intermediates of synthetic interest, which involve precursors for anti-α-amino-β-hydroxy and α,β-dihydroxy carboxylic derivatives. Theoretical calculations explain the observed high stereocontrol.
https://ift.tt/2QB80LU
A copper(I)‐catalyzed asymmetric vinylogous aldol‐type reaction of allylazaarenes is disclosed. It provides an array of chiral γ‐hydroxyl‐α,β‐unsaturated azaarenes in moderate to excellent regio‐, (E)/(Z)‐, and enantioselectivities.
Abstract
A vinylogous aldol‐type reaction of allylazaarenes and aldehydes is disclosed that affords a series of chiral γ‐hydroxyl‐α,β‐unsaturated azaarenes in moderate to excellent yields with high to excellent regio‐ and enantioselectivities. With (R,RP)‐TANIAPHOS and (R,R)‐QUINOXP* as the ligand, the carbon‐carbon double bond in the products is generated in (E)‐form. With (R)‐DTBM‐SEGPHOS as the ligand, (Z)‐form carbon‐carbon double bond is formed in the major product. In this vinylogous reaction, aromatic, α,β‐unsaturated, and aliphatic aldehydes are competent substrates. Moreover, a variety of azaarenes, such as pyrimidine, pyridine, pyrazine, quinoline, quinoxaline, quinazoline, and benzo[d]imidazole are well‐tolerated. At last, the chiral vinylogous product is demonstrated as a suitable Michael acceptor towards CuI‐catalyzed nucleophilic addition with organomagnesium reagents.
https://ift.tt/3pOtNgg
Addition of a carbene catalyst to vinyl carbonates initiates the aldol reaction. This aldol event is subsequently followed by an enantioselective acylation that is mediated by the same (chiral) NHC catalyst without introducing any additional substance. This post‐aldol process takes care of the enantioselectivity issues and drives the otherwise reversible aldol reaction toward a complete conversion.
Abstract
The dominated approaches for asymmetric aldol reactions have primarily focused on the aldol carbon–carbon bond‐forming events. Here we postulate and develop a new catalytic strategy that seeks to modulate the reaction thermodynamics and control the product enantioselectivities via post‐aldol processes. Specifically, an NHC catalyst is used to activate a masked enolate substrate (vinyl carbonate) to promote the aldol reaction in a non‐enantioselective manner. This reversible aldol event is subsequently followed by an enantioselective acylative kinetic resolution that is mediated by the same (chiral) NHC catalyst without introducing any additional substance. This post‐aldol process takes care of the enantioselectivity issues and drives the otherwise reversible aldol reaction toward a complete conversion. The acylated aldol products bearing quaternary/tetrasubstituted carbon stereogenic centers are formed in good yields and high optical purities.
https://ift.tt/2E5Xbf1
Do you think if i used a solvent such as DMSO or THF it would interfere with the reaction. I could just take off the bromine but that wld be a last resort. I tried it before with methylamine dissolved in methanol, and nitroethane. I left them stirring (the aldehyde wouldnt dissolve) for 24 hours and ended up with a yellow powder on the bottom of my container. Dont know if this is the aldehyde or the nitropropene because they're the sale color.
Hello,
my current exam scheduled for march will include aldol reactions and I believe that I may need to know them in general. However, I have trouble identifiying which aldol reacts as a nucleophile.
Is it the one with more electrons (like an ester or a carbonic acid)? Are there completely different factors? As an example, when we let Acetone and Benzaldehyde react, then why does Acetone play as a nucleophile?
EDIT: Additionally, what does determine cis/trans in an aldol condesnsation? Is it the syn anti of the aldol addition proudct?
Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b13156
https://ift.tt/32jadgB
A direct and asymmetric aldol reaction of N ‐acyl thiazinanethiones with aromatic aldehydes catalyzed by chiral nickel(II) complexes is documented. The reaction gives the corresponding O ‐TIPS protected anti aldol adducts in high yields and with a remarkable stereocontrol and atom economy. Furthermore, the straightforward removal of the achiral scaffold provides enantiomerically pure intermediates of synthetic interest, which involve precursors for anti α‐amino‐β‐hydroxy and α,β‐dihydroxy carboxylic derivatives. Theoretical calculations account for the observed high stereocontrol.
https://ift.tt/2QB80LU
A vinylogous aldol‐type reaction of allylazaarenes and aldehydes is disclosed, which affords a series of chiral γ‐hydroxyl‐α,β‐unsaturated azaarenes in moderate to excellent yields with high to excellent regio‐ and enantioselectivities. With ( R , R P )‐TANIAPHOS and ( R , R )‐QUINOXP* as the ligand, the carbon‐carbon double bond in the products is generated in ( E )‐form. With ( R )‐DTBM‐SEGPHOS as the ligand, ( Z )‐form carbon‐carbon double bond is formed in the major product. In this vinylogous reaction, aromatic, α,β‐unsaturated, and aliphatic aldehydes are competent substrates. Moreover, a variety of azaarenes, such as pyrimidine, pyridine, pyrazine, quinoline, quinoxaline, quinazoline, and benzo[ d ]imidazole are well tolerated. At last, the chiral vinylogous product is demonstrated as a suitable Michael acceptor towards CuI‐catalyzed nucleophilic addition with organomagnesium reagents.
https://ift.tt/3pOtNgg
The dominated approaches for asymmetric aldol reactions have primarily focused on the aldol carbon‐carbon bond forming events. Here we postulate and develop a new catalytic strategy that seeks to modulate the reaction thermodynamics and control the product enantioselectivities via post‐aldol processes. Specifically, a NHC catalyst is used to activate a masked enolate substrate (vinyl carbonate) to promote the aldol reaction in a non‐enantioselective manner. This aldol event is subsequently followed by a dynamic kinetic resolution process that is mediated by the same (chiral) NHC catalyst without introducing any additional substance. This post‐aldol process takes care of the enantioselectivity issues and drives the otherwise reversible aldol reaction toward a complete conversion. The acylated aldol products bearing quaternary/tetrasubstituted carbon stereogenic centers are formed in good yields and high optical purities.
https://ift.tt/2E5Xbf1
