RESUMO
N-Sulfinyl metalloenamines, derived from geometry-defined ß,ß-disubstituted enesulfinamides, undergo conjugate addition-elimination reaction with ß-tosyl nitroolefin to afford α-sulfonylvinylated ketimines with high stereocontrol. Further desulfonylation using sodium naphthalenide gives carbonyl surrogates bearing a less-accessible acyclic quaternary α-stereocenters substituted with an ethenyl group and two sterically and electronically similar groups (e.g., methyl and ethyl). Synthetic application of the described protocol was demonstrated by enantioselective synthesis of (S)-bakuchiol.
RESUMO
A stereocontrolled protocol was developed to construct less accessible fluorine-containing acyclic tetrasubstituted stereocenters bearing two sterically and electronically similar alkyl groups at the α-position of carbonyls. In this process, tBuOK-promoted stereospecific α-deprotonation of α,α-disubstituted N-tert-butanesulfinyl ketimines or NH deprotonation of ß,ß-disubstituted enesulfinamides generates geometry-defined multisubstituted metalloenamines, followed by stereoselective electrophilic fluorination with the N-fluoro ammonium salt of quinine, affording the acyclic α-fluorinated ketimines with excellent diastereoselectivities.
RESUMO
The metalloenamines, formed by NH-deprotonation of ß,ß-disubstituted enesulfinamides, can undergo reactions with commercially available electrophilic cyanating reagents such as tosyl cyanide (TsCN) or 3-oxo-1,2-benziodoxole-1(3H)-carbonitrile (CBX). Through the utilization of appropriate stereoisomers of enesulfinamides, this method enables the selective synthesis of any of the four stereoisomers of α,α-disubstituted ß-sulfinylimino nitriles, which feature acyclic quaternary stereocenters and are typically more challenging to synthesize. These compounds can then undergo stereoselective nucleophilic addition, leading to the creation of valuable enantioenriched multisubstituted ß-amino carbonyl surrogates with a high degree of structural diversity.
RESUMO
Enamine and iminium ion-mediated asymmetric organocatalysis was not successful in achieving highly stereoselective α-chlorination of acyclic α,α-disubstituted carbonyls. To address this limitation, an alternative method was developed, which involved the use of geometry-defined persubstituted enesulfinamides to intercept the electrophilic chlorinating reagent. This approach enables the asymmetric construction of challenging acyclic α,α-disubstituted α-chlorinated ketimines with a high degree of stereoselectivity. The use of chloramine-T, a cost-effective and stable chlorine source rarely utilized in asymmetric electrophilic chlorination, plays a crucial role in achieving superior stereocontrol.
RESUMO
Current methods for the asymmetric α-sulfenylation of carbonyls cannot be applied to acyclic carbonyls that have two similar substituents at the α-position. This research demonstrated that the electrophilic sulfenylation of geometry-defined acyclic ß,ß-disubstituted enesulfinamides using S-aryl or S-alkyl benzenethiosulfonates can be highly stereoselective. This process results in enantioenriched α,α-disubstituted α-sulfenylated ketone surrogates with sulfur-containing acyclic tetrasubstituted carbon stereocenters bearing two electronically and sterically similar substituents (e.g., methyl and ethyl). Furthermore, by employing the corresponding stereoisomers of enensulfinamides, any of the four stereoisomers of α-sulfenylated ketimines can be selectively accessed.
RESUMO
In the presence of boron trifluoride, conjugate addition of organocuprates to α-substituted α,ß-unsaturated N-tert-butanesulfinyl ketimines provides facile access to acyclic ß,ß-disubstituted enesulfinamides with high ratios of geometric isomers. Diverse and challenging to synthesize, multisubstituted aza-enolates bearing two electronically and sterically similar ß-substituents, which are important precursors for asymmetric construction of the less accessible acyclic quaternary or tetrasubstituted stereocenters at the α-position of ketimines, can be efficiently prepared in good yields with high stereocontrol.
RESUMO
Hydroxymethylation of α-branched N-tert-butanesulfinyl ketimines with formaldehyde equivalents was developed to stereoselectively construct acyclic quaternary stereocenters bearing two sterically and electronically similar substituents. The stereoselective tBuOK-promoted α-deprotonation of acyclic ketimines allowed for the stereodefined formation of fully substituted aza-enolates, followed by facially selective C-C bond formation involving formaldehyde formed in situ, yielding α-hydroxymethylated products with precise stereocontrol.
Assuntos
Carbono , Iminas , Carbono/química , Estereoisomerismo , Iminas/química , FormaldeídoRESUMO
α-Tertiary hydroxyimines were stereoselectively synthesized from enantioenriched N-tert-butanesulfinyl ketimines using potassium tert-butoxide, molecular oxygen, and trimethyl phosphite. The stereoselective hydroxylation of acyclic ketimines bearing two sterically similar α-substituents was achieved by controlling the geometry of the metalloenamine intermediates and the facial selectivity of hydroxylation. The synthetic utility of the resulting α-tertiary hydroxyimines was demonstrated through the successful diastereoselective synthesis of highly substituted ß-amino alcohols.
RESUMO
Vicinal quaternary-tertiary carbon stereocenters were constructed with excellent stereoselectivity via aza-enolization of enantioenriched acyclic N-tert-butanesulfinyl ketimines bearing two sterically similar α-linear alkyl substituents followed by conjugate addition to nitroalkenes. Further changes of the absolute configuration of the sulfinyl group and/or the α-stereocenter in the ketimine allowed the facile stereodivergent synthesis of all four diastereomers of the Michael-type alkylation adducts. This reaction is a successful example of acyclic stereocontrol based on stereoselective α-deprotonation for the formation of fully substituted aza-enolates from ketone derivatives.