“…Since entries 1−9 in Table provided indication that chelated transition states were not operational, the three α-methylthio aldehydes were examined only under aqueous conditions (entries 10−12). The two diastereomeric products were distinguished by direct comparison of specific 1 H NMR chemical shifts with reported values where available as in the case of 13 and 14 , , by conversion to epoxides as shown for 15 and 16 for analysis of the oxirane coupling constants as in 17 and 18 (cis > trans), or by determination of vicinal coupling constants , in the hydroxy sulfides where possible as in 19 and 20 . …”
The stereochemistry of the indium-promoted reaction of allyl bromide with alpha-thia (PhS and MeS), disubstituted alpha-amino (Bn(2)N, Me(2)N, isoindolyl), and protected alpha-amino aldehydes (Ac and Boc) in water has been evaluated. The reactions involving the sulfur derivatives are minimally diastereoselective, indicating that the allylindium reagent is not thiophilic. Chelation is not observed and pi-facial discrimination is achieved via Felkin-Ahn transition states under the steric control of the substituents. The Garner aldehyde is also anti-diastereoselective. Interestingly, N-acetylmannosamine is appreciably responsive to chelation control and is capable of generating 90% of the syn beta-amino alcohol when reacted in a 0.5 M NH(4)Cl solution. While the alpha-dibenzylamino substituent is too bulky to enter into complexation, the alpha-dimethylamino group is not and can lead to high levels (99%) of syn diastereomer. The size of other neighboring substituents does have an impact on pi-facial discrimination in these systems and can erode the stereoselectivity accordingly.
“…Since entries 1−9 in Table provided indication that chelated transition states were not operational, the three α-methylthio aldehydes were examined only under aqueous conditions (entries 10−12). The two diastereomeric products were distinguished by direct comparison of specific 1 H NMR chemical shifts with reported values where available as in the case of 13 and 14 , , by conversion to epoxides as shown for 15 and 16 for analysis of the oxirane coupling constants as in 17 and 18 (cis > trans), or by determination of vicinal coupling constants , in the hydroxy sulfides where possible as in 19 and 20 . …”
The stereochemistry of the indium-promoted reaction of allyl bromide with alpha-thia (PhS and MeS), disubstituted alpha-amino (Bn(2)N, Me(2)N, isoindolyl), and protected alpha-amino aldehydes (Ac and Boc) in water has been evaluated. The reactions involving the sulfur derivatives are minimally diastereoselective, indicating that the allylindium reagent is not thiophilic. Chelation is not observed and pi-facial discrimination is achieved via Felkin-Ahn transition states under the steric control of the substituents. The Garner aldehyde is also anti-diastereoselective. Interestingly, N-acetylmannosamine is appreciably responsive to chelation control and is capable of generating 90% of the syn beta-amino alcohol when reacted in a 0.5 M NH(4)Cl solution. While the alpha-dibenzylamino substituent is too bulky to enter into complexation, the alpha-dimethylamino group is not and can lead to high levels (99%) of syn diastereomer. The size of other neighboring substituents does have an impact on pi-facial discrimination in these systems and can erode the stereoselectivity accordingly.
“…Not only was excellent regioselectivity observed but good stereocontrol was also exhibited when coupling aldehydes with α-chloropropargyl sulfide using indium metal as the promoter. Again, the two diastereomeric products were distinguished either by direct determination of vicinal coupling constants in the hydroxy sulfides where possible or by conversion to the corresponding epoxides (Figure ) . As noted by entries 2 , 6 , 18 , and 26 (Table ), superior anti ratios were obtained in solvent mixtures containing equal amounts of water and DMF.…”
Section: Resultsmentioning
confidence: 99%
“…The next phase of our study focused on determining whether the chlorosulfide compounds could form products exhibiting stereocontrol. Diastereomeric products were distinguished either by direct determination of vicinal coupling constants in the hydroxy sulfides where possible or by conversion to epoxide compounds (Figure ) 1 Representative J values for hydroxy sulfides and epoxides. …”
Coupling reactions between alpha-chloropropargyl phenyl sulfide (11) and a series of aldehydes under aqueous conditions are reported. Not only is good stereoselectivity observed between syn and anti isomeric products, but excellent regioselectivity is also witnessed. In reactions using indium metal as a promoter, the propargyl functionality (12) is retained, unlike the use of more traditional metals that result in formation of products containing a mixture of both propargyl (12) and allene (13) moieties. The reaction is postulated to proceed via either a chelated or nonchelated route, controlled by the presence or absence of indium (III) chloride, and may be used to create synthetically useful building blocks. The formation of epoxyalkyne (14) molecules, which are found in many natural products and have wide use as synthetic templates, is presented as one example.
“…Seeking to explore the synthetic utility of these products, we developed a two-step local desymmetrization that takes advantage of the diastereotopic ester groups (Scheme 3). 9 Beginning with enantioenriched thioether 3a , reduction of the ketone with sodium borohydride 10 provided the syn -hydroxy sulfide 4a in >20:1 dr and 89% yield. Subsequent acid- promoted cyclization provided lactone 5a in >20:1 dr and 70% yield.…”
An asymmetric sulfa-Michael addition of alkyl thiols to enone diesters is reported. The reaction is catalyzed by a bifunctional triaryliminophosphorane-thiourea organocatalyst and provides a range of α-sulfaketones in high yields and enantioselectivities. Leveraging the gem-diester functional handle via a subsequent diastereotopic group discrimination generates functionalized lactones with three contiguous stereocenters.
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