Diastereoselective Additions of Nucleophiles to α-Acetoxy Ethers Using the α-(Trimethylsilyl)benzyl Auxiliary

Rychnovsky, Scott D.; Cossrow, Jennifer

doi:10.1021/ol0347904

Cited by 18 publications

(14 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reductive allylation could also be conducted in high yield with the isolated and sterically hindered O -(α-acetoxyalkyl)hydroxylamines 2g (Table , entry 3). A silyl enol ether also proved to be a satisfactory nucleophile (Table , entry 4) for capture of the intermediate aminoxocarbenium ion (Table , entry 4) as observed previously with glycosyl and simple acyclic oxocarbenium ions derived from the corresponding acetates . Finally, 2-methylfuran was also found to be a suitable nucleophile enabling the synthesis of the complex hydroxylamines 7e and 7f in moderate yield (Table , entries 5 and 6).…”

mentioning

confidence: 99%

Synthesis of N,N,O-Trisubstituted Hydroxylamines by Stepwise Reduction and Substitution of O-Acyl N,N-Disubstituted Hydroxylamines

Dhanju

Crich

2016

Org. Lett.

View full text Add to dashboard Cite

Diverse N,N,O-trisubstituted hydroxylamines, an under-represented group in compound collections, are readily prepared by partial reduction of N-acyloxy secondary amines with diisobutylaluminum hydride followed by acetylation and reduction of the so-formed O-acyl-N,N-disubstituted hydroxylamines with triethylsilane and boron trifluoride etherate. Use of carbon nucleophiles in the last step, including allyltributylstannane, silyl enol ethers, and 2-methylfuran, gives N,N,O-trisubstituted hydroxylamines with branching α- to the O-substituent. N,N-Disubstiuted hydroxylamines are conveniently prepared by reaction of secondary amines with dibenzoyl peroxide followed by diisobutylaluminum hydride reduction.

show abstract

mentioning

confidence: 99%

Synthesis of N,N,O-Trisubstituted Hydroxylamines by Stepwise Reduction and Substitution of O-Acyl N,N-Disubstituted Hydroxylamines

Dhanju

Crich

2016

Org. Lett.

View full text Add to dashboard Cite

show abstract

“…Entry 6 was generously supplied by Pfizer, Inc., through Dr. Ryan Patman of Pfizer La Jolla . Entry 7 was synthesized by Dr. Jennifer Cossrow in the Rychnovsky group . Entry 8 was synthesized by Dr. Matthew Perry in the Rychnovsky group .…”

Section: Methodsmentioning

confidence: 99%

“…22 Entry 7 was synthesized by Dr. Jennifer Cossrow in the Rychnovsky group. 33 Entry 8 was synthesized by Dr. Matthew Perry in the Rychnovsky group. 34 In Table 4, entries 1−8 were generously supplied by the Morken group.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Nanomole-Scale Assignment and One-Use Kits for Determining the Absolute Configuration of Secondary Alcohols

et al. 2016

Self Cite

View full text Add to dashboard Cite

Two different protocols were developed and optimized to address the need for (1) high sensitivity or (2) convenient utilization in the determination of the absolute configuration of secondary alcohols. The first protocol uses the competing enantioselective conversion (CEC) method to determine configuration on nanomole scale. Reactions were conducted with 145 nmol of the substrate using a 50 μL microsyringe as the reaction vessel, and the absolute configuration was assigned via qualitative determination of the fast reaction by thin-layer chromatography. This protocol resulted in a 50-fold reduction in material required from previous CEC method studies. The approach was evaluated with benzylic and β-aryl systems. The second protocol was optimized to address the needs of practicing medicinal chemists. A one-use CEC kit was developed, where the fast reaction was identified by (1)H NMR spectroscopy and thin-layer chromatography. The CEC reaction conditions developed for the microsyringe protocol and the one-use kit both displayed data consistent with pseudo-first-order kinetics in substrate. Therefore, the lower limit of sensitivity for the substrate is limited only by the ability to effectively detect the reaction conversions between alcohol substrate and ester product.

show abstract

“…Numerous nucleophiles have been found to add efficiently to oxocarbenium ions derived from acylated acetals (Scheme ); they include allylsilanes and allylstannanes,14 thiols,11,15 cyanides,16 hydrides,12a acetylides,11 selenides,17 silyl enol ethers,16 and dialkylzinc 16…”

Section: Reactivity Towards Electrophilesmentioning

confidence: 99%

Aluminum Acetals in Organic Synthesis

et al. 2013

View full text Add to dashboard Cite

Aluminum acetals are easily obtained from esters and lactones by reduction with aluminum hydrides. These thermally unstable tetrahedral intermediates have found applications in organic synthesis, with various methodologies taking advantage both of the stabilities of these aluminum species at low temperatures and of their tendencies to undergo rearrangement into the corresponding aldehydes. Efficient one‐pot transformations can be achieved from aluminum acetals under ionic and radical conditions. A comprehensive overview of the reactivity of these species, including the most recent advances in this field, is presented in this microreview.

show abstract

Diastereoselective Additions of Nucleophiles to α-Acetoxy Ethers Using the α-(Trimethylsilyl)benzyl Auxiliary

Cited by 18 publications

References 24 publications

Synthesis of N,N,O-Trisubstituted Hydroxylamines by Stepwise Reduction and Substitution of O-Acyl N,N-Disubstituted Hydroxylamines

Synthesis of N,N,O-Trisubstituted Hydroxylamines by Stepwise Reduction and Substitution of O-Acyl N,N-Disubstituted Hydroxylamines

Nanomole-Scale Assignment and One-Use Kits for Determining the Absolute Configuration of Secondary Alcohols

Aluminum Acetals in Organic Synthesis

Contact Info

Product

Resources

About