The traceless Petasis borono‐Mannich reaction of enals, sulfonylhydrazines, and allylboronates, catalyzed by chiral biphenols, results in an asymmetric reductive transposition of the in situ generated allylic diazene. Acyclic 1,4‐diene products bearing either alkyl‐ or aryl‐substituted benzylic stereocenters are afforded in excellent yields and enantiomeric ratios of up to 99:1. The use of crotylboronates in the reaction results in concomitant formation of two stereocenters in either a 1,4‐
The traceless Petasis borono‐Mannich reaction of enals, sulfonylhydrazines, and allylboronates, catalyzed by chiral biphenols, results in an asymmetric reductive transposition of the in situ generated allylic diazene. Acyclic 1,4‐diene products bearing either alkyl‐ or aryl‐substituted benzylic stereocenters are afforded in excellent yields and enantiomeric ratios of up to 99:1. The use of crotylboronates in the reaction results in concomitant formation of two stereocenters in either a 1,4‐
- NSF-PAR ID:
- 10047636
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 56
- Issue:
- 52
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 16631-16635
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract syn oranti relationship from the correspondingE ‐ orZ ‐crotylboronate used in the reaction. The use of β‐monosubstituted enals in the asymmetric traceless Petasis borono‐Mannich reaction of crotylboronates installs tertiary methyl‐bearing stereocenters in good yields and high enantioselectivities. -
more » « less
Abstract The chemical synthesis of molecules with closely packed atoms having their bond coordination saturated is a challenge to synthetic chemists, especially when three-dimensional control is required. The organocatalyzed asymmetric synthesis of acyclic alkenylated, alkynylated and heteroarylated quaternary carbon stereocenters via 1,4-conjugate addition is here catalyzed by 3,3´-bisperfluorotoluyl-BINOL. The highly useful products (31 examples) are produced in up to 99% yield and 97:3 er using enediketone substrates and potassium trifluoroorganoborate nucleophiles. In addition, mechanistic experiments show that the (
Z )–isomer is the reactive form, ketone rotation at the site of bond formation is needed for enantioselectivity, and quaternary carbon formation is favored over tertiary. Density functional theory-based calculations show that reactivity and selectivity depend on a key n→π* donation by the unbound ketone’s oxygen lone pair to the boronate-coordinated ketone in a 5-exo-trig cyclic ouroboros transition state. Transformations of the conjugate addition products to key quaternary carbon-bearing synthetic building blocks proceed in good yield. -
more » « less
Abstract We describe a copper catalyst that promotes the addition of phosphines to cyclopropenes at ambient temperature. A range of cyclopropylphosphines bearing different steric and electronic properties can now be accessed in high yields and enantioselectivities. Enrichment of phosphorus stereocenters is also demonstrated via a Dynamic Kinetic Asymmetric Transformation (DyKAT) process. A combined experimental and theoretical mechanistic study supports an elementary step featuring insertion of a CuI‐phosphido into a carbon‐carbon double bond. Density functional theory calculations reveal migratory insertion as the rate‐ and stereo‐determining step, followed by a
syn‐ protodemetalation. -
more » « less
Abstract We describe a copper catalyst that promotes the addition of phosphines to cyclopropenes at ambient temperature. A range of cyclopropylphosphines bearing different steric and electronic properties can now be accessed in high yields and enantioselectivities. Enrichment of phosphorus stereocenters is also demonstrated via a Dynamic Kinetic Asymmetric Transformation (DyKAT) process. A combined experimental and theoretical mechanistic study supports an elementary step featuring insertion of a CuI‐phosphido into a carbon‐carbon double bond. Density functional theory calculations reveal migratory insertion as the rate‐ and stereo‐determining step, followed by a
syn‐ protodemetalation. -
more » « less
Abstract The diastereodivergent synthesis of bridged 1,2,3,4‐tetrahydroisoquinoline derivatives has been achieved by using appropriate modularly designed organocatalysts (MDOs) that are self‐assembled in situ from amino acids and cinchona alkaloid derivatives. The domino Mannich/aza‐Michael/aldol reaction between (
E )‐2‐[2‐(3‐aryl‐3‐oxoprop‐1‐en‐1‐yl)phenyl]acetaldehydes and ethyl or benzyl (E )‐2‐[(4‐methoxyphenyl)imino]acetates catalyzed by MDOs gives two different diastereomers of the desired bridged tetrahydroisoquinolines in good yields and excellent diastereoselectivities (up to 99:1 dr) and enantioselectivities (up to >99%ee ). The diastereodivergence was achieved in the aldol reaction step.magnified image
