21 research outputs found
Grob Fragmentation of 2-Azabicyclo[2.2.2]oct-7-ene: Tool for the Stereoselective Synthesis of Polysubstituted Piperidines
The Grob fragmentation of azabicyclo[2.2.2]octene leads
to a dihydropyridinium
intermediate. This highly reactive species reacts with a variety of
organocuprates and other soft nucleophiles in a regioselective manner,
allowing for the rapid and stereoselective synthesis of 2,3,4-trisubstituted
1,2,3,4-tetrahydropyridines. The resulting products were either reduced
in situ to the corresponding piperidine or used to achieve the stereoselective
construction of various nitrogen heterocycles
Diastereoselective Fluorocyclopropanation of Chiral Allylic Alcohols Using an α‑Fluoroiodomethylzinc Carbenoid
Chiral fluorocyclopropyl
carbinols were synthesized in high diastereoselectivities
via a zinc mediated cyclopropanation reaction, using <i>sec</i>-allylic alcohols as simple building blocks. An enantioselective
version of this transformation was achieved through <i>in situ</i> formation of chiral allylic zinc <i>sec</i>-alkoxides
from the requisite aldehydes using Walsh’s protocol
Diastereoselective Borocyclopropanation of Allylic Ethers Using a Boromethylzinc Carbenoid
A borocyclopropanation of (<i>E</i>)- and (<i>Z</i>)-allylic ethers and styrene
derivatives via the Simmons–Smith
reaction using a novel boromethylzinc carbenoid is described. The
carbenoid precursor is prepared via a 3-step sequence from inexpensive
and commercially available starting materials. This methodology allows
for the preparation of 1,2,3-substituted borocyclopropanes in high
yields and diastereoselectivities. Several postfunctionalization reactions
were also performed to illustrate the versatility of these building
blocks
Diastereoselective Fluorocyclopropanation of Chiral Allylic Alcohols Using an α‑Fluoroiodomethylzinc Carbenoid
Chiral fluorocyclopropyl
carbinols were synthesized in high diastereoselectivities
via a zinc mediated cyclopropanation reaction, using <i>sec</i>-allylic alcohols as simple building blocks. An enantioselective
version of this transformation was achieved through <i>in situ</i> formation of chiral allylic zinc <i>sec</i>-alkoxides
from the requisite aldehydes using Walsh’s protocol
Triflic Anhydride Mediated Synthesis of Imidazo[1,5‑<i>a</i>]azines
Imidazo[1,5-<i>a</i>]azines are synthesized in moderate to excellent yields using a mild cyclodehydration/aromatization reaction triggered by the use of triflic anhydride (Tf<sub>2</sub>O) and 2-methoxypyridine (2-MeOPyr). Various substitution patterns and functional groups were found to be compatible under the optimized conditions. In addition, a 5-bromo-3-aryl derivative was also shown to be active in a Sonogashira cross-coupling and direct arylation reactions. A tertiary amide was compatible as a substrate leading to the synthesis of an imidazo[1,5-<i>a</i>]pyridinium triflate
C–H Functionalization of Cyclopropanes: A Practical Approach Employing a Picolinamide Auxiliary
A Pd-catalyzed, picolinamide-enabled, and efficient C–H arylation of cyclopropanes is described. The reaction can be promoted by either a silver additive or catalytic pivalic acid in the presence of a carbonate base. Various aryl iodides can be employed as coupling partners, providing exclusively <i>cis</i>-substituted cyclopropylpicolinamides
Access to Cyclopropyl-Fused Azacycles via a Palladium-Catalyzed Direct Alkenylation Strategy
Palladium-catalyzed
direct alkenylation of cyclopropyl C–H
bonds proceeds in high efficiency. This transformation provides access
to novel cyclopropyl-fused azacycles. Ligand studies suggest that
bisphosphine monoxide analogues of dppf and <i>rac</i>-BINAP
are the active ligand species. Preliminary results support that both
BozPhos and IPrMonophos ligands can achieve high enantioinduction
for this novel direct alkenylation reaction. To date, this represents
the first example of enantioselective C–H functionalization
employing a bisphosphine monoxide ligand
Design and Synthesis of Chiral Heteroleptic Rhodium(II) Carboxylate Catalysts: Experimental Investigation of Halogen Bond Rigidification Effects in Asymmetric Cyclopropanation
A general method for the synthesis of chiral heteroleptic
rhodium(II)
tetracarboxylate catalysts is reported. The chlorinated TCPT unit
was found to be an efficient polarity-control group, allowing the
isolation of each complex from a mixture of six possible products.
This approach contributes to enlarging the scope of accessible chiral
Rh(II) catalysts and allowed further study of the halogen bond rigidification
effect observed in chlorinated complexes
Design and Synthesis of Chiral Heteroleptic Rhodium(II) Carboxylate Catalysts: Experimental Investigation of Halogen Bond Rigidification Effects in Asymmetric Cyclopropanation
A general method for the synthesis of chiral heteroleptic
rhodium(II)
tetracarboxylate catalysts is reported. The chlorinated TCPT unit
was found to be an efficient polarity-control group, allowing the
isolation of each complex from a mixture of six possible products.
This approach contributes to enlarging the scope of accessible chiral
Rh(II) catalysts and allowed further study of the halogen bond rigidification
effect observed in chlorinated complexes
Difluorocarbene Addition to Alkenes and Alkynes in Continuous Flow
The first <i>in-flow</i> difluorocarbene generation and
addition to alkenes and alkynes is reported. The application of continuous
flow technology allowed for the controlled generation of difluorocarbene
from TMSCF<sub>3</sub> and a catalytic quantity of NaI. The <i>in situ</i> generated electrophilic carbene reacts smoothly
with a broad range of alkenes and alkynes, allowing the synthesis
of the corresponding difluorocyclopropanes and difluorocyclopropenes.
The reaction is complete within a 10 min residence time at high reaction
concentrations. With a production flow rate of 1 mmol/min, continuous
flow chemistry enables scale up of this process in a green, atom-economic,
and safe manner