18 research outputs found
Electrochemical Vicinal C–H Difunctionalization of Saturated Azaheterocycles
A method to functionalize two vicinal
C–H bonds
of saturated
azaheterocycles is described. The procedure involves subjecting the
substrate to a mixture of hydrochloric acid, acetic acid, and acetic
anhydride in an undivided electrochemical cell at a constant current,
resulting in stereoselective conversion to the corresponding α-acetoxy-β-chloro
derivative. The α-position can be readily substituted with a
range of other groups, including alkyl, aryl, allyl, alkynyl, alkoxy,
or azido functionalities. Furthermore, we demonstrate that the β-chloro
position can be engaged in Suzuki cross-coupling. This protocol thus
enables the rapid diversification of simple five-, six-, and seven-membered
saturated azaheterocycles at two adjacent positions
Higher-Order Cyclopropenimine Superbases: Direct Neutral Brønsted Base Catalyzed Michael Reactions with α‑Aryl Esters
The
synthesis and characterization of six new classes of higher-order
superbases, including five that incorporate cyclopropenimine functionality,
has been achieved. We propose a nomenclature that designates these
as the CG<sub>2</sub>, GC<sub>2</sub>, PC<sub>3</sub>, PC<sub>1</sub>, C<sub>3</sub>, and GP<sub>2</sub> classes of superbases. The p<i>K</i><sub>BH+</sub> values were measured to be between 29.0
and 35.6 in acetonitrile. Linear correlations of ten superbase basicities
vs that of their substituents demonstrated the insulating effect of
the cyclopropenimine core. The molecular structures of several of
these materials were obtained by single-crystal X-ray analysis, revealing
interesting aspects of conformational bias and noncovalent organization.
The types of superbasic cores and substituents were each reliably
shown to affect selectivity for deprotonation over alkylation. Higher-order
cyclopropenimine and guanidine superbase stability to hydrolysis was
found to correlate to basicity. Finally, a GC<sub>2</sub> base was
found to catalyze conjugate additions of α-aryl ester pronucleophiles,
representing the first report of a neutral Brønsted base to catalyze
such reactions
Cyclopropenimine-Catalyzed Enantioselective Mannich Reactions of <i>tert</i>-Butyl Glycinates with <i>N</i>‑Boc-Imines
Cyclopropenimine <b>1</b> is shown to catalyze Mannich reactions between glycine imines
and <i>N</i>-Boc-aldimines with high levels of enantio-
and diastereocontrol. The reactivity of <b>1</b> is shown to
be substantially greater than that of a widely used thiourea cinchona
alkaloid-derived catalyst. A variety of aryl and aliphatic <i>N</i>-Boc-aldimines are effective substrates for this transformation.
A preparative-scale reaction to deliver >90 mmol of product is
shown using 1 mol % catalyst. The products of this transformation
can be converted into several useful derivatives
Cyclopropenone Catalyzed Substitution of Alcohols with Mesylate Ion
The cyclopropenone catalyzed nucleophilic substitution of alcohols by methanesulfonate ion with inversion of configuration is described. This work provides an alternative to the Mitsunobu reaction that avoids the use of azodicarboxylates and generation of hydrazine and phosphine oxide byproducts. This transformation is shown to be compatible with a range of functionality. A cyclopropenone scavenge strategy is demonstrated to aid purification
Higher-Order Cyclopropenimine Superbases: Direct Neutral Brønsted Base Catalyzed Michael Reactions with α‑Aryl Esters
The
synthesis and characterization of six new classes of higher-order
superbases, including five that incorporate cyclopropenimine functionality,
has been achieved. We propose a nomenclature that designates these
as the CG<sub>2</sub>, GC<sub>2</sub>, PC<sub>3</sub>, PC<sub>1</sub>, C<sub>3</sub>, and GP<sub>2</sub> classes of superbases. The p<i>K</i><sub>BH+</sub> values were measured to be between 29.0
and 35.6 in acetonitrile. Linear correlations of ten superbase basicities
vs that of their substituents demonstrated the insulating effect of
the cyclopropenimine core. The molecular structures of several of
these materials were obtained by single-crystal X-ray analysis, revealing
interesting aspects of conformational bias and noncovalent organization.
The types of superbasic cores and substituents were each reliably
shown to affect selectivity for deprotonation over alkylation. Higher-order
cyclopropenimine and guanidine superbase stability to hydrolysis was
found to correlate to basicity. Finally, a GC<sub>2</sub> base was
found to catalyze conjugate additions of α-aryl ester pronucleophiles,
representing the first report of a neutral Brønsted base to catalyze
such reactions
Enantioselective Brønsted Base Catalysis with Chiral Cyclopropenimines
Cyclopropenimines are shown to be a highly effective
new class
of enantioselective Brønsted base catalysts. A chiral 2,3-bisÂ(dialkylamino)Âcyclopropenimine
catalyzes the rapid Michael reaction of a glycine imine substrate
with high levels of enantioselectivity. A preparative scale reaction
to deliver 25 g of product is demonstrated, and a trivial large scale
synthesis of the optimal catalyst is shown. In addition, the basicity
of a 2,3-bisÂ(dialkylamino)Âcyclopropenimine is measured for the first
time and shown to be approximately equivalent to the P<sub>1</sub>-<i>t</i>Bu phosphazene base. An X-ray crystal structure
of the protonated catalyst is shown along with a proposed mechanistic
and stereochemical rationale
Enantioselective Brønsted Base Catalysis with Chiral Cyclopropenimines
Cyclopropenimines are shown to be a highly effective
new class
of enantioselective Brønsted base catalysts. A chiral 2,3-bisÂ(dialkylamino)Âcyclopropenimine
catalyzes the rapid Michael reaction of a glycine imine substrate
with high levels of enantioselectivity. A preparative scale reaction
to deliver 25 g of product is demonstrated, and a trivial large scale
synthesis of the optimal catalyst is shown. In addition, the basicity
of a 2,3-bisÂ(dialkylamino)Âcyclopropenimine is measured for the first
time and shown to be approximately equivalent to the P<sub>1</sub>-<i>t</i>Bu phosphazene base. An X-ray crystal structure
of the protonated catalyst is shown along with a proposed mechanistic
and stereochemical rationale
Organocatalytic Carbonyl-Olefin Metathesis
The development of a catalytic carbonyl-olefin metathesis
strategy
is reported, in the context of the ring-opening metathesis of cyclopropenes
with aldehydes using a simple hydrazine catalyst. The key to this
reaction is a conceptual blueprint for metathesis chemistry that forgoes
the traditional reliance on [2 + 2] cycloaddition modes in favor of
a [3 + 2] paradigm
Organocatalytic Carbonyl-Olefin Metathesis
The development of a catalytic carbonyl-olefin metathesis
strategy
is reported, in the context of the ring-opening metathesis of cyclopropenes
with aldehydes using a simple hydrazine catalyst. The key to this
reaction is a conceptual blueprint for metathesis chemistry that forgoes
the traditional reliance on [2 + 2] cycloaddition modes in favor of
a [3 + 2] paradigm
Methods for the Synthesis of Functionalized Pentacarboxycyclopentadienes
Protocols for the
synthesis of diverse pentacarboxycyclopentadienes
are described. Starting from readily available pentacarbomethoxycyclopentadiene,
transesterification offers single-step access to aliphatic ester derivatives,
while treatment with amines produces mono- or diamides. For less nucleophilic
alcohols, an alternative procedure involving the in situ generation
and esterification of a putative cyclopentadiene pentaacid chloride
has been developed