Highly Selective Asymmetric
Rh-Catalyzed Hydroformylation
of Heterocyclic Olefins
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Abstract
A small family of new chiral hybrid, diphosphorus ligands,
consisting
of phosphine-phosphoramidites <b>L1</b> and <b>L2</b> and
phosphine-phosphonites <b>L3a–c</b>, was synthesized
for the application in Rh-catalyzed asymmetric hydroformylation of
heterocyclic olefins. High-pressure (HP)-NMR and HP-IR spectroscopy
under 5–10 bar of syngas has been employed to characterize
the corresponding catalyst resting state with each ligand. Indole-based
ligands <b>L1</b> and <b>L2</b> led to selective <i>ea</i> coordination, while the xanthene derived system <b>L3c</b> gave predominant <i>ee</i> coordination. Application
of the small bite-angle ligands <b>L1</b> and <b>L2</b> in the highly selective asymmetric hydroformylation (AHF) of the
challenging substrate 2,3-dihydrofuran (<b>1</b>) yielded the
2-carbaldehyde (<b>3</b>) as the major regioisomer in up to
68% yield (with ligand <b>L2</b>) along with good ee’s
of up to 62%. This is the first example in which the asymmetric hydroformylation
of <b>1</b> is both regio- and enantioselective for isomer <b>3</b>. Interestingly, use of ligand <b>L3c</b> in the same
reaction completely changed the regioselectivity to 3-carbaldehyde
(<b>4</b>) with a remarkably high enantioselectivity of 91%.
Ligand <b>L3c</b> also performs very well in the Rh-catalyzed
asymmetric hydroformylation of other heterocyclic olefins. Highly
enantioselective conversion of the notoriously difficult substrate
2,5-dihydrofuran (<b>2</b>) is achieved using the same catalyst,
with up to 91% ee, concomitant with complete regioselectivity to the
3-carbaldehyde product (<b>4</b>) under mild reaction conditions.
Interestingly, the Rh-catalyst derived from <b>L3c</b> is thus
able to produce both enantiomers of 3-carbaldehyde <b>4</b>,
simply by changing the substrate from <b>1</b> to <b>2</b>. Furthermore, 85% ee was obtained in the hydroformylation of <i>N-</i>acetyl-3-pyrroline (<b>5</b>) with exceptionally
high regioselectivities for 3-carbaldehyde <b>8Ac</b> (>99%).
Similarly, an ee of 86% for derivative <b>8Boc</b> was accomplished
using the same catalyst system in the AHF of <i>N-</i>(<i>tert</i>-butoxycarbonyl)-3-pyrroline (<b>6</b>). These
results represent the highest ee’s reported to date in the
AHF of dihydrofurans (<b>1</b>, <b>2</b>) and 3-pyrrolines
(<b>5</b>, <b>6</b>)