Parikh-Doering oxidation, and the resulting
aldehyde was purified by a simple workup with
sodium bisulfite. This aldehyde contains both a
syn- and an anti-b-hydrogen. Syn-selective dehydroformylation established the trisubstituted
olefin at the ring junction. To our surprise, however, the resulting allylic alcohol underwent transfer dehydrogenation in the same pot to yield
(+)-yohimbenone in 65% yield. Because dehydroformylation is faster than the allylic alcohol oxidation, either the allylic alcohol or enone product
could be selectively formed by controlling the
reaction temperature and stoichiometry of the
strained olefin acceptor ( 32).
Through experiments designed to probe the
mechanism, we obtained insight into why the
counterion and strained acceptor are critical in
diverting the acyl-RhIII-hydride intermediate
along the dehydroformylation pathway. Isotopic
labeling studies revealed that the deuterium label of aldehyde d-1q was incorporated into the
formyl group of the product d-6c. However, statistical scrambling occurred when protio-1q was
subjected to transfer hydroformylation in the
presence of deuterated methanol (Fig. 4A). Together, these results suggest that the aldehyde
proton is transferred to the product through the
intermediacy of 3-methoxybenzoic acid, which
can undergo proton exchange with methanol.
Experiments using stoichiometric Rh support
this mechanistic scenario (Fig. 4B). Combining
the Rh-source, 3-methoxybenzoic acid, and phos-
phine ligand resulted in an equilibrium mixture
of Rh complexes 8a and 8a′, each with 3-
methoxybenzoate counterions. Upon treatment
of this mixture with hydrocinnamaldehyde (1q),
we observed styrene (2q) in high yields along
with the regeneration of the benzoic acid deriv-
ative ( 33). Subsequent addition of PPh3 enabled
us to identify the organometallic product, Rh-
hydrido-carbonyl 9, which is a catalyst for
traditional hydroformylations ( 34). Although
stoichiometric dehydroformylation takes place
in the absence of the strained acceptor, our studies
on the catalytic process revealed a correlation
between the ring strain of the acceptor and the
selectivity for dehydroformylation versus decar-
bonylation. Therefore, we propose that stoichi-
ometric dehydroformylation in the absence of
acceptor is thermodynamically downhill and
reversible, but norbornadiene can irreversibly trap
the Rh-hydrido-carbonyl intermediate to prevent
decarbonylation and turn over the catalyst.
A proposed catalytic cycle for transfer hydrofor-
mylation is depicted in Fig. 4C. The neutral Rh
complex 8a activates the aldehyde C–H bond to
generate acyl-RhIII-hydride 8b. The 3-methoxy-
benzoate counterion can then undergo reductive
elimination with the hydride ligand to generate
acyl-RhI 8c and 3-methoxybenzoic acid ( 35). In
contrast, most hydroacylations and decarbonyla-
tions typically employ innocent counterions such
as Cl– and BF4–. De-insertion of CO and subse-
quent b-hydride elimination forges Rh-hydrido-
carbonyl 8e. Exchange of the olefin product
with norbornadiene (5a) generates 8f, which
irreversibly leads to the transfer hydroformyla-
tion product 6a through similar mechanistic steps
in reverse order (Fig. 4C). Thus, the ring strain
of the olefin acceptor and the ability of the
counterion to act as a proton shuttle by revers-
ible redox processes afford high reactivity and
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Fig. 4. Mechanistic studies.
(A) Deuterium labeling studies.
(B) Isolation of organometallic
intermediates. (C) Proposed