Angewandte
Research Articles
Chemie
into a proper position to enable
abstraction of a hydride. The an-
gles of Rh-C-CH3, which corre-
spond to the distance between
Rh···b-H, have been shown as q in
3R/4R and 3S/4S. The b-H elimi-
nation will occur only when this
angle is small enough. The TS3S is
4.2 kcalmolÀ1 less stable than
TS3R, strongly indicating the ste-
reoselective formation of the R-
enantiomer. The Rh-P bond in the
TS3S must dissociate to effectuate
the hydride transfer, since other-
wise the methyl group of the sub-
Figure 2. Optimized structures for the competing transition states.
strate would overlap with the methyl group of the catalyst. Conclusion
This is additionally illustrated by the opposite relative
stabilities of 4R and 4S: while in the latter the rhodacycle is
In summary, we have realized the first enantioselective
intramolecular hydroacylation reaction of 3-enals for the
À
closed, the former cannot form a proper Rh C bond due to
the potential overlap of the CHCH3 group with the t-Bu group
of the catalyst.
construction of C3-chirogenic cyclopentanones. The reaction
proceeds through alkene isomerization via a five-membered
rhodacycle intermediate. The C3-chirogenic and C3,C5-chiro-
genic products are obtained with satisfactory yields, diaste-
reoselectivities, and enantioselectivities (up to 99/1 er). We
have also proposed a catalytic mechanism for the reaction and
have rationalized the outcome of the enantioselectivity based
on theoretical calculation.
Further rearrangements are necessary to place the newly
=
formed Rh-H and C C bonds in a proper position for the
hydrorhodation resulting in 7. There are numerous possibil-
ities that are illustrated by computing different rearrange-
ments leading to 7 for the R and S pathways. In the
transformations computed for the R-pathway, b-H elimina-
tion of the agostic intermediate 4R results in the Rh hydride
=
5R with the coplanar Rh-H and C C bonds. However, to
avoid the reverse transformation via hydrorhodation, the
double bond must first rotate via TS5R yielding 6R. The latter
gives the rhodacycle 7R in a hydrorhodation via TS6R, and
after reductive elimination provides the reaction product 2aR
and releases the catalyst. For the S-pathway another conse-
quence for the catalytic steps was computed. The agostic
intermediate 4S can undergo b-H elimination and reductive
elimination providing a coordinated 4-enals. Rotation of the
aldehyde group or small relocation would give 6S upon
hydrorhodation via TS6S yielding 7S, and eventually the
reaction product 2aS. It can be seen that the free energies of
either of the computed pathways are much lower than those
of the transition states of the rate-limiting steps. Hence, they
do not affect the origin of the stereoselection.
Acknowledgements
This work was supported by National Key R&D Program of
China (No. 2018YFE0126800), National Natural Science
Foundation of China (Nos. 21620102003, 21831005,
91856106, 21991112, 22071150), and Shanghai Municipal
Education Commission (No. 201701070002E00030). We
thank the Instrumental Analysis Center of Shanghai Jiao
Tong University. We acknowledge the generous gifts of the P-
chirogenic bisphosphine ligands from Nippon Chemical
Industrial Co. Ltd.
Conflict of interest
The optimized structures with selected interatomic dis-
tances for the competing transition states TS3S and TS3R has
been shown in Figure 2. In TS3S, approach of the methyl
group of the catalyst to the Rh atom (to enable further
hydride transfer) requires dissociation of the catalyst chelate
cycle leading to an increase in one of the Rh-P interatomic
distances to 2.73 . In TS3R, this interatomic distance is only
2.49 (i.e. it is 0.24 shorter). Maintaining the same Rh-P
distance in the TS3S would require the methyl groups of the
catalyst and the substrate to approach at 1.94 (2.18–0.24),
and it is known that a weak attraction between two aliphatic
protons in the range 2.3–2.7 switches to repulsion if they are
closer than 2.1 .[12]
The authors declare no conflict of interest.
Keywords: b-H elimination ·alkene isomerization ·
cycloketones ·hydroacylation ·rhodacycle
[1] a) T. I. Richardson, J. A. Dodge, G. L. Durst, L. A. Pfeifer, J.
Shah, Y. Wang, J. D. Durbin, V. Krishnan, B. H. Norman, Bioorg.
Franchini, L. I. Manasieva, P. Fossa, E. Cichero, G. Marucci,
55, 23; f) M.-L. Tang, C. Zhong, Z.-Y. Liu, P. Peng, X.-H. Liu, X.
Angew. Chem. Int. Ed. 2021, 60, 8997 –9002
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