Organic Letters
Letter
Table 1. Optimization of the Reaction between
Allenylboronic Acid Pinacol Ester and Cyclopentadiene
for the direct [2 + 2] cycloadditions were unsuccessful.
However, we were able to locate TSs that connected the [4 +
2
] adducts with some of the [2 + 2] adducts through [3,3]-
endo/
exo
19
a
b
sigmatropic rearrangements (Scheme 2). Figure 1 shows the
M062X/6-31G* free energy profile for the Diels−Alder
reactions and the corresponding rearrangements of the
cycloadducts. In agreement with the experiments, the trans-
formations with the lowest free energy barriers (ca. 30 kcal/
mol) are the formation of Diels−Alder products 5N and 5X.
The most stable products, however, are regioisomeric cyclo-
adducts 6E and 6Z, although both reactions are highly
exergonic. In contrast, the rearrangements of all [4 + 2]
products are endergonic and have very high activation barriers
entry
conditions
yield (%)
1
2
3
4
5
6
7
8
9
toluene, 200 °C, 1.5 h
86 (77)
87 (66)
59 (55)
56
66
0
47
76 (70)
0
50:50
50:50
50:50
50:50
50:50
−
50:50
50:50
−
50:50
50:50
60:40
60:40
toluene, 120 °C, 78 h
toluene, 200 °C, 1.5 h
MeCN, 200 °C, 2.5 h
DMSO, 200 °C, 0.5 h
water, 200 °C, 0.5 h
neat, 200 °C, 1.5 h
neat, 200 °C, 0.5 h, MW (400 W)
toluene, BF .Et O (5 mol %), 120 °C, 20 h
3
2
(
+
ca. 50 kcal/mol) due to their higher stability relative to the [2
2] isomers, which rules out these transformations.
10
11
12
13
toluene, Sc(OTf) (5 mol %), 120 °C, 20 h
20
39
56
88 (18)
3
20
toluene, Yb(thd) (5 mol %), 120 °C, 46 h
3
However, we cannot discard the possibility that these
unexpected theoretical findings suggest a bifurcation or other
subtleties in the potential energy surface and intend to explore
toluene, AuCl (5 mol %), 120 °C, 30 h
toluene, AuCl (10 mol %), 120 °C, 30 h
a
All reactions were performed with 0.3 mmol of 4 and 5 equiv of 2 in
the presence of BHT (5 mol %) except for entry 3, in which no BHT
21
it in further detail with other techniques.
b
1
Table 2 collects the activation and reaction free energies at
the M062X/6-31G* level of theory for the reaction between
vinylboronate 1 and cyclopentadiene (2) as well as all studied
was added. Determined by H NMR; isolated yields are given in
parentheses
22
transformations for allenylboronate 4. In general, the relative
free energies obtained in the gas phase and in solution are very
similar. The Diels−Alder reaction of vinylboronate 1 has an
activation barrier around 3 kcal/mol lower than the one for
allenyl analogue 4, accounting for its higher experimental
reactivity. Regarding the possible transformations for 4, even
though products 6 are ca. 4 kcal/mol more stable than isomers
Scheme 2. Competitive Pathways Located for the Reaction
5
, the lower free energy barrier for the formation of the latter
explains the complete regioselectivity observed experimentally
⧧
(
selectivity in the Diels−Alder reaction can be rationalized by
the very small differences computed for the free energies of
TS5X and TS5N (endo/exo ratios 57:43 in the gas phase and
39:61 in toluene). Although the endo/exo preference for
formation of 5 varies with level of theory, the B3LYP and
ωB97XD functionals also correctly predict small ΔΔG (<0.7
Furthermore, in principle, due to the structural features of
allenes, the [2 + 2] cycloadditions with alkenes are thermally
1
5
⧧
allowed. Then, we envisaged eight different modes of
Fortunately, compound 5 was the only product found
experimentally, indicating that the studied reaction is both
completely regio- and periselective.
Figure 1 also shows the optimized geometries for selected
transition structures. The TSs for the formation of 5N and 5X
are asynchronous and present weak [4 + 3] C−B secondary
23
To gain a better understanding of the reaction between
allenylboronic acid pinacol ester (4) and cyclopentadiene (2)
interactions. In contrast, TS6E and TS6Z are much less
asynchronous. Although both FMO interactions are very
similar, the dominant interaction appears to be the one
between the LUMO of dienophile 4 and the HOMO of
cyclopentadiene, and the coefficients of the former confirm the
most electrophilic atom is the central carbon of the allene,
followed by the atom directly attached to the boron. On the
other hand, the terminal carbon seems to be the most
The TSs that connect the [4 + 2] and [2 + 2] adducts through
Cope [3,3]-sigmatropic shifts, TS5−7 and TS6−8, have
chairlike geometries.
(Scheme 1, eq b), we performed a computational study aiming
to assess all the possible reaction channels. We also compared
the results with those corresponding to vinylboronic acid
pinacol ester (1) (Scheme 1, eq a). The geometries of the
starting materials, products and transitions structures (TSs)
were optimized using the 6-31G* basis set and three different
16
17
18
functionals, B3LYP, ωB97XD, and M062X, in the gas
Reported thermochemical properties were calculated at 1 atm
and 298.15 K. In general, the results of the calculations were
consistent with the experimental findings, though B3LYP
predicted higher free energy barriers for the reactions and
lower relative stability for the products.
Many theoretical studies suggest that some cycloadditions of
allenes take place through stepwise mechanisms with 1,4-
2
1a,24
diradical intermediates.
We thus investigated such
The TSs for all modes of addition for the Diels−Alder
reaction between 2 and 4 were readily located. On the
contrary, all the numerous attempts to find the concerted TSs
competitive pathway for the reaction between pinacol
allenylboronate (4) and cyclopentadiene (2). The optimiza-
tions were performed with the unrestricted UB3LYP/6-31G*
5
082
Org. Lett. 2021, 23, 5081−5085