COMMUNICATIONS
Ynones Merge Activation/Conjugate Addition of Chalcogenoborates
entry 4). A similar result was attained in the b-sele- spect to aminoboronates[16] or phosphinoboronates.[17]
niation of 12 with the corresponding ratio 13-Z/13- In parallel, we have recently unravelled theoretically
E=92/8 (Table 1, entry 5). Quantitative conversion the mechanism for the selenoboration and thiobora-
and stereoselectivity were achieved for the 1,3-diphe- tion of a,b-unsaturated aldehydes and ketones, dem-
nylprop-2-yn-1-one substrates 14 and 18 (Table 1, en- onstrating the activation mode of chalcogenoborate
tries 6 and 8) with a slight decrease in stereoselectiv- reagents by the carbonyl group in a,b-unsaturated
ity on the transformation from 16 to 17-Z/17-E=90/ carbonyl compounds (Figure 2, right).[18,19] Here we
10 (Table 1, entry 7). The full characterization of 19- describe a mechanistic pathway for assembly of the
Z, from its exclusive formation, included diffraction chalcogenoborates and ynones that also rationalizes
X-ray data (Figure 1).
the favored stereoselectivity on (Z)-b-(arylseleno)-
The straightforward reactivity between ynones and a,b-unsaturated ketones.
PhSe-Bpin (1) simplified previous attempts to obtain
By means of DFT studies (see the Supporting In-
(Z)-a,b-(arylseleno)-a,b-unsaturated ketones via ad- formation for computational details) we were able to
dition of selenoesters to alkynes catalyzed by copper envisage the profile for the reaction of the model
(I).[14] Our next goal was to extend the assembly pro- alkyne 1-(4-methylphenyl)-3-phenyl-2-propyn-1-one
tocol to chalcogenoborates PhS-Bpin (2) and BnS- (18) with PhSe-Bpin (1) (Scheme 3). Three reaction
Bpin (3) to synthesize vinyl sulfides from accessible pathways are possible concerning the two electrophil-
ynones. Table 2 includes the most remarkable data ic functionalities of the substrate, the triple bond and
from this study which highlights that the addition of the carbonyl group. The first step of the reaction is
ArS groups to the a,b-acetylenic ketones takes place the activation of the boron atom of reagent 1 with the
regioselectively in the Cb position with a stereoselec- oxygen atom of the carbonyl group that occurs
tivity Z/E of ca. 3/1, independent of the nature of the through a first transition step (TS1) and leads to the
Ar group in the thiodioxaborolane reagent. The ali- intermediate I1. Then, two pathways are possible:
phatic substituents in substrates 10 and 12 favored The attack of the nucleophilic -SePh moiety on the
the relative formation of the E isomer (Table 2, en- carbonyl group (TS2 1 2) or on the triple bond (TS2
tries 4 and 5). The trend to form the (Z)-a,b-(arylsul- 1 4). After the TS2 1 2 an intermediate I2 1 2 is
furo)-a,b-unsaturated ketone, as the major isomer, by formed. This intermediate can finally undergo proto-
mixing the thiodioxaborolanes and ynones, contrasts nolysis with methanol to form the 1,2-addition prod-
with the lower stereoselectivity observed in alterna- uct and the by-product pinBOMe. When we conduct-
tive methodologies such as addition of thiols to the ed an NMR experiment of 4 with PhSe-Bpin in tolu-
electron-deficient alkynes methyl propiolate and di- ene-d8, we were able to observe the formation of the
methyl acetylenedicarboxylate, in the presence of Ru I2 1_2 which after addition of MeOH was converted
catalysts.[15]
back to the ynone starting material (see the Support-
The favored formation of (Z)-vinyl selenides and ing Information). Considering the other pathway,
vinyl sulfides is opposite to the trend observed for the after the TS2 1_4 occurs, an allene intermediate is
(E)-vinylamines through b-amination of ynones with formed (I2 1_4). This intermediate can also undergo
Bpin-NMe2 and Bpin-NEt2 from the adduct [ROÀ! protonolysis with methanol but in this case by two
Bpin-NMe2] (Figure 2, left). This is probably due to faces, leading to two different transition states TS3
the different activation mode of the chalcogenoborate 1_4 Z and TS3 1_4 E that give rise to the isomers Z
reagents PhSe-Bpin, PhS-Bpin and BnS-Bpin, with re- and E of the final product respectively. This TS2 1_4
can also occur by the other face of the substrate,
giving rise to the other enantiomer of the I2 1_4 that
gives the energetically exact pathway.
Our experimental results show that the obtained
product for this reaction is the 1,4-addition product
with Z configuration excluding the formation of the E
isomer or the 1,2-addition product. These results are
in good agreement with our mechanistic proposal as
the pathway for the 1,2-addition is less favoured due
to the lower stability of the intermediate I2 1_2 and
¼
the high energy barrier for the TS3 1_2 (DG =
23.9 kcalmolÀ1). Moreover, the formation of the Z
versus the E isomer is favourable both kinetically
¼
(DDG =1.1 kcalmolÀ1)
and
thermodynamically
(DDG=2.7 kcalmolÀ1).
Figure 2. Activation modes of ynones and a,b-unsaturated
carbonyl compounds by chalcogenoborate (E=Se, S) and
aminoboronate reagents.
As a final conclusion we can now offer a more flex-
ible and reliable route to stereodefined (Z)-alkenyl
Adv. Synth. Catal. 2015, 357, 3098 – 3103
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3101
Civit, Marc G.
