Iterative Dual-Metal and Energy Transfer Catalysis Enables Stereodivergence in Alkyne Difunctionalization: Carboboration as Case Study

Stereochemically defined tetrasubstituted olefins are widespread structural elements of organic molecules and key intermediates in organic synthesis. However, flexible methods enabling stereodivergent access to E and Z isomers of fully substituted alkenes from a common precursor represent a significant challenge and are actively sought after in catalysis, especially those amenable to complex multifunctional molecules. Herein, we demonstrate that iterative dual-metal and energy transfer catalysis constitutes a unique platform for achieving stereodivergence in the difunctionalization of internal alkynes. The utility of this approach is showcased by the stereodivergent synthesis of both stereoisomers of tetrasubstituted β-boryl acrylates from internal alkynoates with excellent stereocontrol via sequential carboboration and photoisomerization. The reluctance of electron-deficient internal alkynes to undergo catalytic carboboration has been overcome through cooperative Cu/Pd-catalysis, whereas an Ir complex was identified as a versatile sensitizer that is able to photoisomerize the resulting sterically crowded alkenes. Mechanistic studies by means of quantum-chemical calculations, quenching experiments, and transient absorption spectroscopy have been applied to unveil the mechanism of both steps.

T etrasubstituted olefins are pivotal building units of biologically active, and functional materials and strategically important for the rapid assembly of chiral (3D) molecules upon selective functionalization of the C−C double bond (Figure 1). 1,2However, the development of selective methods for their preparation remains a considerable challenge.Traditional methods for olefin preparation (e.g., Wittig, Peterson, Julia) are inefficient for this class of substrates because the high steric crowding around the C�C generates energetically demanding transition states and deviation of the olefinic core from planarity. 3Even more difficult is the development of flexible methods enabling stereodivergent access to densely functionalized tetrasubstituted olefins from the same precursor. 4Indeed, the design of stereodivergent methods for the synthesis of tetrasubstituted olefins is very appealing because they can provide orthogonal exit vectors to explore new chemical space, which may be exploited for streamlining diversity-oriented library development. 5he transition-metal-catalyzed difunctionalization of internal alkynes represents an archetypal approach for the assembly of tetrasubstituted olefins. 6However, the inherent syn-stereochemical outcome of the syn insertion across the alkyne of the organometallic species renders this approach unfit for accessing the unconventional anti-addition stereochemistry (Scheme 1A).6a,7 Therefore, the preparation of both E and Z isomers often requires using different synthetic routes and two different sets of precursors.The selective photoisomerization of alkenes, which exploits excited-state reactivity via visible-light-mediated energy transfer (E n T) catalysis, has recently emerged as a potential solution to this fundamental limitation. 8A key approach to gain directionality in the isomerization is the disruption of conjugation of one isomer after triplet sensitization caused by noncovalent interactions, either destabilizing (e.g., A 1,3 strain in styrenes) 9 or stabilizing, 10 thus resulting in a negligible re-excitation of the final product that accumulates in the reaction mixture.However, this approach to geometry control remains largely limited to diand trisubstituted olefins, while its extension to tetrasubstituted ones is much more challenging because of steric interactions in the ground state (Scheme 1A).Recently, Gilmour et al. devised an elegant photoisomerization of trisubstituted β-boryl acrylates under E n T catalysis that takes advantage of an attractive n O → p B interaction between the CO group and B to break conjugation (Scheme 1B). 11During the preparation of this manuscript, Gilmour et al. reported the photoisomerization of tetrasubstituted α-fluoro β-borylacrylic acid derivatives. 12Nevertheless, steric constraints still present a major hurdle in alkene photoisomerization, and its application to tetrasubstituted alkenes still remains a highly coveted milestone. 10,11he exceptional versatility of the C−B bond in stereospecific cross-couplings, 13,14 the rich chemistry of the carbonyl group, and the unique umpolung of the α,β-unsaturated carbonyl system 15 harnessing the possibility to incorporate electrophiles into the β-position of the enone fragment after elaboration of the C−B bond render tetrasubstituted β-boryl acrylates ideal synthons en route to fully substituted functionalized olefins. 16owever, their preparation is challenging and typically requires indirect multistep approaches, such as the Miyaura borylation from preformed stereodefined alkenyl halides. 17−20 The Cucatalyzed B 2 pin 2 -carboboration of internal alkynes has emerged as one of the most efficient means of generating tetrasub-stituted alkenyl boronic esters, 21−23 but its extension to electron-deficient alkynoates remains largely elusive with no reports to date. 23,24This lack of success is likely a consequence of the presence of the CO 2 R group, which on the one hand reduces the already intrinsically poor nucleophilicity of the βboryl alkenyl−Cu intermediate, thereby preventing its reaction with electrophiles, 25 and on the other hand may promote E/Z isomerization of the alkenyl−Cu complex intermediate via Cu−allenolate species, thus compromising the stereoselectivity. 26e sought to develop an iterative catalytic alkyne difunctionalization/E n T photoisomerization as a general platform for achieving stereodivergence in the assembly of tetrasubstituted alkenes from the same alkyne precursor, thus circumventing the current need to prepare both isomers by different routes.These expectations were borne out in practice through the sequential catalytic carboboration and E n T photoisomerization that provides stereodivergent access to tetrasubstituted β-boryl acrylates from internal alkynoates (Scheme 1C).The synergistic combination of Cu and Pd catalysis 27,28 facilitates the otherwise unfeasible carboboration of the electron-deficient alkyne via transmetalation of the alkenyl−Cu intermediate with organo-Pd II species.An Ir complex was identified as an efficient sensitizer for the selective photoisomerization of the resulting tetrasubstituted alkenyl boronic esters under blue light irradiation (typically >98% selectivity).The global method combines broad substrate scope and applicability to complex multifunctional drug-like molecules.Transient absorption spectroscopy and quantum chemical calculations provide mechanistic insights for both steps.
■ RESULTS AND DISCUSSION 1. Optimization Studies.1.1.Carboboration.24j Although some carboboration (CB) product (Z)-3a was formed, the reaction gave mainly the hydroboration (HB) product (Z)-6a (CB/HB = 19:81) with low conversion (32% mixture yield, entry 1).Larger quantities of electrophile or base did not result in significant improvements (see the Supporting Information).This is consistent with the low nucleophilicity of the alkenyl−Cu(I) intermediate.However, a simple addition of 5 mol % PdCl 2 (PPh 3 ) 2 to the reaction media led to a dramatic increase in reactivity and CB-selectivity, which afforded the CB product syn-(Z)-3a in 84% yield (entry 2).This is likely because of the engagement of Pd through transmetalation between alkenyl−Cu(I) and methyl−Pd(II) catalytic intermediates.Other Pd complexes, such as the electron-rich [IPrPdCl 2 ] 2 (69%, entry 3) or the Buchwald precatalyst PCy 3 •Pd•G3 (57%, entry 4), led to slightly lower yields (see the Supporting Information for full studies).The use of Pd(OAc) 2 in combination with additional PCy 3 (10 mol %) led to the CB product (Z)-3a in 91% yield (entry 5), which was established as optimized conditions.
The application of this protocol to benzyl bromides was tested in the reaction with 1a with benzyl bromide, which afforded the CB product (Z)-4a with complete syn stereoselectivity but a low yield (47%, entry 6).This result revealed a significant dependence of the catalyst over the electrophile employed.However, the reactivity was fully restored by simply adjusting the Pd source to PdCl 2 (PPh 3 ) 2 (entries 7 and 8) and the ligand (XantPhos), which afforded (Z)-4a in 94% yield (entry 9).Other bisphosphine ligands were less efficient (dppbz, 25%, entry 10).
noncovalent interaction in the E-isomer instead of A 1,3 strain, since E/Z mixtures would be obtained in this case. 8,9. General scope.2.1.Carboboration.The results of an examination of the scope of the B 2 pin 2 -carboboration of various alkynes are presented in Scheme 2, which show complete regio-and syn stereoselectivity for all the substrates examined.Initially, we focused our attention to the methylboration protocol owing to the privileged presence of methyl groups in many drug candidates due to its ability to modulate physicochemical properties of pharmaceuticals. 34enerally, uniformly good yields were observed for several alkynes (Scheme 2A), including those bearing α-branched alkyl substituents at either the carbon triple bond or the ester group [(Z)-3b, 77% and (Z)-3c, 91%].The method is tolerant of potentially sensitive groups in the presence of Pd, such as alkyl chlorides [(Z)-3d, 68%], and base-sensitive aliphatic nitriles [(Z)-3e, 86%].Alkynes embedded in complex chiral molecules, such as the α-tocopherol derivative, underwent methylboration in good yield with complete preservation of the stereochemical integrity [(Z)-3f, 70%].
2.2.Photoisomerization.We next explored the efficiency of photoisomerization for a selected series of methyl, benzyl, and aryl alkenyl boronic esters.We initially tested alkenyl boron compounds substituted with a methyl group (Scheme 3A, 3a− 3e).First, (E)-3a was isolated as a pure stereoisomer (E/Z > 98:2) in quantitative yield after irradiation.The cyclohexylderived alkenyl boronic ester yielded the corresponding product with lower stereoselectivity (E/Z = 85:15), likely because of the strong deviation from planarity in (Z)-3b imposed by the cyclohexyl chain.However, stereochemically pure (E)-3b could be further isolated by flash chromatography (72% yield, E/Z > 98:2).Isomerization of a cycloheptyl alcohol ester afforded (E)-3c as a pure stereoisomer in excellent yield (97%).Finally, when Cl-and CN-containing (Z)-3d and (Z)-3e were submitted to the isomerization conditions, the corresponding E isomers were isolated with complete stereochemistry in 91% and quantitative yields, respectively.
Second, we explored selected benzylborylated products from Scheme 2 (Scheme 3B, 4a−k).As previously mentioned, benzyl derivative (E)-4a was isolated as a spectroscopically pure isomer (E/Z > 98:2) in quantitative yield under the optimized reaction conditions.Structural effects were observed during the photoisomerization of (Z)-4b, which resulted in a mixture of both isomers in an E/Z = 75:25 ratio in the photostationary state.Despite this, the desired (E)-4b product could be isolated as a pure stereoisomer in 69% yield. 18When the bromine atom was located at the para position, photoisomerization to (E)-4c took place in quantitative yield with complete stereoselectivity.Related substrates, such as a bis(fluorinated benzyl) derivative, afforded (E)-4d in 92% a Determined in the reaction crude by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard.
yield.Interestingly, when other groups were placed at the ortho position of the phenyl ring, the steric hindrance was well tolerated [(E)-4e and (E)-4f, 90% and 89%, respectively], with the formation of the E isomer in spectroscopically pure form (E/Z > 98:2).On the contrary, a more sterically hindered 2,4,6-trimethyl-benzyl-containing olefin underwent incomplete isomerization, albeit the (Z)-4g product could be isolated in its stereochemically pure form in 59% yield after purification.The reaction tolerated the presence of both internal and terminal alkenes, such as those contained in products (E)-4i and (E)-4j (97% and 98%, respectively), and internal alkynes, as in the case of product (E)-4k (92% yield).Finally, tetrasubstituted olefins bearing an aryl unit were subjected to photoisomerization (Scheme 3C, 5a−k).Notably, the reaction took place regardless of the electronic nature of the aryl substituent to afford the corresponding E isomer in high yields and complete stereoselectivity.Products bearing a phenyl group [(E)-5a, 97% yield], electron-rich aromatic rings [(E)-5b−d, 93% quantitative, and 87% yields, respectively), and electron-withdrawing substituents [(E)-5g,h, quantitative and 96% yield, respectively) were isolated as single stereoisomers.When we studied a 2-thiophene derivative, we observed a E/Z = 66:34 ratio in the photostationary state, although stereochemically pure (E)-5e was isolated in 52% yield.This result suggests a strong S−B interaction in the Z isomer, which is in competition with the O−B dative bond in the E isomer.Finally, the alkyne-containing (E)-5i product was obtained with excellent stereoselectivity, and the silylsubstituted internal alkene afforded (E)-5k, thereby showing a synthetic alternative for the stereodivergent access to 1,1bismetalated tetrasubstituted alkenes. 35

Formal Stereodivergent Approach to Complexity.
To further highlight the utility of this two-step strategy, we sought to prepare both stereoisomers of the same complex molecule.Ideally, these would come from alkynoates containing elaborate substituents with base-sensitive stereocenters and functional groups of diverse nature, thereby taking advantage of all the possible elements of structural diversity (Scheme 4).The assembly of both E and Z isomers of the tetrasubstituted alkenyl boronate contained in estrone derivatives 3g and 5l could be easily performed when MeI and BnBr were employed as the reactive electrophiles.Importantly, we observed complete functional tolerance under the reaction conditions since no side reactions from boryl-copper-promoted addition to the ketone or alkylation at the α-position through enolate formation were observed.Then, we studied derivatives from indomethacin, an anti-inflammatory drug, by using BnBr and PhI as model electrophiles (compounds 4n and 5m, respectively).The corresponding Z isomers of both products were obtained with complete syn stereoselectivity and high yields (89% and 91%, respectively).Equally efficient was the modification of the C−C double bond geometry of the tetrasubstituted olefin core using our optimized reaction conditions for the photoisomerization step, which led to the desired products (E)-4n and (E)-5m with complete E stereoselectivity and yields higher than 80%.The Gibberellic acid derivative (Z)-5n decorated with a pendant alkynoate motif was also obtained in 68% yield by means of the carboboration reaction using PhI as the electrophile.Complete stereoselectivity was obtained for the inversion of the stereochemistry at the tetrasubstituted alkene moiety after isomerization with PC-7 under blue light, thereby enabling the isolation of (E)-5n in 94% yield.Importantly, all other stereocenters and functionalities were well tolerated.Finally, we explored the stereodivergent synthesis of the tetrasubstituted alkenyl boronate 5o using a derivative of α-tocopherol, a form of vitamin E, and PhI as the electrophile, which led to the corresponding Z and E isomers in 74% and quantitative yield, respectively.

Mechanistic Studies. 3.1. Computational Studies.
To further understand the mechanisms and observed selectivities of the syn-carboboration and photoisomerization reactions discussed in the preceding sections, we also performed quantum chemical calculations (see the Supporting Information for computational details).First, we sought to investigate to what extent the presence of the ester functionality next to the C(sp 2 )�Cu bond affects the nucleophilicity of the intermediate alkenyl−Cu(I).To this end, we compared the susceptibility for an electrophilic attack by calculating the corresponding nucleophilic Fukui functions (f _ ) 36 for model substrates bearing methyl, phenyl and methyl ester substituents (Figure 2a).From this analysis, we observed that the nucleophilicity of the C�α position decreases from the methyl (+0.20) to the phenyl (+0.17) and methyl ester (+0.14) depending on the capacity to delocalize the negative charge at this position, which points to a less reactive intermediate with electrophiles in the latter case.
Then, we compared the reaction profiles of Cu-catalyzed carboboration (Figure 2b, red pathway) and the effect of transmetalation with palladium (Figure 2b, blue pathway).To reduce the computational cost, we made three simplifications: (a) we used phenyl iodide as the sole electrophile, (b) we replaced the propyl chain of 1a with a methyl group, and (c) we removed the gem-dimethyl groups of XantPhos.None of these changes have a substantial impact on the reactivity, thus, still providing valid insight.First, we explored the Cu-catalyzed reaction.Coordination of PhI to the alkenyl−Cu(I) I1−Cu leads to the formation of a weakly bound van der Waals complex I2.Oxidative addition of PhI takes place to form I3, an intermediate Cu(III) species in which the XantPhos ligand adopts monodentate coordination.This is the rate-determining step of the reaction with an activation barrier of 11.8 kcal mol −1 .Reductive elimination, followed by decoordination of the Cu catalyst, would lead to formation of the final adduct I6.
Next, we investigated the effect of Pd transmetalation from the intermediate alkenyl−Cu(I) I1−Cu.Starting from the Pd(0)/XantPhos complex (I1−Pd), the oxidative addition of PhI proceeds through a lower activation barrier of 5.3 kcal mol −1 because it is both kinetically and thermodynamically more favorable than the equivalent process with Cu.Transmetalation, which occurs via the formation of a bimetallic species upon reaction with I1−Cu, is a highly exergonic process in which the Cu center is displaced to form the alkenyl−Pd(II) intermediate I10.Then, reductive elimination and Pd detachment yield the alkenyl boronate I6.
From a comparison of the two pathways, the reactivity is enhanced upon the addition of palladium because of two key features: first, the oxidative addition step in which the large difference (6.5 kcal mol −1 ) between the activation barriers for Cu and Pd clearly promotes the reaction with the latter, and second, transmetalation, which is thermodynamically very favorable, thereby meaning that as soon as the alkenyl−Cu(I) I1−Cu is formed, it will be converted into the alkenyl−(II) intermediate I10.Therefore, with both I1−Cu and I1−Pd present, PhI will preferentially react with the latter and, once I8 is formed, Cu−Pd transmetalation and reductive elimination have a clearly downhill energy profile.
We next sought to unveil the origin of the excellent stereoselectivity of Ir-catalyzed photoisomerization.A density functional theory (DFT)-based analysis showed that, regardless of the substituent at the C α position (Me, Bn, or Ph), the E isomers are ca.4 kcal mol −1 more stable than their Z counterparts (see the Supporting Information for further details).In the Z isomers, the atoms of the Bpin group are coplanar with those of the acrylate moiety.In contrast, in E isomers, the Bpin group adopts a perpendicular orientation.This gives rise to a stabilizing intramolecular interaction between the p B orbital and the lone pairs at the oxygen in the methyl ester, as corroborated by NBO and wave function topological analyses (Figure 3, top). 11o gain further insight into the mechanism of the photoisomerization and the role of the photocatalyst, we mapped the topography of the lowest-lying excited singlet and triplet states of s-cis-3a′ using multiconfigurational approaches (Figure 3, bottom).Pleasingly, MS-CASPT2//SA-CASSCF predicts the same relative stability of the E and Z isomers as DFT.By starting from either of the ground-state minima, (Z)s-cis-3a′ and (E)-s-cis-3a′, optimization of the T 1 (π,π*) state leads to the population of an excited-state minimum at 59.6 kcal mol −1 .This structure is characterized by a 90°twist of the C−C double bond, thereby suggesting the formation of a triplet biradical species.At this point, the S 0 and T 1 states are nearly degenerate, which allows intersystem crossing to the ground state and regeneration of the planar acrylate.
Importantly, the participation of excited singlet states in the photoisomerization can be safely ruled out because of their high energy, which surpasses both the employed excitation wavelength (ca.450 nm, 63.5 kcal•mol −1 ) and the triplet energy of the photocatalyst PC-7 (62 kcal•mol −1 ).This is also true for the lowest 3 n,π* state.Therefore, the reaction must proceed through the T 1 state.Under this scenario, at the position of the (Z)-s-cis-3a′ minimum, the energy difference between the S 0 and T 1 states (83.7 kcal•mol −1 ) prevents a direct vertical triplet energy transfer mechanism with PC-7.Therefore, the photosensitization process likely occurs through a nonclassical triplet energy transfer. 37This model has been previously proposed for other endothermic energy transfer processes, 38 and implies the population of excited rotovibrational levels at the S 0 state by thermal activation ("hot-band" model) involving single and double bond torsions.From the thermally activated state of the acceptor, the pathway for the population of the T 1 state will be lower in energy, for which the existence of a minimum in the triplet potential energy surface is not required. 39After photoisomerization, the corresponding (E)-s-cis-3a′ product displays a strong interaction between the carbonyl group and the boron atom, which is translated into a higher energy difference between the S 0 and T 1 states.Additionally, this interaction is likely responsible for preventing torsions of the single and double bonds that allow for the thermal activation required in the nonclassical energy transfer, explaining the selective sensitization of the Z isomer.The steric shielding effect of the Bpin group over the double bond after photoisomerization could also prevent orbital overlap between the olefin and the photocatalyst, which is an aspect crucial for the energy transfer to take place.4a The same qualitative analysis applies for s-cis-5a′ (bearing a phenyl group, see the Supporting Information for further details) that, because of the lack of conjugation between the phenyl group and the acrylate moiety (with dihedral angles around 54°), the substituent at Cα does not have a substantial effect on the triplet energies.Therefore, after nonclassical energy transfer with the Z-alkenyl boronate, the triplet manifold would be populated.From that point forward, intersystem crossing to the ground state would lead to the formation of the E isomer in a thermodynamically driven process.

Photophysical Studies.
To further understand the photoisomerization step, we conducted some photophysical studies using both isomers of alkenyl boronate 3a and the photocatalyst PC-7 (Figure 4).The UV−vis spectrum of PC-7 shows a broad shoulder at ∼400 nm, while its luminescence spectrum (λ exc = 400 nm) displays two maximum peaks at ∼475 and 500 nm.A calculated triplet excited-state energy (E T ) value of 63 kcal•mol −1 (Figure 4a) agrees with the reported value. 33In addition, a luminescence lifetime (τ L ) of 167 ns (Figure 4b) and a luminescence quantum yield (φ L ) of 0.10 in aerated acetonitrile were obtained.Quenching experiments with O 2 (Figure 4b, inset) suggested the triplet nature of the observed signal with lifetimes of τ = 1700 and 40 ns in deaerated and purged O 2 solutions, respectively, and a quenching constant of k q = 2.67 × 10 9 M −1 s −1 .Indeed, this is in accordance with the fact that these systems undergo ultrafast intersystem crossing to populate the triplet excited state by means of the heavy atom effect. 40Transient absorption spectroscopy (TAS) measurements for PC-7 (λ exc = 355 nm) under an inert atmosphere (where φ L increased up to 0.90) revealed a positive transient absorption (TA) band at 350 nm and a negative TA band at 475−500 nm, which correspond to the triplet and phosphorescence, respectively (Figure 4c), which present a first-order kinetic transient (and luminescence) lifetime (τ) of 1700 ns (Figure 4d).
Then, triplet quenching experiments by TAS were performed employing (Z)-3a or (E)-3a alkenes as quenchers (Figure 5).The addition of (Z)-3a promoted a highly efficient quenching of the 3 PC-7* TA signal (Figure 5a) with k q = 1.72 × 10 8 M −1 s −1 (Figure 5d).We did not observe new signals resulting from PC-7 upon addition of (Z)-3a (see the Supporting Information for details).In addition, the dynamic quenching observed on the transient decay traces at 380 and 500 nm followed monoexponential functions (Figure 5b).Consequently, we discarded the possibility of a photoinduced electron transfer (PET) process. 41Additionally, the absorption of either (Z)-or (E)-3a alkenes and the emission band of the PC-7 do not overlap (Figure 4a), so a Forster resonance energy transfer (FRET) mechanism is not likely to occur under the reaction conditions. 42These pieces of evidence strongly suggest a Dexter energy transfer as the operative mechanism for the photoisomerization process. 42In contrast, no changes were observed upon addition of the (E)-3a isomer (Figure 5c), thereby showing a negligible interaction between the substrate and the photosensitizer after isomerization (k q = 1.34 × 10 6 M −1 s −1 , Figure 5d), which is consistent with the computational studies.
electron-deficient internal alkynes was selected as a suitable test for this design principle for two main reasons: (1) The unreactive nature of internal alkynoates toward catalytic carboboration, which was addressed by using cooperative Cu/Pd catalysis, is a strategy that overcomes the sluggish reactivity of the β-boryl alkenyl−Cu intermediate and its configurational lability to provide the first general selective carboboration of electron-deficient alkynes with carbon electrophiles, including MeI, benzyl bromides, or ArI.(2)  The photoisomerization of the resulting tetrasubstituted βboryl acrylates via E n T catalysis has been accomplished with excellent stereocontrol upon identification of an Ir complex that is competent as a versatile sensitizer for this class of challenging, sterically crowded alkenes.This platform enables late-stage modifications of complex alkynoates and enables stereodivergent access to E and Z isomers of densely functionalized tetrasubstituted β-boryl acrylates with high synthetic versatility.Computational analysis supports the viability of a phosphine-assisted Cu/Pd transmetalation step in the carboboration process, as well as the thermodynamic preference for the E isomer via a n O → p B interaction.Analysis of the excited-state potential energy surfaces state suggests that sensitization from the triplet excited state of the Ir likely occurs through "nonclassical" energy transfer.Finally, photophysical studies show that the reaction occurs by quenching of the triplet excited state of the Ir photocatalyst via a Dexter-type mechanism.
Experimental details, including complete reaction optimization studies, experimental procedures, and spectral data for products, and computational details, including methodology, conformational analysis, and complete excited-state potential energy surfaces and Cartesian coordinates of optimized structures (PDF) ■ AUTHOR INFORMATION

Scheme 1 .
Scheme 1. Approaches to Stereodivergence toward the Synthesis of Tetrasubstituted Olefins: (a) Merging Organometallic and Energy Transfer Catalysis, (b) Boron-Enabled Photoisomerization by Energy Transfer Catalysis, and (c) Iterative Dual-Metal and Energy Transfer Catalysis for β-Boryl Acrylates (This Work)

Scheme 4 .
Scheme 4. Application of the Formal Stereodivergent Carboboration to Complex Molecules

Figure 2 .
Figure 2. Computational studies on the carboboration reaction.(a) Nucleophilic condensed Fukui functions for alkenyl boronates bearing a methyl (left), phenyl (middle), and methyl ester (right) substituents at the α-position.Larger values are related to larger nucleophilicity (hydrogen atoms are omitted for clarity).(b) Reaction profiles for the Cu-catalyzed cross-coupling (red) and Cu/Pd-catalyzed cross-coupling (blue).Gibbs free energies at 298.15 K are given relative to the sum of all reagents (I1−Cu + I1−Pd + PhI + PhCH 3 ) at infinite distance.

Figure 3 .
Figure 3. Computational studies on photoisomerization.Top: M06-L/cc-pVTZ electron density at the B−O bond critical point and second-order interaction energies between represented NBO orbital pairs for (E)-s-cis-3a′.Bottom: MS-CASPT2//SA-CASSCF relative energies of the lowest-lying singlet and triplet states at the critical points along the Z → E photoisomerization of s-cis-3a′.Gray, dashed arrows show the vertical and adiabatic triplet energies of (Z)-s-cis-3a′.

Table 1 .
Optimization Studies for the syn-Carboboration of Alkyne 1a a

Table 2 .
Optimization Studies for Z-to-E Photoisomerization