Catalytic Net Oxidative C–C Activation and Silylation of Cyclopropanols with a Traceless Acetal Directing Group

Abstract

Redox-neutral carbon–carbon (C–C) bond activation and functionalization strategies of cyclopropanols that give metallo homoenolate have offered merits to construct a range of useful β-functionalized ketones in an inverse-polarity fashion. Discovery and identification of oxidative C–C activation reactions of cyclopropanols that generate metallo enolate–homoenolate would provide an opportunity to afford α,β-difunctionalized ketones. We report catalytic, net oxidative C–C activation, and silylation of cyclopropanols with traceless acetal directing groups under consecutive Ir and Rh catalysis in regio-, stereo-, and chemo-selective fashion. In detail, Ir-catalyzed hydrosilylation of cyclopropyl acetates provides the acetal directing group in quantitative yield. Rh-catalyzed proximal C–C silylation of the resulting cyclopropyl silyl acetal produces the metallo enolate–homoenolate equivalent, dioxasilepine, which uniquely holds an interconnected β-silyl moiety and Z-vinyl acetal. Upon sequential treatment of a silaphile that removes the acetal directing group and electrophile, the seven-membered silicon-containing heterocycle, serving as the ketone α,β-dianion equivalent, delivers α,β-difunctionalized ketones. Scope of the hitherto unexplored reactivity of cyclopropanols toward net oxidative C–C silylation and the versatility of the resulting dioxasilepines were demonstrated. These include late-stage, net oxidative C–C silylation of biologically relevant molecules and facile production of a range of α,β-difunctionalized ketones. Preliminary mechanistic studies suggest that the C–C activation harnessing the electron-rich Wilkinson-type catalyst is likely the turnover-determining step and a Rh-π interaction is the key to the efficient metal insertion to the proximal C–C bond in cyclopropanols.

Graphical Abstract

INTRODUCTION

Carbon–carbon (C–C) bond activation and functionalization strategies of cyclopropanols^1–5 have offered merits to construct a range of useful β-functionalized ketones.^6–27 As depicted in Figure 1a, a formal charge affinity pattern of metallo homoenolate 2 differs from the location of negative charge of C-metallo enolate 1. Thus, the nucleophilic, metallo homoenolate 2²⁵ has served as an important inverse-polarity (i.e., umpolung)^28–30 synthon of Michael acceptors and can engage in various β-functionalization reactions, including addition reactions²⁷ or cross-coupling to form new C–C, C–N, and C–S bonds (Figure 1b.1).^26,31–36 Subsequently, metallo enolate–homoenolate 3 merging metallo enolate (tautomer of 1) and metallo homoenolate 2 has been introduced. This species holds two nucleophilic sites and thus can engage in α,β-difunctionalization through inverse-polarity β-functionalization and normal-polarity α-functionalization. Ryu and Sonoda first demonstrated that lithium enolate of β-lithio ketone 3a was produced through a stoichiometric protocol involving metal-halogen exchange of lithium enolates of β-stannyl 6 (Figure 1b.2, left).^37,38 Ogoshi reported the first catalytic generation of ketone α,β-dianion equivalents 3b via normal-polarity 1,4-disilylation of enones 7 under nucleophilic palladation conditions (Figure 1b.2, right).³⁹ In these studies, a high level of Z-enolate geometry was achieved by chelation or reagent control.

Figure 1.

(a) Formal charge affinity patterns of C-metallo enolate 1, metallo homoenolate 2, and metallo enolate–homoenolate 3. (b) Previous studies on redox-neutral C–C activation of cyclopropanols to give metallo homoenolate 2 for inverse-polarity β-functionalization and redox-neutral conversion of prefunctionalized ketones (6 and 7) to afford metallo enolate–homoenolates 3a and 3b, respectively, for α,β-difunctionalization. (c) Catalytic net oxidative C–C activation of cyclopropanols to generate ketone (Z)-metallo enolate–homoenolate equivalents III, which serve as α,β-dianion equivalents to provide a range of α,β-difunctionalized ketones 9.

In this work, we describe the hitherto unexplored reactivity of cyclopropanols through catalytic, net oxidative C–C activation and functionalization with a traceless directing group (DG) (Figure 1c). This oxidative C–C activation protocol can directly generate ketone metallo enolate-homoenolate equivalents from cyclopropanols 8 in regio-, stereo-, and chemoselective fashion, leading to α,β-difunctionalized ketones. Unlike previously developed, redox-neutral C–C activation methods (i.e., 4 to 2 in Figure 1b.1), our central mechanistic hypothesis on achieving oxidative C–C activation was to discover catalytic conditions that allow a direct metal insertion into a C–C bond and a dehydrogenative metal-out process to bring requisite unsaturation in cyclopropanols (Figure 1c, bottom). Specifically, a directed metal insertion into the C–C bond produces a putative metallacyclobutane intermediate I. Because β-H elimination within I is not feasible due to lack of periplanar β-hydrogen and the cyclic nature, regioselective reductive elimination of I affords a sterically hindered alkyl metal species II. The succeeding β-H elimination of II can give cyclic (Z)-metallo enolate–homoenolate equivalent III and M–H. Finally, a labile DG accepts an exogenous nucleophile to remove the DG via the cleavage of an O–DG bond and thus achieve β functionalization (E₁⁺ = DG + Nu in 9). The resulting enolate undergoes normal-polarity α-functionalization with an electrophile (E₂⁺) to give α,β-difunctionalized ketones 9.

DISCUSSION

Reaction Discovery and Optimization Studies.

Significant advancement on carbon-silicon (C–Si) bond formation has been made for production of environmentally sustainable materials and bioactive molecules.^40,41 Despite the importance, a very few catalytic methods have been developed for generally applicable, catalytic silylation by non-polar C–C σ-bond activation.^42–44 To achieve the oxidative C–C activation and silylation of cyclopropanol derivatives, we began our study to find out catalytic conditions to give ketone (Z)-metallo enolate-homoenolate equivalents. Phenyl-substituted cyclopropyl hydrosilyl acetal 12a was first conveniently prepared through Ir-catalyzed hydrosilylation of corresponding cyclopropyl acetate 11a in nearly quantitative yield (Figure 2). A range of monodentate phosphine supporting ligands were examined in the presence of [Rh(nbd)Cl]₂ (nbd: norbornadiene) and norbornene (nbe). After 2.5 h, the C–C silylation reaction produced two pairs of constitutional isomers (13a, 14a, 15a, and 16a), as determined by ¹H NMR spectroscopic and GC–MS spectrometric analyses. Generally, rhodium catalysts assembled with trialkyl phosphines (PR₃) and dialkylmonoaryl phosphines (PArR₂) predominantly effected the redox-neural α-C–C silylation to provide dioxasiline 13a as a major product (only major diastereomer of 13a is shown in Figure 2).⁴⁵ Switching ligands to monoalkyldiaryl phosphines (PAr₂R) and triaryl phosphines (PAr₃) generated more oxidative C–C silylation products, 15a and 16a. Remarkably, the P(4-MeOPh)₃ ligand with rhodium(I) effected a net oxidative C–C activation and β-C–C silylation to provide cyclic β-silyl Z-vinyl acetals, dioxasilepine 16a as a sole product. Interestingly, this result is a complete reversal of our previous report, where highly selective, redox-neutral, α-silylation of cyclopropyl hydrosilyl acetal 12a to afford 13a was achieved under the conditions of Rh(I) and an electron-poor Tp ligand, [Tp(CF₃)²]^–. In this study, the use of electron-donating triaryl phosphine ligand with Rh(I) switched the reactivity pattern to oxidative β-C–C silylation. This exceptional product selectivity eliminates the technical challenge associated with the separation of the four, fairly nonpolar organosilanes with normal phase flash chromatography.

Figure 2.

Reaction optimization study on regio- and stereo-selective and redox-divergent rhodium-catalyzed C–C silylation of cyclopropyl acetates. Yield was determined by ¹H NMR spectroscopy utilizing an internal standard (mesitylene). The major diastereomer of 13a is shown. The diastereomeric ratios of 14a and 15a were not determined. JohnPhos = (2-biphenyl)di-tert-butylphosphine, RuPhos = 2-dicyclohexylphosphino- 2′,6′-diisopropoxybiphenyl, SPhos = 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl, and XPhos = 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl.

The successful oxidative C–C activation requires an effective hydrogen acceptor. We evaluated the capacity of several cyclic hydrogen acceptors. Relatively low-strained cyclic alkenes, for example, cyclohexene [relative ring strain (RRS): 2.5], cycloheptene (RRS: 6.7), and cyclopentene (RRS: 6.8)] gave a mixture of products (13a to 16a) with low yields (Figure 3).⁴⁶ From cyclooctene (RRS: 7.4) to norbornadiene (RRS: 34.7) redox-neutral and oxidative α-C–C silylation products 13a and 15a, respectively, were not produced. Instead, two β-C–C silylation products, 14a (redox-neutral) and 16a (oxidative) were exclusively produced. Norbornene (relative ring strain: 27.2) was identified to be the most effective for the oxidative β-C–C silylation by furnishing 16a in 91% yield. Cyclooctadiene (relative ring strain: 13.3) was comparable to it (16a, 86% yield), yet the redox-neural β-C–C silylation product 14a was produced in 7% yield.

Figure 3.

Evaluation of hydrogen acceptors. Yield was determined by ¹H NMR spectroscopy utilizing an internal standard (mesitylene). The major diastereomer of 13a is shown. The diastereomeric ratios of 14a and 15a were not determined.

With the acetal DG, we noticed that potential competing arene ortho-C–H and cyclopropyl C–H silylations in 12a are feasible.^47–50 In all cases, exceptional chemoselective C–C silylation was exhibited, where the competing cyclopropyl C–H and arene ortho-C–H silylations that give 17a and 18a, respectively, were not observed (Figure 4a). It is attributed to accommodation of a favorable, putative six-membered transition state for C–C activation, leading to 16a rather than adaptation of larger, flexible seven-membered and eight-membered transition states for 17a and 18a, respectively. To further confirm whether the potential competing arene and cyclopropyl C–H activation is feasible or not in the course of the C–C activation, fully deuterated phenyl-substituted cyclopropyl hydrosilyl acetal 12a-D₅ and hydrosilyl acetal 12a-D₄ holding a fully deuterated cyclopropyl moiety were prepared and subjected to the reaction conditions (Figure 4b). Although no protiation in 16a-D₅ was observed, the latter experiment showed minor deuteration in 16a-D₃. Based on the results, we cannot rule out the reversible C–H bond cleavage in this context, as shown in Hartwig’s Rh-catalyzed arene C–H silylation reactions.^51–53

Figure 4.

Chemoselectivity challenges: C–H vs C–C silylation.

Mechanistic Studies and Proposed Catalytic Cycles.

To gain a better understanding of the factors that result in a high level of regio- and chemo-selective C–C activation and silylation, we conducted a series of mechanistic experiments. First, the kinetic isotope effect (KIE) experiment with 12a-H₄ and 12a-D₄ showed inverse secondary KIEs (Figure 5a). Second, the Hammett studies concerning the linear free-energy relationship of the C–C silylation showed that the rate acceleration with electron-withdrawing groups was perceived (Figure 5b). Specifically, the ρ value of 0.95 from this experiment suggests that in the transition state of the C–C cleavage step, the electron density is not significantly built up and the intramolecular donor–acceptor interaction via the Rh-π coordination between a rhodium center and a neighboring π bond is not the turnover-determining step. Together, these KIE and Hammett studies suggest that the C–C cleavage is likely the turnover-determining step.

Figure 5.

Preliminary mechanistic studies for net oxidative C–C silylation of cyclopropyl acetates.

To directly identify reaction intermediates and gain insights into the catalytic oxidative C–C activation reaction, ¹H and ³¹P NMR spectroscopic studies on the reaction of RhCl[P(4-MeOPh)₃]₃ with cyclopropyl hydrosilyl acetal 12a in the presence of norbornene were performed. On stirring the reaction at room temperature for 15 min, the ³¹P NMR spectrum showed two doublet of doublets at 35.1 (dd, J_Rh–P = 114 Hz and J_P–P = 13.2 Hz) and 34.1 ppm (dd, J_Rh–P = 114 Hz and J_P–P = 13.9 Hz), suggesting that the Rh complex holds two nonequivalent phosphines. In the ¹H NMR spectrum, a doublet of doublet of doublets (ddd, J_Rh–H = 24.2 Hz, J_P–H = 14.9 Hz, and J_P–H = 14.9 Hz) was observed at −14.8 ppm. This indicates that the Rh complex holds a metal hydride, coupled to rhodium and two nonequivalent phosphorus atoms, and the hydride is in a cis orientation to the two phosphorus atoms.⁵⁴ Upon warming the reaction at 100 °C for 12 h, the hydride peak in the ¹H NMR spectrum and two nonequivalent phosphorus resonances 35.1 and 34.1 in the ³¹P NMR spectrum disappeared. In the ³¹P NMR spectrum, the major resonance observed was a doublet at 26.7 ppm (d, J_Rh–P = 168 Hz). These observations and literature precedents led us to hypothesize that the Rh hydride species holding two phosphine ligands is likely a resting state of the rhodium catalyst and the doubly phosphine-coordinated Rh(I) silyl species would be the major species after all the substrate is consumed.⁵³

Based on our preliminary mechanistic studies and observations, the plausible mechanism accounting for formation of two net oxidation products, dioxasilepines 16 and its constitutional isomer 15 and two redox-neutral counterparts 13 and 14, through C–C silylation of cyclopropyl hydrosilyl acetals is depicted in Figure 6. The requisite intermediate Rh^I– H B for the oxidative addition of a C–C bond to the rhodium center is generated in two organometallic steps:oxidative addition of hydrosilyl acetals 12 to the Wilkinson-type precatalyst P(4-MeOPh)₃ generates Rh^III–silyl hydride A and a subsequence of reductive elimination of Si and Cl gives B and chlorosilane C.^53,55–59 Then, a three-step sequence involving olefin migratory insertion (to D), oxidative addition of 12 (to D), and reductive elimination produces F and norbornane (detected in ¹H NMR spectroscopy). In the presence of norbornene, the norbornene-bound Rh(I) species G can be formed reversibly from F. The adjacent π donor is indispensable for the C–C metal insertion to provide a putative [6,4]-bicyclic fused rhodacyclobutane intermediate H; alkyl-substituted cyclopropyl hydrosilyl acetals lacking a π donor were not able to undergo the C–C silylation, recovering the starting material cleanly. The rhodium-π interaction is the key to the successful C–C silylation, presumably by developing productive Rh–(C–C) agostic interaction in F.^13,60 Then, the reductive elimination of Si and less hindered carbon centers [e.g., C(β)] in H gives the alkylrhodium species I (β-silylation). For a catalyst turn-over, I bearing an electron-rich rhodium coordinated with a more dissociable, monodentate phosphine ligand undergoes β-H elimination to produce 16 and regenerate Rh^I–H B. σ-Bond metathesis of I with 12 can give the redox-neutral dioxasilepane 14 as a minor product. In the context of formation of their constitutional isomers [e.g., α-silylation products, 13 (redox-neutral) and 15 (net oxidative)], the intermediate H undergoes competing reductive elimination of Si and more hindered carbon centers [e.g., C(α)] to give the alkyl rhodium species J. Then, either σ-bond metathesis of J with 12 or β-H elimination of J provides 13 and 15, respectively.

Figure 6.

Proposed mechanism of net oxidative β-C–C silylation of cyclopropyl hydrosilyl acetals accounting for formation of dioxasilepines 16. Its constitutional isomer 15 and two redox-neutral counterparts 13 and 14 can be formed from a common intermediate H.

Scope of Net Oxidative C–C Silylation.

In light of these mechanistic insights, we investigated the scope of the net oxidative C–C silylation under the catalytic system of the Wilkinson-type catalyst, ClRhP(4-MeOPh)₃. We first investigated the impact of hydrosilyl acetals 1 driven from cyclopropyl acetates 11 on the C–C silylation. Sterically varied dialkyl-substituted dihydrosilanes [H₂SiEt₂, H₂Si(oct)₂, and H₂SiⁱPr₂] gave 16a, 16b, and 16c, respectively, in moderate to excellent yields (Table 1a). Specifically, the Ir-catalyzed ester hydrosilylation of 11 with these silanes generally delivers the corresponding hydrosilyl acetals in nearly quantitative yields. However, net oxidative C–C silylation with sterically demanding dioctyldihydrosilane and diisopropyldihydrosilane affords 16b and 16c in moderate yields. Diphenyl dihydrosilane also underwent sequential Ir and Rh catalysis to provide 16d in 73% yield. Next, we examined C–C silylation by varying the ester substituents. Ir-catalyzed ester hydrosilylation of sterically and electronically differentiated cyclopropyl acetates (11a and 11e–11g) afforded hydrosilyl acetals (16a and 16e–16g), respectively (Table 1b). As demonstrated in our previous traceless acetal-directed arene C–H silylation,^58,59 sterically less encumbered esters (11a and 11e) underwent the net oxidative C–C silylation (90 and 78%) efficiently. Sterically tuned ester (11f) and electronically tuned, α-chloro-substituted ester (11g) exhibited significantly slower kinetics of hydrosilylation (12 h), but the C–C silylation of the two hydrosilyl acetals showed comparable rates with the substrates (11a and 11e) (ca. 2.5 h) in respectable yields.

Table 1.

Scope of Dihydrosilane and Acetal DG^a

^aConditions: 11 (0.2 mmol), rt. Yields are for isolated material over a single-pot, two-step sequence from 11 (16b, 16c, and 16d were isolated by treatment with MeLi).

^b11 (0.2 mmol), 70 °C, and 6 h.

We finally examined the scope of aryl-substituted cyclpropyl acetates (Table 2). A range of substrates 11 were converted to the corresponding dioxasilepines 16 with moderate to excellent yield (52–91%). The product selectivity of the reaction was exceptional and a high level of chemoselectivity was achieved (no arene and cyclopropyl C_sp2–H silylation). The sterically hindered ortho-substituted substrate 11h required an extended reaction time (48 h), to be fully transformed to 16h. However, aryl-substituted cyclopropyl acetates bearing the meta- or para-substituent generally furnished 16i–16s within 2.5 h. Although disubstituted substrates readily participated in the catalytic C–C silylation to deliver 16t and 16u, in the case of 3,4-methylenedioxybenzene-substituted cyclopropyl acetates 11t, we note that it was crucial to use a slight excess of the Rh catalyst (1.2 mol %). Relatively good functional group tolerance was observed, including boronic ester (16j), amine (16k), ethers (16m–16o), trifluoromethyl (16p), halides (16q, 16r), alkene (16s), acetal (16t), 3,5-dimethyl (16u), naphthalene (16v), furan (16w), and indole (16x). Substrates having a substituent in the cyclopropyl ring did not afford 16, and cyclopropyl hydrosilyl acetal was cleanly recovered. It is attributed to steric encumbrance between an incoming catalyst architecture and a substituent in the ring. Under the forcing conditions (>140 °C), α-silylation adduct 13 was observed with ca. 10% yield, instead of 16 (0% yield). This indicates that the added steric hindrance changes the course of the reaction, where the rhodacyclobutane intermediates would rather undergo reductive elimination to give 13 via J (see Figure 6). Finally, to identify whether this catalytic net oxidative β-C–C silylation process would be applicable to the late-stage modification of bioactive molecules to prepare their biologically relevant analogues, cyclopropyl acetates derived from δ-tocopherol (vitamin E), tyrosine (amino alcohol), D-galactose (carbohydrate), geraniol (terpenoid), and estradiol (steroid) were subjected to the reaction conditions. Gratifyingly, these reactions afforded the corresponding dioxasilepines (16y-16ac) with moderate to good yields and exclusive β-regioselectivity and good functional group tolerance.

Table 2.

Scope of Net Oxidative β-C–C Silylation of Cyclopropyl acetates^a

^aConditions: cyclopropyl acetates 11 (0.2 mmol), [Ir(coe)₂Cl]₂ (0.1 mol %), H₂SiEt₂ (3 equiv), THF (0.33 M), room temperature (12 h) or 70 °C (2 h); [Rh(nbd)Cl]₂ (0.8 mol %), P(4-OMePh)₃ (4.8 mol %), norbornene (2 equiv), THF (0.33 M), 100 °C. Yields are for isolated material over a single-pot, two-step sequence from 11. Inseparable siloxane impurities are present in cases where the purity was not high.

^b1 mmol of 11a was used.

^c48 h for the Rh-catalyzed oxidative C–C silylation step.

^d[Rh(nbd)Cl]₂ (1.2 mol %) and P(4-OMePh)₃ (7.2 mol %).

^eIsolated as the adduct of 16x (β-silyl ketone) with MeLi due to the instability of 16x in column chromatography.

Synthetic Applications of Dioxasilepines.

Structurally, dioxasilepines 16 formed from the oxidative C–C activation and silylation of cyclopropyl acetate are constituted by two interconnected groups, a β-silyloxy moiety and Z-vinyl acetal. They can generally serve as stable and chromatographically isolable β-silyl enolate equivalents. Conceptually, a silaphile (SP) activation of the silicon center in 16 can (i) introduce a variety of new functional groups to the silicon moiety, (ii) remove the acetal DG, and (iii) give an opportunity to access α,β-difunctionalized ketones (Figure 7a). Mechanistically, upon addition of a SP to 16, a putative, penta-coordinated silicon species 17 can be formed. This triggers irreversible ring opening of the activated, cyclic vinyl acetal intermediate 17 to give functionalized β-silyl enolate 18 and aldehyde.^58,61,62 Addition of an electrophile to 18 affords α,β-difunctionalized ketones 19. This approach is particularly notable because diversely functionalized β-silyl ketones with a variation of the silyl group can be prepared with ease through post-introduction of an array of new substituents to the silyl moiety. This feature would substantially improve the scope of organosilanes, as opposed to a limited scope found in many silylation chemistry studies.^45,58 We first demonstrated this strategy outlined above with two SPs; upon treatment of 16a with MeLi and lithium acetylide, followed by acidic workup, β-silyl ketones 19a and 19b were produced in good yields, respectively (Figure 7b). Furthermore, the SP addition reaction with estrone-derived dioxasilepine 16ac afforded β-silyl ketones 19c (71% yield). Finally, we demonstrated the oxidative C–C activation, followed by SP-promoted α,β-difunctionalization of cyclopropanols, depicted in Figure 7c. A SP activation of dioxasilepine 16a with MeLi, followed by Pd-catalyzed α-arylation provided α-aryl,β-silyl ketone 20 in 89% yield. Furthermore, a single-pot, SP-promoted, α-fluorination with NFSI and α-alkylation with benzyl iodide led to the generation of α-fluoro,β-silyl ketone 21 (83% yield) and α-benzyl,β-silyl ketones 22 (73% yield), respectively.

Figure 7.

SP activation of dioxasilepines 16: synthesis of β-silyl ketones and α,β-difunctionalized ketones.

The interconnected β-silyl moiety and Z-vinyl acetal in dioxasilepine 16 can be independently oxidized to produce useful synthetic building blocks. To demonstrate this aspect, two oxidative transformations of dioxasilepine 16a were carried out (Figure 8). First, as a silyl moiety can generally serve as a hydroxy equivalent, desilylative oxidation of 16a gave β-hydroxy ketone 23 (86% yield). Second, oxidation of the Z-vinyl acetal with dimethyldioxirane afforded a hydroxy epoxide intermediate, and a subsequent twofold MeLi addition produced silyl 1,2-diol 24 (77% yield, 6:1 dr, a major diastereomer was isolated).

Figure 8.

Oxidative transformations of dioxasilepines 16.

The click chemistry, copper-catalyzed azide–alkyne cyclo-addition (CuAAC) has been a valuable tool for efficient bioconjugation of small molecular spectroscopic probes to a wide range of biomolecular targets.^63–65 Stable and environmentally benign organosilanes make them suitable for their biological application, particularly toward the bioconjugation chemistry. For example, post-modification of dioxasilepines 16 via addition of lithium acetylide to a β-silyl moiety permitted to access β-alkynylsilyl ketone 25 efficiently. Then, CuACC between 25 and an azide-tagged fluorophore (i.e., biotin-N₃) afforded triazole 26 in a good yield (86%) (Figure 9).

Figure 9.

Cu-catalyzed azide–alkyne cycloaddition of β-alkynylsilyl ketone and biotin-N₃.

CONCLUSIONS

We have performed catalytic, net oxidative C–C activation and silylation of cyclopropanols with traceless acetal DG to generate a new class of seven-membered silicon-containing heterocycles, dioxasilepine. This stable and chromatographically isolable, metallo enolate–homoenolate equivalent uniquely holds an interconnected β-silyl moiety and Z-vinyl acetal. Use of an electron-rich Wilkinson-type catalyst with norbornene effected regio- and chemo-selective metal insertion to a C–C bond in a cyclopropane ring, followed by β-hydride elimination. Scope of dihydrosilanes, acetal DGs, and cyclopropyl acetates has been established. This includes several late-stage, net oxidative C–C silylation reactions of biologically relevant molecules. The versatility of dioxasilepines as ketone α,β-dianion equivalents was demonstrated to yield a range of α,β-difunctionalized ketones and diols, harnessing several useful normal-polarity α-functionalization reactions and oxidative transformations. In addition, an application of dioxasilepines toward bioconjugation chemistry was shown. Finally, preliminary studies to account for an associated mechanism pertaining to the oxidative C–C activation suggest that the rhodium-π interaction entails for establishing the Rh–(C–C) agostic interaction and the succeeding C–C cleavage is likely the turnover-determining step. This study underscores the importance of a choice of metal catalysts and an analysis of transition-state geometry for the highly regio- and chemoselective C–C activation.