The synthesis of compounds having quaternary carbon centers through a catalytic stereo- and regioselective difunctionalization of 2-substituted 1,3-dienes remains elusive. Here, we present a dual Co/photoredox-catalyzed cascade approach that addresses this challenge using modular vinyl cyclic carbonates functioning as masked 2-aryl-1,3-diene surrogates. The latter species are conveniently prepared in situ and converted into nucleophilic Co­(allyl) intermediates that are intercepted by aldehydes to afford homoallylic alcohols with ample scope in reaction partners. The developed protocol marks a significant step forward in the use of structurally versatile 1,3-dienes and their catalytic 1,2-hydroalkylation and 1,2-dicarbofunctionalization.

Tertiary allylic alcohols equipped with a carboxyl group can be smoothly aminated under ambient conditions by a conceptually new and stereoselective protocol under palladium catalysis. The in situ formed Z‐configured γ‐amino acid cyclizes to afford an α,β‐unsaturated γ‐lactam, releasing water as the only byproduct. This practical catalytic transformation highlights the use of a carboxyl group acting as an activating and stereodirecting functional group to provide a wide series of pharma‐relevant building blocks. Various control reactions support the crucial role of the carboxyl group in the substrate to mediate these transformations.

a 1a (0.10 mmol), 2a (0.15 mmol), Ir(ppy)2(dtbbpy)PF6 (1.0 mol%), Pd2(dba)3 (2.5 mol%), L* (6.0 mol%), Cs2CO3 (0.10 mmol) were combined in CH3CN (2.0 mL) at 25 °C under blue LED radiation (445 nm, 0.7 A, corresponding to a photon flux of 1.2 µeinstein/s) for 2 h. Yields and b/l ratios were determined by 1 H NMR analysis using CH2Br2 as an internal standard. Enantiomeric ratios (er) were determined by UPC2. b In the absence of Cs2CO3. c In the absence of Ir(ppy)2(dtbbpy)PF6. d In the dark. e In the absence of Cs2CO3, under blue LED radiation (445 nm, 1.0 A, corresponding to a photon flux of 1.6 µeinstein/s).The use of other diphosphine ligands (L9-L15) did not improve the process outcome (entries 9-15). Further variations of the protocol (entries 16-19) were first carried out with (R)-DTBM-SegPhos being cheaper than (R)-3,5-tBu-MeOBIPHEP, but providing nearly the same regio-and enantiocontrol (cf., entries 4 versus 5). In the absence of Cs2CO3, 3aa was obtained in a slightly higher yield and er (entry 16 versus 4), and therefore was omitted for the optimized conditions (vide infra). Omitting the iridium PC (entry 17) gave 3aa in 25% yield suggesting that Hantzsch ester 2a could itself also serve as a photoreductant to form a radical cation that subsequently generates, through homolytic cleavage, the requisite alkyl radical for the CC coupling. 12 As expected, no product was detected without blue LED irradiation, but by further increasing the light intensity, the yield of 3aa increased to 71% (entry 19). With these alternative conditions in hand, we then re-used (R)-3,5-tBu-MeOBIPHEP L5 as ligand, which afforded the product in 75% yield and with an er of 89:11 (entry 20).Scheme 2. Product scope using various VCCs to generate quaternary carbon stereocenters. Reaction conditions: 1 (0.10 mmol), 2a (0.15 mmol), Ir(ppy)2(dtbbpy)PF6 (1.0 mol%), Pd2(dba)3 (2.5 mol%), (R)-3,5-tBu-MeOBIPHEP L5 (6.0 mol%), CH3CN (2 mL), 2 h, blue LED (445 nm, 1 A, corresponding to a photon flux of 1.6 µeinstein/s). Yields of the isolated, column-purified products are reported. The enantiomeric ratios (er values) were determined by UPC2. The b/l ratios were determined by 1 H NMR analysis.With these optimized conditions we then examined the generality of similar substrate combinations providing homoallylic alcohols with quaternary carbon stereocenters (Scheme 2, 3aa-3ja). Variation of the aryl substituents on the VCC in the presence of Hantzsch ester 2a generally provided the homoallylic alcohols with remarkable branch-selectivity (b:l >95:5) and in appreciable isolated yields of up to 78% (3ga). Good enantio-induction levels of up to 89:11 er for the majority of the products were achieved except for 3fa, 3ha and 3ja. Whereas for 3ha the presence of the thiophen-2-yl group could interfere through coordination to Pd(allyl) intermediates, the use of a VCC with an additional substituent (R 1 = Ph, 1j) on the vinyl group hence increasing the steric demand substrate activation was detrimental to both the product yield (33%) and optical purity ...

The challenging metal‐catalyzed asymmetric synthesis of highly functional quaternary carbon centers using decarboxylative C(sp3)−C(sp3) bond formation reactions is reported. The key substrate, a vinyl cyclic carbonate, is activated to provide concomitantly both the requisite nucleophile (by formal umpolung) and electrophile reaction partner preceding the asymmetric cross‐coupling process. A wide screening of reaction conditions, additives and catalyst precursors afforded a protocol that gave access to a series of compounds featuring densely functionalized, elusive quaternary carbon stereocenters in appreciable yield and with enantiomeric ratios (er's) of up to 90 : 10.

Dual palladium/photoredox-catalysis provides an effective method for the asymmetric synthesis of vicinal a,b-tri/tetra- or a,b-tetra-substituted homoallylic alcohols. Regio- and enantioselective decarboxylative allylic alkylation of vinyl cyclic carbonates is reported using Hantzsch type esters as radical precursors. The developed methodology combines the use of versatile and accessible reagents and can be operated under mild reaction conditions giving the target molecules in appreciable to good yields, high branch-selectivity and appreciable enantiomeric ratios of up to 94:6. This protocol marks a rare example of the use of prochiral electrophiles for the creation of vicinal congested carbon centers.