Titanium(IV) Chloride-Catalyzed Photoalkylation via C(sp3)-H Bond Activation of Alkanes.

Despite the sophistication of C-H functionalization as one of the most powerful tools in organic synthesis, methodology for performing hydrogen-atom transfer of unactivated alkanes remains rather scarce. Herein, we describe chlorine radical-catalyzed C(sp3)-H photoalkylation using titanium(IV) chloride via a ligand-to-metal charge transfer process. Enabled by the unique properties of this abundant metal salt, the reaction not only effected the coupling of various alkanes with radical acceptors but also was shown to be applicable to direct photoalkylation of aromatic ketones.

Amine-tethered phenylboronic acid-enabling ring-opening strategy for carbon chain elongation from double aldol cyclic hemiacetals.

The addition of carbon nucleophiles to cyclic hemiacetal forms of double aldols is a promising approach toward the synthesis of structurally attractive 1,3-polyol derivatives. Cyclic hemiacetals are generally unreactive to carbon nucleophiles under neutral conditions, however, because the electrophilic aldehyde function is masked. Here we developed an amine-tethered phenylboronic acid 7g, which transforms double aldol cyclic hemiacetals to ring-opened linear aldehydes. Combined with the previously-developed copper-catalysed asymmetric double aldol reaction (L. Lin, K. Yamamoto, H. Mitsunuma, Y. Kanzaki, S. Matsunaga and M. Kanai, J. Am. Chem. Soc., 2015, 137, 15418), this method produced synthetically useful chiral building blocks containing a 1,3-di- or tri-ol moiety.

Copper(I)-Catalyzed Enantio- and Diastereodivergent Borylative Coupling of Styrenes and Imines.

We report copper(I)-catalyzed enantio- and diastereodivergent borylative coupling of styrenes and imines to produce enantiomerically-enriched α,ß-dibranched γ-boryl amine derivatives. Each of the four possible stereoisomers of the products, derived from the two contiguous stereocenters, was selectively accessible by choosing a proper chiral ligand for the copper catalyst. This method, which combines catalyst-controlled stereodivergency and constitutional divergency derived from the lynchpin motif (i.e., the C-B bond), offers a strategy for addressing the construction of molecular structural diversity concomitant with precise chirality control.

Catalytic Asymmetric Iterative/Domino Aldehyde Cross-Aldol Reactions for the Rapid and Flexible Synthesis of 1,3-Polyols.

We report here catalytic asymmetric iterative and domino cross-aldol reactions between aldehydes, endowed with a high level of robustness, flexibility, and generality. A Cu(I)-DTBM-SEGPHOS complex catalyzes an asymmetric cross-aldol reaction between acceptor aldehydes and boron enolates derived from donor aldehydes, which are generated through Ir-catalyzed isomerization of allyloxyboronates. The unit process can be repeated using the aldol products in turn as acceptor substrates for the subsequent asymmetric aldol reaction. The donor aldehydes and stereoselectivity can be flexibly switched in a stepwise manner for the double-aldol reaction. Furthermore, asymmetric triple- and quadruple-aldol reactions are possible in one-pot using the appropriate amounts of donors and amine additives, rapidly elongating the carbon skeleton with controlling up to eight stereocenters. The method should be useful for straightforward synthesis of enantiomerically and diastereomerically enriched 1,3-polyols.