The first enantioselective aldehyde α-benzylation using electron-deficient aryl and heteroaryl substrates has been accomplished. The productive merger of a chiral imidazolidinone organocatalyst and a commercially available iridium photoredox catalyst in the presence of household fluorescent light directly affords the desired homobenzylic stereogenicity in good to excellent yield and enantioselectivity. The utility of this methodology has been demonstrated via rapid access to an enantioen-riched drug target for angiogenesis suppression.The benzylic alkylation of chiral enolates has become a mainstay transformation in chemical synthesis, mainly due to the seminal research efforts of Evans, Oppolzer, Seebach, and Myers.1 Surprisingly, however, catalytic enantioselective variants of this venerable reaction remain confined to a small but valuable group of substrate types. Phase transfer benzylation of glycine-derived imines,2 chiral triamine ligation of ketone-derived lithium enolates,3 and the use of Jacobsen's Cr(salen) complex with preformed stannous enolates4 are among the most successful examples.5 Direct organocatalytic methods to form α-benzylated aldehydes have also been reported wherein the electrophilic partner requires multiple and/or electronrich aryl rings (to enable the intermediate formation of stabilized benzylic carbocations).6 Recently, our laboratory introduced a new mode of activation termed photoredox organocatalysis,7 , 8 the mechanistic foundation of which relies on the propensity of electrophilic radicals (derived from photocatalytic reduction of alkyl halides) to combine with facially biased enamines (derived from aldehydes and a chiral amine catalyst). Inspired by this strategy, we hypothesized that the enantioselective α-benzylation of aldehydes might also be possible via the marriage of these activation pathways. Herein, we present a new direct and enantioselective catalytic protocol for the α-alkylation of aldehydes, a transformation that is successful with a wide array of simple monoaryl9 and monoheteroaryl methylene halides. Design PlanAs detailed in Figure 1, it has been established that commercially available fac-Ir(ppy) 3 (1) (ppy = 2-phenylpyridine), commonly used as a green triplet emitter in OLEDs, can readily accept a photon from weak fluorescent light to generate the strong reductant excited state fac-*Ir(ppy) 3 (2) (E 1/2 = −1.73 V vs saturated calomel electrode (SCE) in CH 3 CN). 10 We hoped that single electron transfer (SET) from fac-*Ir(ppy) 3 to a suitable benzylic bromide might render an aromatic radical anion that would rapidly undergo σ-bond cleavage to afford the bromide anion and an electrophilic benzyl radical 3. Within the same time frame, condensation of an aldehyde substrate with imidazolidinone catalyst 4 should form a highly π-nucleophilic enamine 5 which should then combine with the electron-deficient radical 3 to enantioselectively forge the crucial homobenzylic center. Rapid oxidation of the resultant α-amino radical 11 6 by fac-Ir(ppy) 3 + (7) (E 1/...

Benzothiophene and benzoselenophene analogues of the thiophene-containing antihypertensives milfasartan and eprosartan were prepared and tested for AT(1) receptor antagonist properties. While the sulfur-containing systems were prepared following existing methodology, the selenium-containing analogues required the development of novel, tandem free-radical chemistry involving addition of aryl radicals to alkynes, followed by intramolecular homolytic substitution at the higher heteroatom. All four compounds prepared proved to be excellent AT(1) receptor antagonists, with pK(B) estimates of 7.2-9.5.

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EBC-23 (2), a prostate anticancer agent, was isolated from the fruit of Cinnamomum laubatii (family Lauraceae) in the Australian tropical rainforest. Extensive NOE experiments enabled the relative stereochemistry of the proposed EBC-23 (2) structure to be determined. Total synthesis of both enantiopodes over nine linear steps, involving challenging RCM and spiroacetal cyclizations, confirmed the gross structure and relative and absolute stereochemistry.