The Suzuki–Miyaura cross-coupling is one of the most often utilized reactions in the synthesis of pharmaceutical compounds and conjugated materials. In its most common form, the reaction joins two sp2-functionalized carbon atoms to make a biaryl or diene/polyene unit. These substructures are widely found in natural products and small molecules and thus the Suzuki–Miyaura cross-coupling has been proposed as the key reaction for the automated assembly of such molecules, using protecting group chemistry to affect iterative coupling. We present herein, a significant advance in this approach, in which multiply functionalized cross-coupling partners can be employed in iterative coupling without the use of protecting groups. To accomplish this, the orthogonal reactivity of different boron substituents towards the boron-to-palladium transmetalation reaction is exploited. The approach is illustrated in the preparation of chiral enantioenriched compounds, which are known to be privileged structures in active pharmaceutical compounds.

An original­ syn: The first enantioselective Suzuki–Miyaura cross‐coupling of chiral, enantioenriched secondary allylic boronic esters is described (see scheme; DME=dimethoxyethane, Bpin = pinacolboryl, dba = dibenzylideneacetone). Mechanistic studies show that the reactions proceed via γ‐selective transmetalation followed by reductive elimination. The reaction provides the first independent confirmation that the transmetalation of boronic esters proceeds via a syn pathway.

Palladium-catalyzed cross-coupling reactions of secondary allylic boronic esters with iodoarenes were demonstrated under the conditions previously described for the coupling of benzylic substrates. The regioselectivity of the process was largely dictated by the pattern of olefin substitution.

The catalytic oxidative desymmetrization of meso-diols was realized using a chiral iridium catalyst. In particular, the reaction is effective for the cyclic diols to give the corresponding hydroxy ketones in high chemical yields with high ee's. With this reaction as a key step, a short-step synthesis of common intermediate of ottelione and scyphostatin was achieved.

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Asymmetric tandem coupling of meso-diols with aldehydes was achieved by using a chiral iridium catalyst. This tandem reaction consists of oxidative desymmetrization of the meso-diol, aldol condensation with an aldehyde, and reduction of the enone intermediate. A one-pot method using an excess of a hydrogen donor gave α-benzyl-β-hydroxyindan-1-ones in up to 94% ee and 88% yield. An asymmetric hydrogen autotransfer method in the absence of an additional hydrogen donor gave the desired benzyl ketone in 92% ee.The development of enantioselective tandem reactions is among the most challenging goals of modern synthetic organic chemistry. Sequential processes involving multiple catalysts might be used to convert simple compounds into complex molecules without the need for isolation and purification of intermediates. Although several pioneering works have been reported, the number of asymmetric multicatalytic reactions is limited. 1 We recently reported an oxidative desymmetrization of meso-diols by using a chiral iridium catalyst, 2 and we applied this reaction in a synthesis of otteliones, which are tubulin polymerization inhibitors. 3 Here we describe the use of an iridium catalyst and a base catalyst as a dual-catalyst system to promote several transformations including oxidation, aldol condensation, and 1,4-reduction.Our key strategy is based on the oxidative desymmetrization of a meso-diol by using a chiral iridium catalyst (Scheme 1). General base-catalyzed aldol condensation should then proceed in a stereoselective manner to give an enone intermediate that undergoes 1,4-reduction to give an α-alkyl hydroxy ketone. In our previous oxidative desymmetrization, we used cyclohexanone as an oxidant. This time, we planned to use aldehydes, not only as aldol substrates, but also as oxidants, because their oxidation potential is greater than that of cyclohexanone. A mixture of meso-indane-1,3-diol (1) and benzaldehyde (2a) together with (η 5 -pentamethylcyclopentadienyl)[(1R,2R)-N-tosyl-1,2-diphenyl-1,2-ethanediamine]iridium {Cp*[(R,R)-Tsdpen]Ir; 6} 4 (10 mol%), and KOH (50 mol%) in 1,4-dioxane was stirred at 50°C for 30 minutes. Propan-2-ol was then added, and the mixture was kept for another 30 minutes to give (2S,3S)-2-benzyl-3-hydroxyindan-1-one (5a) 5 in 80% yield and 92% ee as a single diastereomer (Table 1, entry 1). The reaction of 4-fluorobenzaldehyde gave the corresponding fluorobenzyl product 5b in 88% yield and 94% ee. The reaction of 1 with aromatic aldehydes 2c and 2d bearing electron-donating substituents gave unsatisfactory results under these conditions. However, the use of a primary alcohol, such as ethanol or methanol, gave the desired products 5c and 5d in moderate yields (entries 3 and 4). Scheme 1 Tandem oxidation-aldol condensation-conjugate reduction reactionNext, we examined the course of the reaction of 1 with 2a by means of in situ IR spectroscopy. The spectra for a sample reaction in which three equivalents of 2a were added to a premixed solution of one equivalent of 1, 10 mol% of catalyst 6, ...

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A facile and environmentally friendly methodology for ring opening of epoxides with anilines has been developed in the presence of catalytic amounts of bismuth (III) triflate or bismuth (III) trifluoroacetate using microwave-assisted heating. The ease of this procedure allowed preparation of the β-aminoalcohols quickly and efficiently.