No abstract

A highly diastereoselective methodology for the preparation of various substituted piperidines via Negishi cross-couplings with (hetero)aryl iodides was developed. Depending on the position of the C-Zn bond relative to the nitrogen (position 2 vs position 4), the stereoselectivity of the coupling can be directed toward either the trans- or cis-2,4-disubstituted products. Density functional theory calculations on the relative stabilities of the Zn and Pd intermediates were performed to explain the high diastereoselectivities obtained. A novel 1,2-migration of Pd further expands this method to the stereoselective preparation of 5-aryl-2,5-disubstituted piperidines.

Highly regioselective and efficient borylation of a variety of porphyrins has been achieved by reaction with bis(pinacolato)diboron through C-H bond activation under iridium catalysis on the basis of the synthetic protocol developed by Miyaura, Hartwig, and Smith. A boryl group can be selectively introduced at sterically uncongested positions in the peripheral aryl groups of porphyrin substrates whose peripheral beta-positions are sterically hindered. Curiously, beta substituents adjacent to the aryl group to be borylated have unexpectedly large effects on the regioselectivity, because the iridium catalyst can discriminate between subtle steric differences. Chemoselective borylation was also achieved for several functionalized porphyrins. This borylation protocol can be applied to various monomeric and oligomeric functional porphyrins, hence offering an efficient route to elaborate multiporphyrin-based molecular constructs.

Asymmetric 1,3-rearrangement of an alkynyl group of alkynyl alkenyl carbinols giving β-alkynylketones took place in high yields with high enantioselectivity in the presence of a hydroxyrhodium/(R)-binap catalyst. The present method including a key β-alkynyl elimination step in the catalytic cycle is synthetically equivalent to the asymmetric conjugate addition of terminal alkynes to β-substituted enones.

Transition-metal-catalyzed [5+2] cycloaddition of vinylcyclopropanes with carbon À carbon unsaturated bonds is an efficient way of constructing seven-membered carbocycles. Several transition metals such as rhodium, [1] ruthenium, [2] nickel, [3] and iron [4] can catalyze these reactions with alkynes as the reaction partner, and alkenes [1c, 5] and allenes [6] can also be employed under rhodium catalysis. [7,8] Unfortunately, however, the development of asymmetric variants of this useful transformation has not met much success so far. In fact, to the best of our knowledge, only a recent report by Wender addressed this issue, achieving high enantioselectivity for several alkene-tethered vinylcyclopropanes using a cationic Rh/(R)-binap catalyst. [9] For cycloaddition of alkyne-vinylcyclopropanes, in contrast, there is no effective catalytic asymmetric method available to date.[10] Herein we describe the development of such an asymmetric catalysis by the use of a rhodium complex coordinated with chiral phosphoramidite ligand, achieving very high enantiomeric excesses (up to > 99.5 % ee).Initially, we employed alkyne-vinylcyclopropane 1 a as a model substrate and attempted a cycloaddition reaction in the presence of 5 mol % of a cationic Rh/(R)-binap [11] complex in dichloromethane at 30 8C (Table 1, entry 1). Under these conditions, 37 % yield of cycloadduct 2 a was obtained after 5 h with moderate ee value of 64 %. The use of other axially chiral bisphosphine ligands such as (R)-segphos [12] and (R)-H 8 -binap [13] resulted in lower yields and enantioselectivity under otherwise the same conditions (18-29 % yield, 46-55 % ee; entries 2 and 3). In contrast, chiral phosphoramidite ligand (S,S,S)-3 [14] (1.5 equiv to Rh) induced somewhat better enantioselectivity (75 % ee; entry 4) and its diastereomeric ligand (S,R,R)-3 [14,15] dramatically improved both reactivity and stereoselectivity, giving product 2 a in 88 % yield with as high as 99 % ee (entry 5). The absolute configuration of 2 a thus obtained was determined to be (R) by X-ray crystallographic analysis as shown in Figure 1. [16] The scope of the present catalysis using ligand (S,R,R)-3 is illustrated in Table 2. Not only aryl groups (1 a-c) but also alkyl groups (1 d and 1 e) are well tolerated as the substituent on the alkyne, leading to the corresponding cycloadducts 2 with uniformly high yield and excellent enantioselectivity (87-90 % yield, ! 94 % ee; entries 1-6), and the amount of ligand (S,R,R)-3 can be reduced to 6 mol % (1.2 equiv to Rh) as shown in entry 2. High enantioselectivity is also achieved with substrate 1 f having a terminal alkyne, although [a]

In addition: A copper/N‐heterocyclic carbene(NHC)‐catalyzed 1,4‐addition of organoboronates to alkylidene cyanoacetates was developed, in which the catalytic cycle is proposed to consist of a transmetalation/insertion/ligand exchange. An effective asymmetric variant has also been achieved by the use of a chiral NHC ligand (see scheme).

A copper-catalyzed addition of arylboronates to isatins has been developed to give 3-aryl-3-hydroxy-2-oxindoles under mild conditions. The catalytic cycle of this process has been examined through a series of stoichiometric reactions and an effective asymmetric variant has also been described by the use of a chiral N-heterocyclic carbene ligand.

A copper-catalyzed asymmetric allylic substitution of γ,γ-disubstituted allyl phosphates with arylboronates has been developed for the construction of quaternary stereocenters. High regio- and enantioselectivities have been achieved by employing a hydroxy-bearing chiral N-heterocyclic carbene ligand, and both E and Z substrates provide the same enantiomer as the major product. The mechanistic aspect of this catalysis has also been investigated to find that a 1:1 copper/ligand complex is most likely responsible for the present asymmetric catalysis, and the reaction proceeds with almost perfect 1,3-anti stereochemistry with respect to the allylic electrophile.