Keishi Takatsu

Rhodium-catalyzed asymmetric [5+2] cycloaddition of alkyne-vinylcyclopropanes.

Transition-metal-catalyzed [5+2] cycloaddition of vinylcyclopropanes with carbon carbon unsaturated bonds is an efficient way of constructing seven-membered carbocycles. Several transition metals such as rhodium, ruthenium, nickel, and iron can catalyze these reactions with alkynes as the reaction partner, and alkenes and allenes can also be employed under rhodium catalysis. 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. For cycloaddition of alkyne–vinylcyclopropanes, in contrast, there is no effective catalytic asymmetric method available to date. 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 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 and (R)-H8-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 (1.5 equiv to Rh) induced somewhat better enantioselectivity (75 % ee ; entry 4) and its diastereomeric ligand (S,R,R)-3 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. 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] Dr. R. Shintani, H. Nakatsu, K. Takatsu, Prof. Dr. T. Hayashi Department of Chemistry, Graduate School of Science Kyoto University, Sakyo, Kyoto 606-8502 (Japan) Fax: (+81) 75-753-3988 E-mail : shintani@kuchem.kyoto-u.ac.jp thayashi@kuchem.kyoto-u.ac.jp Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200901463. Table 1. Ligand effect in the rhodium-catalyzed asymmetric [5+2] cycloaddition of 1 a.

Rhodium-Catalyzed Rearrangement of Aryl Bis(alkynyl) Carbinols to 3-Alkynyl-1-indanones†

A transition-metal-catalyzed isomerization or rearrangement can provide an efficient way to convert readily accessible organic compounds into those with more structural complexity under mild conditions. For example, rhodium-catalyzed isomerization of secondary propargyl alcohols to the corresponding a,b-unsaturated ketones was described, and a reaction pathway involving b-hydrogen elimination of an alkoxorhodium species with subsequent hydrorhodation of an alkyne was proposed (Scheme 1a). This reaction sequence

Rhodium-Catalyzed Kinetic Resolution of Tertiary Homoallyl Alcohols via Stereoselective Carbon−Carbon Bond Cleavage

A nonenzymatic kinetic resolution of tertiary homoallyl alcohols has been developed through a rhodium-catalyzed retro-allylation reaction under simple conditions. Selectivity factors of up to 12 have been achieved by employing (R)-H8-binap as the ligand, and the reaction can be conducted on a preparative scale.

Tuning the Chiral Environment of C2-Symmetric Diene Ligands: Development of 3,7-Disubstituted Bicyclo[3.3.1]nona-2,6-dienes

Through the structural analysis of bicyclo[3.3.1]nona-2,6-dienes, new C(2)-symmetric chiral diene ligands 1 based on 3,7-disubstituted bicyclo[3.3.1]nona-2,6-diene framework have been designed and synthesized. These chiral ligands readily bind to rhodium(I) and provide a different chiral environment from the existing chiral dienes. The rhodium complexes thus obtained act as effective catalysts for 1,4-addition of alkenyl- and arylboronic acids to various alpha,beta-unsaturated ketones, including several combinations that were previously difficult to provide high enantioselectivity.

Synthesis of quaternary carbon stereocenters by copper-catalyzed asymmetric allylic substitution of allyl phosphates with arylboronates.

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.