Tf2NH, an organic acid, efficiently catalyzes (2 + 2) cycloaddition reactions of silyl enol ethers with acrylates or propiolate. The process affords highly substituted cyclobutanes in high yield with high stereoselectivity under practical and environmentally benign conditions. Application for the formation of terpene skeletons and multigram synthesis of four-membered carbocycles were demonstrated.

An efficient catalytic (2 + 2)-cycloaddition reaction leading to the formation of cyclobutane rings has been devised. The process transforms silyl enol ethers and alpha,beta-unsaturated esters into polysubstituted cyclobutanes with a high degree of trans-stereoselectivity. Both the rate and stereoselectivity of the process can be controlled by the choice of the ester group and silyl substituents. The results of stereochemical studies show that the cycloaddition step in this reaction proceeds in a nonstereospecific manner and, thus, by a pathway involving sequential nucleophilic additions via a short-lived zwitterionic intermediate.

A novel chiral aryldichloroborane catalyst bearing binaphthyl skeletons with axial chirality was developed as an asymmetric catalyst for the Diels-Alder reaction of dienes and α,β-unsaturated esters, and could be reused as the corresponding boronic acid. In addition, a new convenient method for preparing arylboronic acids from aryl alcohols is described.Spectacular advances have been achieved in recent years in the enantioselective Diels-Alder reaction of dienes and α,β-unsaturated aldehydes catalyzed by chiral Lewis acids. 1,2 However, there has been relatively less progress in the development of asymmetric catalysts for the reaction with α,β-unsaturated esters as dienophiles because of their low reactivities. 3,4 Alkyldihaloborane is one of the most powerful Lewis acids which can catalyze the latter reaction. 3c,d For example, Hawkins and co-workers previously reported an effective chiral alkyldicholoroborane catalyst prepared by hydroboration of 1-(1-naphthyl)cyclohexene for the latter reaction, which gave high enantioselectivity. 3d However, in general, since alkyldichloroboranes readily decompose to alkanes or alkenes by protonolysis or β-hydride elimination, it is difficult to recover them as alkylboronic acids quantitatively. 5 In addition, in the preparation of optically active alkyldihaloboranes, optical resolution or asymmetric hydroboration is required since they involve chiral carbons adjacent to boron. 3c,d,5 Thus, the utility of chiral alkyldichloroboranes as strong Lewis acid catalysts in enantioselective synthesis encouraged us to seek new members of this class which would not have the disadvantages mentioned above. This paper describes novel and practical chiral aryldichloroborane catalysts 7a-c bearing binaphthyl skeletons with axial chirality which can be reused as the corresponding boronic acids 5a-c. 6 For the synthesis of optically pure 2-dihydroxyboryl-1,1'-binaphthyl (5a), (R)-1,1'-bi-2-naphthol (1a) was first treated with Nphenyltrifluoromethanesulfonimide and the resulting monotriflate 2a was subjected to hydrogenolysis to give mono-ol 3a (Scheme 1). 7 After transformation of the phenolic hydroxyl group to a diethylphosphate, 4a was treated with lithium-naphthalene and trimethylborate successively to give binaphthylboronic acid 5a. 8 As far as we know, this is a new method for preparing arylboronic acid from aryl alcohol. 9 Unfortunately, slight epimerization of 5a was revealed by conversion to the (2R,4R)-2,4-pentanediol ester and 1 H NMR analysis or by conversion to the pinacol ester and HPLC analysis. Therefore, boronic acid 5a was esterified with diethanolamine in 2-propanol, from which the boronate ester 6a was crystallized in good yield. Recrystallization of 6a and subsequent hydrolysis with dilute acid readily provided enantiomerically pure (R)-5a. (R)-6,6'-Diarylbinaphthylboronic acids 5b 8 and 5c 8 were synthesized from 1b and 1c, respectively, in a similar manner.To activate chiral arylboronic acids 5a-c as Lewis acid catalysts, conversion to the corresponding aryldichloroboran...

A versatile method for stereoselective formation of multisubstituted bicyclo[4.2.0]octane framework has been developed by means of catalytic (4 + 2)-(2 + 2) cycloaddition reactions. Its application to the synthesis of a substance reported to be the cytotoxic sesquiterpene, paesslerin A, is described, and it has been made clear that a revision of the structure of natural paesslerin A is required.

No abstract

Chiral dialuminum and trialuminum Lewis acids, which are effective as asymmetric Diels−Alder catalysts, have been prepared from organoaluminum reagents and optically pure binaphthol derivatives.The development of chiral acid catalysts for enantioface discriminating reactions of carbonyl compounds has been one of the most gratifying advances in synthetic chemistry. 1 Although most of them are simple mononuclear Lewis acids, Brønsted acid-assisted chiral Lewis acids (BLAs) 2 and multinuclear chiral Lewis acids 3 have recently been reported. Well-designed multinuclear acids enhance the efficiency of the electrophilic activation and enantioface discrimination of carbonyl groups toward nucleophilic addition. These features have prompted chemists to design and synthesize a broad range of multinuclear chiral acids that differ with regard to the number, orientation, and nature of electrophilic sites. 4 There are two types, 2a and 2b, of electrophilic activation of carbonyl compounds with dinuclear chiral Lewis acid 1 prepared from metal compounds (2 equiv) and (R)-binaphthol (1 equiv) (Scheme 1): an adjacent electrophilic site in 2a is bridged by an alkoxy oxygen, while an adjacent electrophilic site in 2b is bridged by X (alkyl groups, alkoxy groups, halides, etc.). These Lewis acids which activate carbonyl compounds via 2a or 2b can be regarded as Lewis acid-assisted chiral Lewis acids, which use a Lewis acid instead of the Brønsted acid in chiral BLA. In this paper, we describe our efforts to design multinuclear organoaluminum complexes with (R)-binaphthol derivatives.Chiral dialuminum compound 4 was quantitatively prepared from (R)-3,3'-bis(triphenylsilyl)binaphthol (3, 1 equiv) and diisobutylaluminum hydride (DIBAH, 2 equiv) in dichloromethane at room temperature (Scheme 2). Surprisingly, 4 was generated with 50% conversion even when DIBAH (1 equiv) was added to 3 (1 equiv). The asymmetric structure of 4 was assigned by 1 H and 13 C NMR spectral analyses (Table 1) and the measurement of hydrogen gas evolved. In a similar manner, chiral dialuminum compound 6, which has a symmetric structure, was also prepared from 3 (1 equiv) and trimethylaluminum (2 equiv) (Scheme 2). 5 However, when trimethylaluminum (1 equiv) was used, BLA-type 5 was generated quantitatively.

A multicomponent domino reaction involving three mechanistically distinct Tf2NH-catalyzed reactions was developed. The reaction cascade enables the assembly of a skewed 5/6/4 tricyclic motif with migration of the reactive site with the assistance of a catalyst. The tricyclic product was used to achieve the first total synthesis of cytotoxic paesslerin A by regioselective C–H insertion of the sulfonyl carbenoid and base-promoted olefin isomerization. Our results led to the revision of the originally proposed tricyclic structure of paesslerin A.

A novel and efficient method for the Cr(II)-mediated desulfonylation of α-sulfonyl ketone by a Cr-ligand-Mn system has been developed during the course of process research on Halaven (eribulin mesylate). This reaction is dramatically accelerated in the presence of an appropriate bipyridyl-type ligand. This system is applicable to reduction of α-sulfur-substituted ketones. In addition, a Cr-Cp2ZrCl2-Mn catalytic system is also applicable to desulfonylation of α-sulfonyl ketone.