Chiral Zinc‐Catalyzed Asymmetric α‐Alkylallylation and α‐Chloroallylation of Aldehydes

Abstract

Asymmetric catalysis is now recognized as one of the most efficient methods for the preparation of optically active compounds.[1] Although many catalytic asymmetric reactions have been developed, most reactions are carried out under strictly anhydrous and oxygen-free conditions, because most chiral catalysts and reagents decompose in the presence of even small amounts of water or oxygen. Furthermore, many reactions are conducted at low temperature, such as À78 8C, to obtain high selectivities. It is energy efficient and thus preferable to perform reactions at 0 8C to ambient temperature.Asymmetric allylation of aldehydes provides optically active homoallylic alcohols, which are useful intermediates for the synthesis of natural products, biologically important compounds, and so forth.[2] When substituted allylating reagents are used, it is possible to control the absolute configuration of two successive stereogenic centers during one carbon-carbon bond formation. For catalytic asymmetric allylation of aldehydes (using substoichiometric amounts of chiral sources) allylstannanes [3] and allylsilanes [4] have often been used as allylating reagents.[5] However, allylstannanes are toxic and allylsilanes are less reactive and sometimes have narrow substrate scope. More recently, allylboron reagents have received attention as reactive and less toxic allylating reagents in asymmetric catalysis. [6, 7a-d] However, although allylboron reagents have been successfully used for allylation of less reactive ketones, [6j-l] because of their high reactivity the reactions with aldehydes proceeded instantaneously without catalysts, [7c] and therefore catalytic asymmetric reactions of aldehydes with allylboron reagents have been carried out at low temperature (mostly at À78 8C). Moreover, examples of catalytic asymmetric a-alkylallylation and a-chloroallylation of aldehydes with allylboron reagents to construct two successive stereogenic centers are very rare, and to our knowledge only catalytic asymmetric a-methylallylation (crotylation) using crotylboronates has been reported. [5b,e-i, 6f, 7] Recently, we found that allylation reactions of allylboronates with aldehydes proceed smoothly in the presence of catalytic amounts of Zn(OH) 2 and 2,9-dimethyl-1,10-phenanthroline (dmp) in aqueous media.[8] When a-substituted allylboronates such as 2 a were employed, the a-addition products were obtained exclusively with syn selectivities.As an extension of this work, we have investigated a catalytic asymmetric variant of this reaction. After the investigation of various chiral ligands and allylboronates, it was found that the combination of Zn(OH) 2 and the chiral bipyridine ligand 4[9] with allylboronic acid 2,2-dimethyl-1,3-propanediol ester (2 b) gave the best results. A certain amount of g-adduct was obtained with the allylboronic acid pinacol ester (2 a), whereas in the reaction with 2 b the desired aaddition product was obtained exclusively with excellent syn selectivity and good enantioselectivity (Table 1).Other examples of c...

General Approach to the Synthesis of the Chlorosulfolipids Danicalipin A, Mytilipin A, and Malhamensilipin A in Enantioenriched Form

“…The kinetic resolutions of racemic α,β-dichloroaldehyde (±)- 27 via enantioselective haloallylation with chiral Oehlschlager/Brown haloallylborane reagents ( 33 / 34 ) 10 proceeded with poor enantioselectivity (Scheme 3 a). According to the enantioselective chloroallylation procedure of Kobayashi, 16 the chiral zinc catalyst derived from the bipyridine ligand 38 afforded the product (−)- 35 in moderate enantiopurity, and useful selectivity factors were achieved (Scheme 3 b). However, the resolved starting material, which is always easier to obtain in higher enantiopurity via kinetic resolution, 17 was unstable to the reaction conditions and could not be isolated, leaving only partially resolved product 35 .…”

Iron‐ and Bismuth‐Catalyzed Asymmetric Mukaiyama Aldol Reactions in Aqueous Media

“…The first use of ligand L1 , combined with Sc III as a chiral water‐compatible Lewis acid, in aqueous solvents was reported in 2004 in the asymmetric hydroxymethylation of silicon enolates 20. Since that report, Bi III / L1 ,21, 22 Cu II / L1 ,22, 23 and Zn II / L1 , 22b, 24 systems were shown to be effective chiral Lewis acids for enantioselective hydroxymethylation reactions,20, 21, 25 ring‐opening reactions of meso ‐epoxides,22, 23, 26, 27 Nazarov cyclization reactions,28 and α‐alkyl‐ or α‐chloroallylation reactions of aldehydes24 in aqueous solvents.…”

Zinc Hydroxide‐Catalyzed Asymmetric Allylation of Acetophenones with Amido‐Functionalized Allylboronate in Water

“…Besides indium species, allylboronates can be used for catalytic enantioselective allylation in aqueous media. Kobayashi and his co‐workers realized the relevant reaction of aldehydes by employing chiral zinc catalysis in water‐acetonitrile solution (Scheme b) . They also succeeded the development of an analogous reaction using imino substrates, where chiral allylglycine derivatives were provided with up to 88% ee .…”