New synthetic reactions of allyl alkyl carbonates, allyl .beta.-keto carboxylates, and allyl vinylic carbonates catalyzed by palladium complexes

Abstract

In 1965 we reported that (ir-allyl)palladium chloride reacts with carbonucleophiles such as malonates, acetoacetates, and enamines, thereby offering a new method for carbon-carbon bond formation1,2 (see Scheme I). Later synthetic applications of this reaction have been explored mainly by Trost.3 Certain allylic compounds, such as allylic acetates, react with Pd(0) complexes to form (Tr-allyl)palladium complexes in situ; these, without being isolated, react with carbonucleophiles. On the basis of these reactions, a catalytic allylation of carbonucleophiles with allylic esters has been developed,4,5 and this catalytic process is now widely used for carbon-carbon bond formation in organic synthesis3,6 (see Scheme II). In addition to allylic esters, many other allylic compounds such as allylic ethers, phosphates, amines, nitro compounds, sulfones, and halides can also be used for catalytic allylation in the presence of bases.Thus far, the main synthetic application of (x-allyl)palladium chemistry has been the catalytic allylation of carbonucleophiles using allylic acetates. Recently, however, we have broadened the scope and usefulness of (ir-allyl) palladium chemistry by discovering several new reactions using allyl carbonates and allyl /3-keto carboxylates. We have found that allyl alkyl carbonates 1, allyl /3-keto carboxylates 2, and allyl vinylic carbonates 3 are very reactive substrates and undergo a number of reactions that are difficult to achieve with allylic acetates under mild conditions. These substrates, which react with Pd(0) complexes to form ( -allyl)palladium alkoxides 5 or enolates 12a and 12b after facile decarboxylation, undergo various transformations depending on reaction conditions. The major reactions paths can be summarized in Scheme III. All these reactions proceed with facile decarboxylation. Mechanistically, they are closely related to each other and are discussed from common viewpoints in this Account. Reactions of Allyl Alkyl CarbonatesAllylation reaction of carbonucleophiles with various allylic compounds has now seen widespread use in organic synthesis.3,6 Allylic acetates are mainly used in the presence of bases. Several years ago we and Trost Jiro Tsuji obtained his B.S. from Kyoto University and then came to the U.S., where he obtained his Ph.D. at Columbia working with G. Stork in 1960. After returning to Japan, he worked at Basic Research Laboratories, Toray Industries Inc., and moved In 1974 to Tokyo Institute of Technology as a professor. Development of new reactions catalyzed by transition-metal complexes, particularly palladium complexes, and application of these new catalytic reactions to total synthesis of natural products are his major research programs.

Stereoselective Construction of Quaternary Stereocenters

“…[20] The racemic decarboxylative alkylation of allyl enol carbonates can be traced back to reports of Tsuji in the 1980s. [21] Stoltz and Behenna recently published the first asymmetric version of this Tsuji allylation. [22] The P,N ligand 22 [23] was used for intramolecular conversion of enol carbonate 21 to ketone 23 (Scheme 6).…”

Development of .BETA.-keto ester and malonate chemistry Palladium-catalyzed new reactions of their allylic esters

“…5) Acetoacetates and malonates are important compounds in organic chemistry. They are extensively used in organic synthesis for the preparation of a variety of β-alkylated ketones 9, esters 10, and carboxylic acids 11 via alkylation, hydrolysis, and decarboxylation.…”

“…As summarized in the scheme, six transformations to afford the respective products 21-27 occur under different conditions and depending on the substituents R's. 5) In addition to allyl β-keto carboxylates, other allyl acetates bearing electron-withdrawing groups at α-carbon such as allyl malonates, cyanoacetates, and nitroacetates undergo similar transformations. Each transformation is explained in the followings.…”

Palladium-Catalyzed Allylation of Acidic and Less Nucleophilic Anilines Using Allylic Alcohols Directly

“…[7][8][9][10] The processes have been shown to proceed by attack of nucleophiles on intermediate h 3 -allylpalladium(II) complexes generated by oxidative addition of allylic compounds including halides, [11][12][13] esters, [14][15][16][17][18][19][20][21][22][23][24][25][26] carbonates, [27][28][29][30][31][32][33][34][35][36] carbamates, [37][38][39] phosphates, [40][41][42] and related derivatives [43][44][45][46][47][48][49] to a Pd(0) complex. Because these substrates are synthesized from the corresponding allylic alcohols, palladium-catalyzed conversion of allylic alcohols directly into allylation products are highly desirable, especially from the viewpoint of the atom economy.…”

“…Using cinnamyl alcohol (2b) as allylating agent worked well with acidic and less nucleophilic anilines (entries, 2,5,8,11,13,15). The sterically more demanding 2-cyclohexenol (2c), was an inefficient allylation reagent for 1a and for the more acidic anilines, although at reflux temperature (entries 3,6,9,12,14,16). Reaction of 2c with steric constraints amines 1a-c gave the worst yields.…”