Search

A new chiral reagent for syn-selective aldol reactions has been developed based on the recent finding that the stereochemistry of the boron-mediated aldol reaction of a carboxylic ester is controlled by the bulkiness of the alcohol moiety of the ester, by the proper choice of reagents, and by the enolization conditions. This readily available, inexpensive reagent has been utilized in studies directed towards the synthesis of the macrolide tedanolide.

New chiral auxiliaries based on the bicyclic-isoxazolidine skeleton, 3-oxa-2,7-diazabicylo[3,3,0]octane derivatives, were synthesized in 60–80% overall yields from amino acids. Asymmetric alkylation and boron aldol reaction using the auxiliaries proceeded with high selectivities. “Carboxylic amide” has been used for the asymmetric boron-mediated aldol reaction for the first time.

Asymmetric alkylation of the potassium enolates derived from N-propionyl benzopyrano-[4,3-c]-isoxazolidine derivatives with chiral alkyl triflates proceeded smoothly with high diastereoselectivity. The stereochemistry of the newly formed stereogenic center was fully controlled by the facial selectivity of the enolate according to the rule of double asymmetric synthesis. The application of this methodology led to the first synthesis of (+)-siphonarienone, a marine polypropionate natural product.

Asymmetric alkylation of the potassium enolates derived from N-propionyl benzopyrano-[4,3-c]-isoxazolidine derivatives with chiral alkyl triflates proceeded smoothly with high diastereoselectivity. The stereochemistry of the newly formed stereogenic center was fully controlled by the facial selectivity of the enolate according to the rule of double asymmetric synthesis. The application of this methodology led to the first synthesis of (+)-siphonarienone, a marine polypropionate natural product.

New chiral auxiliaries based on the bicyclic-isoxazolidine skeleton, 3-oxa-2,7-diazabicylo[3,3,0]octane derivatives, were synthesized in 60–80% overall yields from amino acids. Asymmetric alkylation and boron aldol reaction using the auxiliaries proceeded with high selectivities. “Carboxylic amide” has been used for the asymmetric boron-mediated aldol reaction for the first time.

A new chiral reagent for syn-selective aldol reactions has been developed based on the recent finding that the stereochemistry of the boron-mediated aldol reaction of a carboxylic ester is controlled by the bulkiness of the alcohol moiety of the ester, by the proper choice of reagents, and by the enolization conditions. This readily available, inexpensive reagent has been utilized in studies directed towards the synthesis of the macrolide tedanolide.

Bis-oxazolines (1–7) prepared from diethyl malonate and chiral amino alcohols were converted into their Cu(II) complexes which, upon activation, exhibit high enantioselectivity of up to 99 %ee for catalytic cyclopropanation of olefins.

Boron-mediated aldol reaction of carboxylic esters is described in detail. Contrary to the gener-al belief that carboxylic esters are inert toward the conventional enolization conditions, propionate esters are shqwn to have adequate reactivity on the boron-mediated aldol reaction. More impor-tantly, the stereochemical course of the aldol reaction can be controlled by the judicious choice of the enolization reagents. Complementary anti- and syn-selective asymmetric aldol reaction of structurally related chiral esters are developed. Also, novel double aldol reaction is discovered with acetate esters, which provides a precursor to the synthesis of chiral triols of C3-symmetry. Extensive NMR experiments lead to characterize the first carbon-bound boron enolates and the novel doubly borylate enolates as intermediates of the double aldol reaction. A plausible mecha-nism of the double aldol reaction is proposed.

(2S,3R)-2,4-Dimethyl-1,3-pentanediol R 2(N-Benzyl-N-mesitylenesulfonyl)amino-1-phenyl-1-propyl propionate Is this (+)-1 I (1′R)-Phenyl-(2′S)-[(phenylmethyl)[(2,4,6-trimethylphenyl)sulfonyl]amino-propyl(3R)-hydroxy-(2R),4-dimethylpentanoate 2 R (2S,3R)-2,4-Dimethyl-1,3-pentanediol 3 2-(N-Benzyl-N-mesitylenesulfonyl)amino-1-phenyl-propanol Keywords: stereoselective reactions, enantioselective; stereoselective reactions, diastereoselective; alkylation, C-alkylation (including Aldol, Michael, and Friedel-Crafts reactions); metal-catalyzed reactions (exclusive of reductions); reduction, CO2RCH2OH; alkylation N-alkylation

2-(N-Benzyl-N-mesitylenesulfonyl) amino-1-phenyl-1-propyl propionate R (−)-Norephedrine I 2-(N-mesitylenesulfonyl)amino-1-phenyl-1-propanol 2 2-(N-Benzyl-N-mesitylenesulfonyl)amino-1-phenyl-1-propanol 3 P 2-(N-Benzyl-N-mesitylenesulfonyl)amino-1-phenyl-1-propyl propionate 1 Keywords: sulfur compounds; alcohols and diols, substituted; sulfonation, N-sulfonation; acylation (including formylation and Friedel-Crafts reactions); alcohols and diols, substituted

The boron-mediated aldol reaction of carboxylic esters is described in detail. Contrary to the general belief that carboxylic esters are inert under the condition of the boron enolate formation, propionate esters are enolized with certain combinations of a boron triflate and an amine. More importantly, the stereochemical course of the aldol reaction can be controlled by the judicious selection of the enolization reagents. Treatment of propionate esters with c-Hex2BOTf and triethylamine produces anti-aldol products, and that with Bu2BOTf and diisopropylethylamine gives syn-aldol products selectively after reaction with aldehydes. Complementary anti- and syn-selective asymmetric aldol reactions with structurally related, readily available chiral norephedrine-derived propionate esters are developed.

A new modification of Peterson reaction leading to elongation of three carbon units by treatment of aldehydes with titanium ate complex, prepared from 1-lithio-1-(1-alkoxy)allyltrimethylsilane and titanium(IV) isopropoxide, is described.