Methods and Design in Organic Synthesis

Methods and Design in Organic Synthesis is a one-semester course of the Master in Organic Chemistry at the Universitat de Barcelona. This course introduces the basic concepts of retrosynthetic analysis and covers the most important transformations in Organic Chemistry. The course thus aims to provide a solid knowledge of the main reactions and useful guidelines to design efficient syntheses of organic compounds

Organic Synthesis

Organic Synthesis is a one-semester course of the fourth year of the Chemistry Degree at the Universitat de Barcelona. This course covers the most important transformations in Organic Chemistry, including a short introduction to the Retrosynthetic Analysis. The aim is to provide a solid knowledge of the main reactions and their mechanism, which could later be improved during Master studies

Stereoselective oxidation of titanium(IV) enolates with oxygen

A novel approach to synthesize enantiomerically pure α-hydroxy carboxylic derivatives is reported. A highly stereoselective oxidation of titanium(IV) enolates from chiral N-acyloxazolidinones is performed with oxygen under simple experimental conditions that do not require any reducing steps. The success of this approach depends on the biradical character of titanium(IV) enolates

Stereoselective Acetate Aldol Reactions From Metal Enolates

This review deals with metal enolate-mediated stereoselective acetate aldol reactions. It summarizes recent advances on aldol additions of unsubstituted metal enolates from chiral auxiliaries, stoichiometric and catalytic Lewis acids, or acting in substrate- controlled reactions, which provide stereocontrolled aldol transformations that allow the efficient synthesis of structurally complex natural products

Optimized asymmetric synthesis of umuravumbolide

Herein, the asymmetric synthesis of umuravumbolide (1) is described. The new approach features highly stereoselective transformations (dr ≥ 95:5) to install both stereocenters and the Z olefin, which involve a new radical alkylation, an Ando olefination, and a Krische allylation on a Z allylic alcohol, not reported before. The application of such successful reactions, together with the limited use of protecting groups and concession steps, makes it possible to complete the synthesis in 10 steps, resulting in a 39% overall yield from chiral N-acyl oxazolidinone 2

Stereoselective and catalytic synthesis of anti-β-Alkoxy-α-azido carboxylic derivatives

Direct addition of a chiral N-azidoacetyl thiazolidinethione to a variety of dialkyl acetals catalyzed by a commercially available and structurally simple nickel(II) complex gives access in good yields and a highly stereocontrolled manner to anti-beta-alkoxy-alpha-azido carboxylic derivatives which, in turn, can be easily converted into a wide array of enantiomerically pure compounds

Synthesis and acylation of 1,3-thiazinane-2-thione

1. Procedure (Note 1) A. 3-Ammoniopropylsulfate (1). An oven-dried single-necked 100 mL round-bottomed flask (14/23 joint), equipped with a 2.5-cm Teflon-coated magnetic stirbar, is charged with 3-amino-1-propanol (11.5 mL, 150 mmol, 1 equiv) (Note 2) and anhydrous dichloromethane (35 mL) (Note 3). A 50 mL pressure-equalizing addition funnel (14/23 joint) equipped with a CaCl2 tube is attached to the round-bottomed flask and is then charged with chlorosulfonic acid (10.5 mL, 159 mmol, 1.06 equiv) (Note 4) using a 20 mL glass luer-lock syringe. The flask is immersed in an ice/water bath and the solution is stirred for 5 min. The chlorosulfonic acid is added dropwise over 30 min, allowing the fumes to escape. A white precipitate is formed during the addition. Once the addition is complete, the reaction is stirred at 0 °C for 20 min and left to warm slowly to room temperature over 30 min (Note 5). Once at room temperature, the reaction mixture is stirred for 1 h. The resulting mixture is filtered through a 70 mm diameter Number 3 Glass filter funnel with a Büchner setup. A bent spatula and methanol (25 mL) (Note 6) are used to remove remaining product from the flask walls. The mixture in the filter funnel is triturated with methanol (40 mL, then 2 × 20 mL) (Note 6), using a spatula to break up the lumps each time. The resulting white solid is broken up into a coarse powder and transferred to a 100 mL round-bottomed flask (29/32 joint), where it is placed on a rotary evaporator (40 °C, 12 mmHg pressure) for 1 h. The resulting white solid is ground to a fine white powder using a 10 cm diameterglass mortar and pestle, retransferred to a 100 mL round-bottomedflask and dried on a high vacuum line (25 °C, 0.1 mmHg pressure) for 2 h giving the title compound 1 (20.72 g, 134 mmol, 89% yield) (Note 7) as a fine white powder

Stereoselective titanium-mediated aldol reactions of a chiral lactate-derived ethyl ketone with ketones

Aldol reactions of titanium enolates of lactate-derived ethyl ketone 1 with other ketones proceed in a very efficient and stereocontrolled manner provided that a further equivalent of TiCl4 is added to the reacting mixture. The scope of these reactions encompasses simple ketones such as acetone or cyclohexanone as well as other ketones that contain potential chelating groups such as pyruvate esters or α- and β-hydroxy ketones

Substrate-controlled Michael additions of titanium enolates from chiral α-benzyloxy ketones to conjugated nitroalkenes

Lewis acid-mediated substrate-controlled reactions of the titanium(IV) enolates of chiral a-benzyloxy ketones with conjugated nitroalkenes give the 2,4-anti-4,5-syn Michael adducts in good yields and diastereomeric ratios. The supplementary Lewis acid plays a key role in the outcome of these transformations, probably as a consequence of the formation of bimetallic enolates that increase the reactivity of the enolate and direct the approach of the nitroalkene. Importantly, the most appropriate Lewis acid depends on the electrophilic partner: TiCl4 is the most suitable Lewis acid for b-aryl nitroalkenes while the best results for b-alkyl nitroalkenes are obtained with SnCl4. Finally, the nitro group of the resultant compounds can be converted into the corresponding amino, oxime, and nitrile groups under mild conditions, which permits the synthesis of a variety of enantiomerically pure derivatives with excellent yields

Stereoselective alkylation of (S)-N-acyl-4-isopropyl-1,3-thiazolidine-2-thiones catalyzed by (Me3P)2NiCl2

The structurally simple (Me3P)2NiCl2 complex catalyzes SN1-type alkylations of chiral N-acyl thiazolidinethiones with diarylmethyl methyl ethers and other stable carbenium cations. The former can contain a variety of functional groups and heteroatoms at the α-position. The resultant adducts are isolated as single diastereomers in high yields and can be converted into enantiomerically pure derivatives in a straightforward manner