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

Direct and Asymmetric Aldol Reactions of N-Azidoacetyl-1,3-thiazolidine-2-thione Catalyzed by Chiral Nickel(II) Complexes. A New Approach to the Synthesis of -Hydroxy--Amino Acids

A direct and asymmetric triisopropylsilyltrifluoromethanesulfonate (TIPSOTf) mediated aldol reaction of N-azidoacetyl-1,3-thiazolidine-2-thione with aromatic aldehydes catalyzed by a chiral nickel(II)-Tol-BINAP complex has been developed (BINAP=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl). The catalytic protocol gives the corresponding anti α-azido-β-silyloxy adducts with outstanding stereocontrol and in high yields. Theoretical calculations account for the stereochemical outcome of the reaction and lay the foundations for a mechanistic model. In turn, the easy removal of the thiazolidinethione yields a wide array of enantiomerically pure derivatives in a straightforward and efficient manner. Such a noteworthy character of the heterocyclic scaffold together with the appropriate manipulation of the azido group open a new route to the synthesis of di- and tripeptide blocks containing a β-aryl-β-hydroxy-α-amino acid

Direct and enantioselective aldol reactions catalyzed by chiral nickel(II) complexes

A direct and asymmetric aldol reaction of N-acylthiazinanethiones with aromatic aldehydes catalyzed by chiralnickel(II) complexes is reported. The reaction gives thecorresponding O-TIPS-protected anti-aldol adducts in highyields and with remarkable stereocontrol and atom economy.Furthermore, the straightforward removal of the achiralscaffold provides enantiomerically pure intermediates ofsynthetic interest, which involve precursors for anti-a-amino-b-hydroxy anda,b-dihydroxy carboxylic derivatives. Theoret-ical calculations explain the observed high stereocontrol