2-(Chloromethyl)-3,5-dioxahex-1-ene. An effective acetonylating reagent

Synthesis of 2-(3-hydroxy-2-methyl-1-alkenyl)-1-pyrrolines and 2-(3-hydroxybutyl)-1-pyrroline using α-lithiated 2-methyl-1-pyrroline

“…The latter electrophile was easily prepared from 1,3-dichloro-2-(methoxymethyloxy)propane through a dehydrochlorination process. 16 Thus, treatment of 2-methyl-1-pyrroline (1) with 1.1 equiv of LDA and 1.2 equiv of 3-chloro-2-(methoxymethyloxy)-1-propene in THF afforded the corresponding alkylated pyrroline 8 in 82% yield after 15 h at room temperature. Subsequent hydrolysis of the acetal moiety in the latter pyrroline 8 by means of 7 equiv of an aqueous solution of hydrochloric acid (0.5 M) yielded the desired g-iminoketone 3a after reflux for 4 h in a dichloromethane/water solvent system (Scheme 4).…”

“…After 5 min, the solution was cooled to À78 C and 2-methyl-1-pyrroline 1 (20 mmol), dissolved in dry THF (20 mL), was added dropwise. The reaction mixture was then stirred for 2 h at À78 C. Finally, a solution of 3-chloro-2-(methoxymethyloxy)-1-propene 16 temperature. Workup was carried out by pouring the reaction mixture in an aqueous sodium hydroxide solution (75 mL, 0.5 M), followed by extraction with diethyl ether (2Â75 mL, 1Â50 mL).…”

Domino Aza‐Claisen/Mannich Cyclization Reaction from a Chiral α‐Alkoxy Enamine or Sequential Alkylation of an α‐Alkoxy Ester Enolate or Nitrile Anion, Followed by an Intramolecular Wittig Reaction: Two (3+2) Annulation Routes to Homochiral 4‐Alkyl‐4‐hydroxy‐2‐cyclopentenone Synthesis

“…Thus, treatment of aldehyde 1 with pyrrolidine, according to the conditions described by Secrist III20 for the C‐4 allylation of nucleoside, afforded the pyrrolidino enamine intermediate 2 as a mixture of Z / E diastereoisomers. The crude 2 obtained after evaporation of the solvent was directly N ‐alkylated at 80 °C in MeCN, with freshly prepared 3‐iodo‐2‐(methoxymethoxy)prop‐1‐ene ( 3 ) 21. Surprisingly enough, the product obtained after conventional workup was not the expected C‐4 allylated aldehyde resulting from the (3,3)‐rearrangement (3‐aza‐Claisen) but the target cyclopentenones 4 and 5 directly as a mixture of diastereoisomers, thus obtained in 40% yield but in one‐pot fashion from aldehydes 1 or 1′ by a domino reaction (Scheme ).…”

Asymmetric Synthesis of (S)‐4‐Oxopipecolic Acid by a 3+3 Atom‐Unit Assembly Strategy

“…Reagent 3 was prepared conveniently in high yield by using the literature procedure. [22] Deprotonation of N-(cyanomethyl)-4-phenyloxazolidine (2) [23] with LDA/HMPA at low temperature, and treatment of the resulting anion with 3, gave a mixture of the two diastereoisomers 4a and 4b in a 71:29 ratio with an overall yield of 79%. All known previous alkylations of 2 by using this procedure [18,23Ϫ25] were known to give preferentially the (S) configuration at the new chiral centre and we assumed, for the time being, that this would also be the case for the major isomer 4a.…”

“…Diisopropylamine and HMPA were distilled under argon from CaH 2 . Compounds 2 [23] and 3 [22] were prepared in high yields and purity according to literature procedures without any significant modifications. All other reagents and solvents were used as obtained from commercial sources without further purification.…”