SnCl2/KI-Mediated Allylation Reactions of Formaldehyde in Water

Abstract

An efficient procedure for SnCl 2 /KI-mediated allylation reactions of formaldehyde with a variety of allylic bromides in aqueous solution is reported. Under conditions developed in this effort, various homoallylic alcohols and 2-halohomoallylic alcohols are produced in good to excellent yields.Formaldehyde is an excellent electrophile for one-carbon elongation of organic substances. However, the intrinsic propensity of formaldehyde monomer to undergo polymerization dramatically limits its synthetic utility. As a result, novel procedures have been developed to suppress polymerization either by using a stable formaldehydeorganoaluminum complex or by generating this substance in situ through the conversion of methanol to formaldehyde or hydrolysis of the Eschenmoser's salt. 1 However, carbon-carbon bond-forming reactions with formaldehyde remain a great challenge.Halohomoallylic alcohols 1a,b, which are comprised of C5 units with isoprene-type skeletons, have been employed as useful building blocks in organic syntheses. 2 In addition, these substances could find additional applications in organic synthesis owing to their possible participation in transition-metal-catalyzed cross-coupling reactions that serve as powerful methods for C-C bond formation. 3 However, the preparation of halohomoallylic alcohols 1a and 1b typically employs multistep routes starting with methyl 3-hydroxy-2-methylpropanoate or other equally complicated pathways (Scheme 1, equations 1 and 2).We envisioned that a straightforward procedure for the synthesis of halohomoallylic alcohols 1 would involve the addition of an appropriate allylic organometallic reagent to formaldehyde (Scheme 2). Although metal-mediated 2-haloallylation of aldehydes can be promoted by using B/ Sn, 4 Sn/HBr, 5 and Fe/Cr, 6 2-haloallylation of formaldehyde has not been reported to date. The conditions employed for B/Sn-and Fe/Cr-mediated 2-haloallylation of aldehydes involve the use of nonaqueous solvents and an inert atmosphere. Thus, the intrinsic polymerization reactivity of monomeric formaldehyde prevents it from being used in Lewis acid catalyzed allylation reactions in organic media. Furthermore, typical thermal cracking of paraformaldehyde to generate formaldehyde monomer is a tedious procedure. Since one could employ commercial aqueous solutions of formaldehyde, metal-mediated Barbier-type allylation reactions of formaldehyde would serve as a facile method to prepare functionalized homoallylic alcohols 1. Scheme 1 Multistep synthesis of 2-halohomoallylic alcohols Scheme 2 Straightforward synthesis of 2-halohomoallylic alcoholsTo the best of our knowledge, only scattered reports describe the metal-mediated allylation reactions of formaldehyde in aqueous media using Sn or Zn, 7 Sn/Al, 8 Sn/ InCl 3 , 9 and In. 10 However, in these processes only simple allylic halides were used. Our investigations aimed at the development of metal-mediated allylation and 2-haloallylation reactions of formaldehyde using water as the solvent. 11 Tin and tin-containing Lewis acids ...

Stereoselective Isoxazolidine Synthesis Via Copper-Catalyzed Alkene Aminooxygenation

“…2-Phenyl-but-3-en-1-ol 14 was converted to 1k (120 mg, 56% yield, clear oil). 1 H NMR (400 MHz, CDCl 3 ) δ 7.60 (d, J = 8.0 Hz, 2H), 7.37-7.19 (m, 7H), 6.93 (s, 1 H), 6.02-5.90 (m, 1 H), 5.16-5.07 (m, 2H), 4.31 (d, J = 10.0 Hz, 2H), 3.76-3.68 (m, 1H), 2.42 (s, 3H); 13 C NMR (75.5 MHz, CDCl 3 ) δ 144.7, 140.3, 137.8, 133.3, 129.5, 128.5, 128.4, 128.0, 126.8, 116.5, 79.7, 48.2, 21.6; IR (thin film) 3223, 2960, 1453, 1336, 1167, 1091, 918, 757 cm −1 ; HRMS (ESI) calcd for [M+Na] + C 17 H 19 O 3 N 1 Na 1 S 1 : 340.0969, found: 340.0978.…”

Asymmetric Synthesis of Cyclopentene Compounds Containing All-Carbon Quaternary Stereocenters by (3 + 2) Cycloaddition and Its Application in the Formal Synthesis of (R)-(−)-Puraquinonic Acid

“…Ethyl ester 20 was chemoselectively converted to Weinreb amide 21 . The reaction of 21 with the alkenyllithium derived from alkenyl iodide 22 furnished ketone 23 in moderate yield . Ring-closing metathesis of 23 with the second-generation Grubbs catalyst and 2,6-dichloro-1,4-benzoquinone formed the fused bicyclic skeleton, giving enone 24 in good yield .…”

Methods for the Preparation of Allenes Employing Indium- and Zinc-Mediated Dehalogenation Reactions in Aqueous Solutions

“…The general method most often utilized for the synthesis of allenylmethyl aryl ethers begins with an allenylmethyl bromide, prepared from 2-butyne-1,4-diol, as shown in Scheme . , However, several drawbacks are associated with this method, including difficult separation of the monochloro propargylic alcohol intermediate from the dichloroalkyne byproduct and the need to handle large quantities of lithium aluminum hydride. In recent studies, we observed that allenes are produced as side products in metal-mediated 2-haloallylation reactions of formaldehyde. This finding stimulated an investigation aimed at the development of metal-mediated dehalogenation reactions of vicinal dihalides ( 1 , Scheme ) as a method to generate allenes.…”