Enantioselective Synthesis of β‐Iodo Morita–Baylis–Hillman Esters by a Catalytic Asymmetric Three‐Component Coupling Reaction

Abstract

A catalytic route toward chiral Morita-Baylis-Hillman esters by asymmetric coupling between alpha,beta-acetylenic esters, aldehydes, and trimethylsilyl iodide has been developed (see scheme). The reaction proceeds with high to excellent enantioselectivities, and the products can be transformed into beta-branched derivatives in a single step and with excellent retention of configuration. TMS = trimethylsilyl.

Application of aluminum triiodide in organic synthesis

“…Several olefins (170 and 173) were prepared by this method (Scheme 14). 104 It is noteworthy that both cis-diol (169) and trans-diol (17) afforded the same olefin (170), indicating that the conversion proceeded in a stepwise manner (Scheme 14). Recently, 5-hydroxymethylfurfural (HMF, 176), a biomass-derived precursor for biofuel, was accessed through deoxydehydration of -glucopyranose (175) with AlI 3 in dimethylacetamide (DMAc).…”

“…Thus transition state 284b was favored over 284a, as illustrated in Scheme 24D. 168,169 Other Lewis acids effective in preparation of β-I-MBH esters include magnesium iodide, TMSI 170 and BF 3 •Et 2 O-TBAI. 171,172 Interestingly, E-β-I-MBH esters could be achieved stereoselectively with BF 3 •Et 2 O-TMSI.…”

Efficient Assembly of 2,5,6-Substituted Pyrimidines via MgI2-Mediated Morita−Baylis−Hillman Reaction

“…We were especially interested in utilizing the MBH reaction because of the wide substrate tolerance, commercial availability, and ease of synthesis of the starting materials 13–15. The Lewis acid activated MBH-type coupling of aldehyde with propiolic esters to produce substituted α-(hydroxymethyl)-iodoacrylates, 7 (Scheme 1) has been well documented in recent years 16–28. Various groups have reported isolation of E or Z-selective synthetic methodologies towards substituted α-(hydroxymethyl)-iodoacrylates.…”

“…Among the various Lewis acids that have been used: TiCl 4 /Me 2 S,20 BF 3 .Et 2 O/TMSI,21 ZrCl 4 /( n -Bu) 4 -NI,22 TiCl 4 /( n -Bu) 4 NI,23 Et 2 AlI17,24 and MgI 2. 25–28 MgI 2 is readily available, non-toxic and less sensitive to moisture. We herein report a new three step method involving the MgI 2 mediated MBH type reaction, Dess-Martin periodinane oxidation of the MBH adduct and subsequent condensation with amidine or guanidine derivatives produces a diverse 2, 6-disubstituted pyrimidines-5-carboxylate library.…”

“…We synthesized a small library of substituted α-(hydroxymethyl)-iodoacrylates via MgI 2 -promoted MBH reaction using a modified procedure of Pare’ et al 25–28. This method predominantly generates Z-olefin as the major product.…”