Regioselective Synthesis and Diels−Alder Reaction of 3,4-Dimethylpenta-1,3-diene. Conformational Study of Bicyclic Adducts Structures by ¹H NMR (NOESY, ASIS) and Molecular Modeling (MM2, AM1, RHF, and DFT)

Abstract

A three-step, regioselective synthesis of 3,4-dimethylpenta-1,3-diene 1 has been developed. The condensation of acetone diethylacetal with ethyl propenyl ether yielded, after hydrolysis of the resulting triethoxy adduct 10, 2,3-dimethyl-2-butenal 7. Wittig reaction of 7 with methylenetriphenylphosphorane afforded desired diene 1 in 31% overall yield, easily scalable to the 10 g level. Diels−Alder reaction of 1 with maleic anhydride in benzene was known to afford a 50:50 mixture of “normal” (2) and “rearranged” (3) adducts. In THF as solvent, 2 has been reproducibly obtained in over 90% yield as a 98:2 mixture with 3. 1H NMR spectroscopy (NOESY, ASIS) and molecular modeling (MM2, AM1, ab initio) have been used jointly to determine the conformation of 2 and 3. All are consistent with a folded structure of “rearranged” 3. On the other hand, only RHF/6-31G* and B3LYP/6-31G* ab initio models were in agreement with NMR spectroscopy for an extended conformation of adduct 2. In this case, neither MM2 nor AM1 models gave results consistent with NMR: discrepancies as high as 30° were noted for some dihedrals between these models and ab initio ones.

Regioselectivity Switch Towards the Development of Innovative Diels‐Alder Cycloaddition and Productive Applications in Organic Synthesis

“…In terms of selectivity, DA cycloaddition is a well‐known phenomenon that contributes to the expansion of a wide range of compounds with intricate capabilities and controlled stereochemistry [37–39] . Numerous synthetic accomplishments have been established so far with exceptional efficacy based on various selectivity characteristics in order to create top‐notch organic frameworks [40–45] . This review aims to compile the work based on selectivity in cycloaddition protocols to generate a systematic, synthetically valuable composition in organic synthesis, inspired by the distinct results accumulated by the DA reaction.…”

“…[37][38][39] Numerous synthetic accomplishments have been established so far with exceptional efficacy based on various selectivity characteristics in order to create top-notch organic frameworks. [40][41][42][43][44][45] This review aims to compile the work based on selectivity in cycloaddition protocols to generate a systematic, synthetically valuable composition in organic synthesis, inspired by the distinct results accumulated by the DA reaction. Furthermore, the review explains how to access a wide range of compounds by comprehending the stereocontrol aid supplied by intrinsic and extrinsic characteristics.…”

Stereoselective Synthesis of Highly Substituted γ‐Lactams by the [3 + 2] Annulation of α‐Siloxy Allylic Silanes with Chlorosulfonyl Isocyanate.

“…The combined organic layers were washed with saturated aqueous NaCl (150 mL). The resultant organic phase was dried over MgSO 4…”

“…The raw frame data was processed using SAINT 2 and SADABS 3 to yield the reflection data file. Subsequent calculations were carried out using the SHELXTL 4 program. There were no systematic absences nor any diffraction symmetry other than the Friedel condition.…”

Synthesis of 1,9‐Dideoxy‐pre‐axinellamine

“…A Diels-Alder reaction between dimethyl fumarate and diene 7 [7] (> 95 %, directly carried to the next step) set three of the key stereochemical relationships (verified by X-ray crystallographic analysis of 8) that would eventually manifest themselves in the cyclopentane core. Functional group interchanges involving conversion of the ester groups to azides and deprotection of the silyl group (64 % over five steps) afforded allyl alcohol 9.…”