A highly diastereoselective synthesis of deep molecular baskets

Abstract

We describe a preparative method for directing Mizoroki-Heck cyclotrimerization of enantioenriched bromonorbornenes into molecular baskets having increasingly deeper and extendable aromatic cavities. Such diastereoselective cyclotrimerizations of the bromo-olefinic substrates resulted...

Enantioselective Construction of Modular and Asymmetric Baskets

“…Recently,w er eported an enantioselective method for preparing multigram quantities of (À)-2 (Scheme 1A) [33] from inexpensive (À)-dimenthyl fumarate and cyclopentadiene. That is to say, l-(À)-menthol ($140 kg À1 ,Sigma-Aldrich) was used as chiral auxiliary for stereoselective synthesis of cycloadduct (À)-1 M ,f ollowed by its conversion into (À)-2 (98 % ee).…”

“…Using (À)-1 iB ,weprepared (+ +)-2 by following the same optimized route for converting (À)-1 M into (À)-2. [33,34] With both enantiomers of 2 in hand, we went on to probe the sequential ABC couplings in the preparation of previously studied basket 8 (Scheme 2, strategy 1). [33] Chemoselective borylation of (À)-2 into fragment A ((À)-3, Scheme 2) was conducted with CuI and bis(pinacolato)diboron.…”

“…[33,34] With both enantiomers of 2 in hand, we went on to probe the sequential ABC couplings in the preparation of previously studied basket 8 (Scheme 2, strategy 1). [33] Chemoselective borylation of (À)-2 into fragment A ((À)-3, Scheme 2) was conducted with CuI and bis(pinacolato)diboron. [40] To obtain fragment B (Scheme 2), (À)-2 was deprotonated with LDAa nd then the electrophilic 1,2-diiodoethane was added to give iodobromonorbornene (+ +)-4.Finally,(+ +)-2 was borylated under the same conditions as its enantiomer to produce fragment C ((+ +)-3,Scheme 2).…”

“…[43a] In contrast to directed and stepwise preparation of (+ +)-11 (Figure 2A), we decided to probe its one-pot synthesis by using the Mizoroki-Heck procedure optimized for head-totail coupling of enantioenriched bromonorbornenes (Scheme 3). [33] By starting with A, B,a nd C,h olding tBu, Me,a nd Et ester groups,r espectively (Scheme 3), we obtained ac omplex mixture of basket products,i ncluding racemic 11 (Figure S49). As the coupling may start with either A, B,orC,the multitude of the observed products (Scheme 3) is unsurprising.D espite ag reat appeal of the one-pot procedure,t he process is evidently fraught with difficulties related to the reactionsc hemo-and stereoselectivity as well as the need to isolate the desired product from ac omplex mixture.…”

Enantioselective Construction of Modular and Asymmetric Baskets

“…[43a] In contrast to directed and stepwise preparation of (+ +)-11 (Figure 2A), we decided to probe its one-pot synthesis by Angewandte Chemie using the Mizoroki-Heck procedure optimized for head-totail coupling of enantioenriched bromonorbornenes (Scheme 3). [33] By starting with A, B,a nd C,h olding tBu, Me,a nd Et ester groups,r espectively (Scheme 3), we obtained ac omplex mixture of basket products,i ncluding racemic 11 (Figure S49). As the coupling may start with either A, B,orC,the multitude of the observed products (Scheme 3) is unsurprising.D espite ag reat appeal of the one-pot procedure,t he process is evidently fraught with difficulties related to the reactionsc hemo-and stereoselectivity as well as the need to isolate the desired product from ac omplex mixture.…”