Facile synthesis of 3-aryl 2,3-dihydrobenzofurans via novel domino 1,6-addition/O-alkylation reactions of para-quinone methides

Recent Advances in Synthetic Strategies to 2,3-Dihydrobenzofurans

“…47 Zhou and co-workers (2018) described the use of bromomalonate as the nucleophile precursor together with o-hydroxyphenyl-substituted p-quinone methides thus obtaining diethyl 3-aryl-DHB-2,2-dicarboxylates in up to 99% yield (Scheme 10, route B). 48 In 2019, Waser and co-workers started from o-hydroxyphenyl-substituted p-quinone methides in an asymmetric catalytic synthesis of highly functionalized DHBs. 49 The reaction relied on a formal [4+1]-annulation of these quinone methides with allenoates in the presence of a commercially available chiral phosphine catalyst.…”

Enantioselective Catalytic [4+1]‐Cyclization of ortho‐Hydroxy‐para‐Quinone Methides with Allenoates

“…The 2,3-dihydrobenzofuran scaffold is ap rominent structural motif foundi nn umerous biologically active (natural) compounds [1] and the development of novel synthesis strategies to access these targets has been ah eavily investigatedt opic over the last years. [2][3][4][5][6][7][8] One especially appealing approach to access chiral 2,3-dihydrobenzofurans is the formal [4+ +1]-cyclization [9] between as uitable C1 buildingb lock and ac arefully chosen (maybe in situ generated)a cceptor-donor containing C4 building block. The mostv ersatile class of C4 building blocks used to obtain the dihydrobenzofuran skeleton 1 via af ormal [4+ +1]cyclization are ortho-quinone methides (o-QMs) 2.…”

“…[6] Alternatively,t he hydroxy-containing para-quinone methides 3 have very recently emergeda sp owerful building blocks for formal (4 + n)-annulations as well. [7,[11][12][13] Interestingly however,t heir applicability for asymmetric[ 4 + +1]-cyclizations to access dihydrobenzofurans 1 has so far been ratherl imited,w ith highly asymmetric protocols still being rare (Scheme 1B). [7] Twoy ears ago we reported the first highly enantioselective synthesis of compounds 1 by reactingp reformed chiral ammonium ylides with in situ formed o-QMs 2.…”

“…[7,[11][12][13] Interestingly however,t heir applicability for asymmetric[ 4 + +1]-cyclizations to access dihydrobenzofurans 1 has so far been ratherl imited,w ith highly asymmetric protocols still being rare (Scheme 1B). [7] Twoy ears ago we reported the first highly enantioselective synthesis of compounds 1 by reactingp reformed chiral ammonium ylides with in situ formed o-QMs 2. [4c] More recently we found that the highly functionalized allenoates 4 can undergo av ery unique (and up to then unprecedented)f ormal [4+ +1]-cyclization with accept-ors 2 in the presenceo fastoichiometric amount of PPh 3 (Scheme 1C).…”

DataSheet1.PDF

“…Inspired by the seminal works of Fan and Jorgensen (Chu et al, 2013;Caruana et al, 2014), numerous of methods utilizing p-QMs as vinylogous Michael acceptors have been successfully developed through 1,6-conjugate addition and annulation reactions (Lou et al, 2015;Wang et al, 2015;Deng et al, 2016;Dong et al, 2016;He et al, 2016;Li et al, 2016;Ma et al, 2016;Zhang et al, 2016;Roiser and Waser, 2017;Zhang et al, 2017). Recently, Enders and co-workers first demonstrated the potential of ortho-hydroxyphenyl-substituted p-QMs in [4 + 2] cyclization reaction (Zhao et al, 2016), which subsequently enables the extensively investigation of [4 + 1] ( Chen et al, 2018;Liu L. et al, 2018;Xiong et al, 2018;Zhi et al, 2018;Zhou et al, 2018;Lu et al, 2019;Tan et al, 2019) [4 + 2] (Jiang X. L. et al, 2018;Mei et al, 2018;Zhang et al, 2018;Yang et al, 2019;Zhang et al, 2019;Huang et al, 2020;Roy et al, 2020;Tan et al, 2020;You et al, 2020) and [4 + 3] (Jiang F. et al, 2018;Li et al, 2018 Q Chen et al, 2019) annulations by various research groups. Although great progress has been witnessed in this field, the employment of p-QMs substrates in the construction of heterocyclic frameworks, especially nitrogen-containing heterocyclic frameworks, still remains underdeveloped (Scheme 1A).…”