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A New Approach to the Synthesis of Long‐Chain Polypropionates Based on the Diels‐Alder Monoadditions of 2,2′‐Ethylidenebis[3,5‐dimethylfuran]
Author(s) -
Ancerewicz Jacek,
Vogel Pierre
Publication year - 1996
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19960790513
Subject(s) - chemistry , diels–alder reaction , alder , chain (unit) , organic chemistry , stereochemistry , catalysis , botany , physics , astronomy , biology
Acidic condensation of 2,4‐dimethylfuran with acetaldehyde provided 2,2′‐ethylidenebis[3,5‐dimethylfuran] ( 7 ) which added 1 equiv. of methyl bromopropynoate to give a major adduct 8 . Regio‐ and stereoselective hydroboration of the latter 7‐oxanorbornadiene derivative followed by alcohol protection and methanolysis of its β‐bromoacrylate moiety gave (1 RS ,2 RS ,4 RS ,5 SR ,6 SR ,1′ RS )‐methyl 4‐[1′‐(3″,5″‐dimethylfuran‐2″‐yl)ethyl]‐3,3‐dimethoxy‐6‐ exo ‐[(2‐methoxy)ethoxy]‐1,5‐ endo ‐dimethyl‐7‐oxabicyclo[2.2.1]heptane‐2‐ endo ‐carboxylate ( 24 ) ( Schemes 2 and 3 ). Reduction of 24 with LiAlH 4 , followed by H 2 O and MeOH elimination gave the 3‐methyl‐idene‐7‐oxanorbornan‐2‐one derivative 26 which underwent 7‐oxa ring opening through a S N 2′ type of reaction with Me 2 CuLi ( Scheme 4 ). Stereoselective hydrogenation and ketone reduction provided (1 RS , 2 SR ,3 RS ,4 RS ,5 RS ,6 RS ,1′ SR )‐1‐ [1″‐(3 ″,5″‐dimethylfuran‐2″‐yl)]‐ c ‐3‐ethyl‐ c ‐5‐[(2‐methoxyethoxy)m e‐ c ‐ethyl‐ c ‐ c ‐5‐(2‐methoxyethoxy)methoxy]‐ t ‐4, t ‐6‐dimethyl‐cyclohexane‐ r ‐1, c ‐2‐diol ( 32 ), the oxidative cleavage of which with Pb(OAc) 4 generated a 6‐oxo‐aldehyde 33 ( Schemes 4 and 5 ). Chemoselective protection of 33 and chemo‐ and stereoselective reductions generated (2 RS ,3 RS ,4 SR ,5 SR ,6 SR ,7 RS )‐7‐(3′,5″‐dimethylfuran‐2′‐yl)‐2‐ethyl‐6‐hydroxy‐4‐[(2‐methoxyethoxy)methoxy]‐3,5‐dimethyloct‐1‐yl pivaloate ( 36 ) and its 4‐hydroxy 6‐epimer 40 (12 and 13 steps, resp., from adduct 8 ; Scheme 5 ). Oxidation of the furan ring of 36 led to a (2 RS ,3 SR ,4 RS ,5 SR ,6 RS ,7 RS )‐7‐ethyl‐3,5,8‐trihydroxy‐2,4,6‐trimethyl‐octanoic acid derivative 44 , a polypropionate fragment with six contiguous stereogenic centres ( Scheme 6 ).