Stereoselective Synthesis and Retentive Trapping of α‐Chiral Secondary Alkyllithiums Leading to Stereodefined α,β‐Dimethyl Carboxylic Esters

Abstract

The treatment of α-chiral secondary alkyl iodides with tBuLi at -100 °C leads to the corresponding secondary alkyllithiums with high retention of configuration. Subsequent quenching with various electrophiles such as Bu2 S2 , DMF, MeOB(OR)2 , or Et2 CO provides the desired products with retention of configuration. Furthermore, a transmetalation with CuBr⋅P(OEt)3 also allows retentive trapping with acid chlorides and ethylene oxide. The quenching of the resulting alkyllithiums with ClCO2 Et furnishes stereoselectively syn- and anti-ethyl-2,3-dimethyl ester carboxylates (d.r.>94 %). Related esters bearing three adjacent stereo-controlled centers (stereotriads) have also been prepared. This method has been applied to the synthesis of the ant pheromone (±)-lasiol in 26 % overall yield (four steps) with d.r.=97:3 starting from commercially available cis-2,3-epoxybutane.

Diastereo‐ and Enantioselective Cross‐Couplings of Secondary Alkylcopper Reagents with 3‐Halogeno‐Unsaturated Carbonyl Derivatives

“…The cross‐coupling of syn ‐4 a with either E ‐ 5 l or E ‐ 5 m provided the unsaturated ester syn ‐ 3 f in 45–52 % yield with moderate diastereoselectivity (dr>80:20, entry 5). To our delight, we could expand this cross‐coupling to other secondary alkylcopper reagents ( syn ‐ and anti ‐4 b ‐ c ) with the iodenoate ( Z ‐ 5 i ) (entries 6–9). Thus, the reaction of the secondary alkylcopper reagent syn ‐4 b with ( Z )‐ 5 i afforded the corresponding α,β‐unsaturated ester syn ‐ 3 g in 73 % yield and dr=95:5 (entry 6).…”

Regio‐ and Stereoselective Allylic Substitutions of Chiral Secondary Alkylcopper Reagents: Total Synthesis of (+)‐Lasiol, (+)‐13‐Norfaranal, and (+)‐Faranal

“…Herein, we report that chiral secondary alkylcopper reagents of type 3 may undergo regioselective S N 2 or S N 2′ substitutions with various allylic electrophiles ( 4 A or 4 B ), leading to the corresponding S N 2 products 5 or the S N 2′ products 6 with high regio‐ and stereoselectivity. The method efficiency was demonstrated in the enantioselective synthesis of three pheromones, namely (+)‐lasiol ( 7 ), (+)‐13‐norfaranal ( 8 ), and (+)‐faranal ( 9 ; Scheme b) …”

“…Also, the anti ‐1,2‐dimethyl‐substituted alkylcopper reagent anti ‐ 3 b reacted with 4 b with retention of configuration to the alkene anti ‐ 5 b (S N 2/S N 2′>99:1, dr=98:2; entry 5). Finally, alkylcopper reagent 2 S ,3 S ‐ 3 c underwent a highly selective S N 2 substitution with 4 b leading to the chiral protected alcohol 2 R ,3 R ‐ 5 c in 71 % yield (S N 2/S N 2′>99:1, dr=98:2, 99 % ee ; entry 6). After TBS removal with TBAF (tetrabutylammonium fluoride), the pheromone (+)‐lasiol ( 7 ) was obtained in 87 % yield (entry 6; dr=98:2, 99 % ee ; 6 steps, 21 % overall yield starting from R ‐ 10 (see Scheme )).…”

Regio‐ und stereoselektive allylische Substitutionen chiraler sekundärer Alkylkupferverbindungen: Totalsynthese von (+)‐Lasiol, (+)‐13‐Norfaranal und (+)‐Faranal

“…Hier berichten wir, dass chirale sekundäre Alkylkupferverbindungen des Typs 3 regioselektiv entweder S N 2‐ oder S N 2′‐Substitutionsreaktionen mit verschiedenen allylischen Elektrophilen ( 4A oder 4B ) eingehen, wodurch die entsprechenden S N 2‐Produkte 5 oder die S N 2′‐Produkte 6 mit hoher Regio‐ und Stereoselektivität gebildet wurden. Die Effizienz der Methode wurde in der enantioselektiven Synthese der drei Pheromone (+)‐Lasiol ( 7 ), (+)‐13‐Norfaranal ( 8 ) und (+)‐Faranal ( 9 ) vorgeführt (Schema b).…”

“…5, Tabelle ). Das Alkylkupferreagens (2 S ,3 S ‐ 3 c ) ging eine hochselektive S N 2‐Substitution mit 4 b ein, die zum chiralen, geschützten Alkohol 2 R ,3 R ‐ 5 c in 71 % Ausbeute (S N 2/S N 2′ >99:1, dr=98:2, 99 % ee ; Nr. 6, Tabelle ) führte.…”