Improved Synthesis of Cyclic Tertiary Allylic Alcohols by Asymmetric 1,2‐Addition of AlMe₃ to Enones

Abstract

The development of an improved protocol for the enantioselective Rh(I) /binap-catalysed 1,2-addition of AlMe3 to cyclic enones is reported. (31)P NMR analysis of the reaction revealed that the catalyst in its resting state is a chloride-bridged dimer. This insight led to the use of AgBF4 as an additive for in situ activation of the dimeric precatalyst. Thus, the catalyst loading can now be reduced to only 1 mol% with respect to rhodium. Various 5-7-membered cyclic enones can be transformed into tertiary allylic alcohols with excellent levels of enantioselectivity and high yields. The obtained products are versatile synthetic building blocks, shown by a highly enantioselective formal total synthesis of the pheromone (-)-frontalin as well as formation of a bicyclic lactone that has the core structure of the natural flavour component "wine lactone".

Regio- and Stereoselective Addition of HO/OOH to Allylic Alcohols

“…Selective protection of the OOH with TBSCl followed by oxidative cleavage of the vicinal diol and NaBH 4 reduction of the dialdehyde afforded 5 (without any loss of enantiopurity all the way from 2l ). Conversion of 5 into the known triol 6 finally verified the absolute configuration at the C-1 of 2l .…”

“…10 min (TLC showed completion of the reaction), concentrated on a rotary evaporator, and purified by column chromatography (1:15 MeOH/CH 2 Cl 2 ) on silica gel to give the known (( S )-2-methylhexane-1,2,6-triol ( 6 ) as a colorless oil (13 mg, 0.088 mmol, 97% from 5 ). Data for 6 : [α] D 25 −3.1 ( c 1.0, EtOAc) (lit . [α] D 20 −2.1 ( c 1.0, EtOAc)).…”

“…4, 136.3, 132.7, 116.2, 71.6, 44.4, 36.6, 32.4, 27.4, 26.0. FT-IR (film) 3349, 2924, 2853, 1445, 1260, 1030, 801 cm −1 ; EI-MS m/z (%) 152 (M + , 4), 134 (5), 111 (100), 93 (40), 79 (20), 67 (35), 55 (56), 43 (20), 41 ( 37 (±)-5-Methyl-3,6-dihydro-2H-pyran-3-ol (1t). Alcohol 1t was obtained using the same procedure above for "Synthesis of (racemic) 1s", except the starting 7-membered cyclic ketone was replace with the known 26 5-methyl-2H-pyran-3(6H) -one.…”

Recent Advances in Catalytic Asymmetric Synthesis of Tertiary Alcohols via Nucleophilic Addition to Ketones

“…Apart from dialkylzinc, trialkylaluminum was another frequently used reagent in ketone alkylation reactions. In 2013, Zezschwitz and Kolb showed that commercially available AlMe 3 could undergo asymmetric 1,2‐addition reaction to cyclic enones with Rh(I)/( R )‐BINAP 17 as the catalyst (Scheme ) . In this reaction, AgBF 4 was able to activate chloride‐bridged dimeric rhodium catalyst in situ , and thus significantly reduced the catalyst loading to 1 mol% when 1.5 mol% of AgBF 4 was added as the additive.…”

Chiral Brønsted Acid-Catalyzed Asymmetric Allyl(propargyl)boration Reaction of ortho-Alkynyl Benzaldehydes: Synthetic Applications and Factors Governing the Enantioselectivity

“…In view of the need for new efficient strategies for the synthesis of cyclic chiral alcohols, the use of other ortho -functionalized benzaldehydes is described herein, thus expanding the molecular complexity accessible from 2-bromobenzaldehyde, a simple and readily available starting material. Herein, we report the first highly enantioselective allylation of 2-alkynylbenzaldehydes.…”