Diastereoselective Synthesis of Homoallylic Alcohols with Adjacent Tertiary and Quaternary Centers by Using Functionalized Allylic Aluminum Reagents

Abstract

Al be there for you: Sensitive functional groups, including ester and cyano groups, can be present in allylic aluminum reagents prepared by aluminum insertion in the presence of InCl3. These aluminum organometallic compounds undergo addition reactions to various functionalized aldehydes or ketones with remarkable diastereoselectivities allowing the construction of two adjacent quaternary and tertiary centers (see scheme).

Bismuth‐Mediated Diastereoselective Allylation Reaction of Carbonyl Compounds with Cyclic Allylic Halides or Cinnamyl Halide

“…In comparison, except indium metal which mediated the reaction in 79% NMR yield with relatively good diastereoselectivity (entry 2), the use of other metals mostly led to poor product yields (entries 3–10). Although Knochel and co‐workers have reported that pre‐prepared cyclic allylic aluminium or zinc reagents could efficiently react with carbonyl compounds to afford the corresponding homoallylic alcohols with excellent diastereoselectivity, Al and Zn powder almost failed to promote the allylation reaction under optimized reaction conditions. Encouraged by the above results, subsequently we continued our task to explore the substrate scope of the reactions by using various aldehydes and cyclic allylic halides as substrates.…”

“…For instance, when biphenyl 1 q containing both formyl and acetyl substituents were treated with cyclic allylic bromide 2 a in the presence of bismuth and LiI under the well‐established reaction conditions, the reaction took place regioselectively at the formyl group, leading to the expected product 3 u in 96% yield with >99:1 dr (Scheme ). The reluctancy of acetyl group to participate in the allylation reaction clearly indicated that the in situ formed allylic bismuth reagent was a mild organometallic reagent, when compared to its allylic aluminium or zinc counterparts which might react with both aldehyde and ketone without regioselectivity.…”

“…When γ‐substituted allylic halides were used as substrates, normally the reactions proceeded via an S N 2’‐type pathway to generate a mixture of two diastereomers, having the potential to predominantly produce only one diastereomer, depending on the substrates used. For typical examples, Knochel and co‐workers have demonstrated that pre‐prepared cyclic allylic aluminium or zinc reagents, derived from the insertion of metal into cyclic allylic halides, could efficiently react with carbonyl compounds to afford the corresponding homoallylic alcohols with excellent diastereoselectivity. However, in their cases, the reactions need to be performed under strictly anhydrous conditions with the use of preformed cyclic allylic metallic reagents.…”

Titanium‐Catalyzed Hydroalumination of Conjugated Dienes: Access to Fulvene‐Derived Allylaluminium Reagents and Their Diastereoselective Reactions with Carbonyl Compounds

“…In contrast, achieving such a level of selectivity with ketones is rare 12. Recently, the highly diastereoselective addition of cyclic allylalanes onto methylketones was described 4a. We thus decided to investigate ketones in our catalytic conditions (Table 4).…”

Generation of ϵ,ϵ‐Difluorinated Metal‐Pentadienyl Species through Lanthanide‐Mediated C−F Activation

“…We further studied the influenceo ft he aryl group next to the CF 3 group on the reactivity.B enzofulvenes 1b-d with a p-Cl or p-methyl substituted phenylg roup or at hiophener ing afforded the expectedp roducts 4p-r in good to excellent yields upon reaction with p-bromobenzaldehyde 3a under standardc onditions (entries [17][18][19]. In contrast, no CÀFa ctivation reaction was observed in the case of the strongly electron-donatingN Me 2 group at the para position of benzofulvene 1e (entry 20).…”