Controllable Stereoselective Synthesis of (Z)- and (E)-Homoallylic Alcohols Using a Palladium-Catalyzed Three-Component Reaction

Abstract

Diastereoselective synthesis of (Z)- and (E)-homoallylic alcohols using a Pd-catalyzed three-component reaction of 3-(pinacolatoboryl)allyl benzoates, aldehydes, and aryl stannanes was developed, which provides an alternative method for the allylboration of aldehydes using α,γ-diaryl-substituted allylboronates. Both sets of reaction conditions enable access to either (Z)- or (E)-homoallylic alcohols with good to high alkene stereocontrol. The present method showed good functional group compatibility and generality. Efficient chirality transfer reactions to afford enantioenriched (Z)- and (E)-homoallylic alcohols were also achieved.

Copper(I)-Mediated 11C-Carboxylation of (Hetero)arylstannanes

“…Tributyl(p-tolyl)stannane (2a), tributyl(4-methoxyphenyl)stannane (3a), and tributyl(4-trifluoromethylphenyl)stannane (4a) were synthesized according to adapted literature procedures 41,42 and exhibited 1 H, 13 C{ 1 H}, 19 F{ 1 H} NMR (for 4a), and ESI-MS data that agree with those previously reported for the compounds. 43,44 2,5-Dichloro-2,5-dimethylhexane (S1), 45,46 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene (S2), 47,48 4-iodophenyl-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-methanone (S3), 47 and 6-(1-(4-iodophenyl)vinyl)-1,1,4,4,7-pentamethyl-1,2,3,4-tetrahydronaphthalene (S4) 16,49 were prepared according to previously published procedures and exhibited NMR spectral data that agree with those previously published for the compounds.…”

Palladium‐Catalyzed Diastereoselective Synthesis of (Z)‐Conjugated Enynyl Homoallylic Alcohols

“…To gain further insights into the mechanism, we conducted a chirality transfer experiment using (R)-2 a under the optimized reaction conditions (Table 3). Compared to the results from our previous work [5] and those from a related study on Tsuji-Trost allylic alkylation, [24] lower chirality transfer was observed and 4 aaa was obtained in 63% yield with 66% es (entry 1).…”

“…Recently, we demonstrated the advantages of borylated π‐allylpalladium species I in multiple C−C‐bond‐forming reactions (Scheme 1a). For instance, species I can afford ( Z )‐homoallylic alcohols with high diastereoselectivity via the allylation of aldehydes, followed by coupling of the resulting cis ‐vinylpalladium species with organometallic reagents such as triorganoboranes, [5a] arylstannanes, [5b] and vinylstannanes [5c] (Scheme 1a, top). These encouraging results led us to extend this method to the synthesis of ( Z )‐conjugated enynyl homoallylic alcohols toward the exploration of efficient synthetic strategies.…”

“…[28] Scheme 4 shows a plausible reaction mechanism that is based on the above results; this mechanism is similar to that of our previously reported palladium-catalyzed three-component reaction. [5] η 3 -Allylpalladium intermediate A is formed through the oxidative addition of allylic benzoate (R)-2 a to a Pd 0 species. DFT calculations suggested that the stable conformation of A was the cis conformation (see Figure 1).…”

Versatile Reactivity of Metalloid‐Substituted π‐Allylpalladium Species

“…In addition to the successful palladium‐catalyzed three‐component reaction of B(pin)‐substituted allyl acetates, aldehydes, and triorganoboranes, the use of arylstannanes instead of triorganoboranes provided both ( Z )‐ and ( E )‐homoallylic alcohols possessing aryl groups at the alkene terminus using a catalyst‐controlled strategy (Scheme 20). [42] A Pd(OAc) 2 /P(4‐MeOC 6 H 4 ) 3 catalyst system with acetonitrile as a solvent afforded ( Z )‐ anti ‐homoallylic alcohols with good to high stereocontrol of the alkene. Conversely, stereochemical changes to afford the ( E )‐ anti ‐isomer were observed when Pd 2 (dba) 3 was employed in the absence of ligands together with the addition of 5 Å molecular sieves (MS 5 Å).…”