Syntheses of Highly Functionalized Spirocyclohexenes by Formal [4+2] Annulation of Arylidene Azlactones with Allenoates

Abstract

A straightforward phosphine-catalyzed formal [4+2] annulation between α-branched allenoates and arylidene azlactones has been developed to access highly functionalized spirocyclohexenes. This cyclization favors the γ-addition of the phosphine-activated allenoates over a β’-addition pathway. Detailed computational studies support the proposed mechanism and provide a reasonable explanation for the observed regioselectivity and the noted effect of the catalyst.

Chiral Isochalcogenourea‐Catalysed Enantioselective (4+2) Cycloadditions of Allenoates

“…[7] A considerable challenge, however, is the fact that chiral catalyst derivatives occasionally show lower reactivities than achiral ones, making identification of a suited chiral catalyst potentially difficult. [8] In addition, sometimes higher catalyst loadings (> 10 mol %) are necessary, which is to some extent due to the possible sensitivity of P(III)-based catalysts towards oxidation.…”

Enantioselective Catalytic [4+1]‐Cyclization of ortho‐Hydroxy‐para‐Quinone Methides with Allenoates

“…By testing other bases, K 2 CO 3 turned out to be the most promising (entry 7). It should be noted that other simple trialkylphosphines were tested as well, but in analogy to our previous observation these did not allow for this [4+1]‐annulation.…”

Recent Advances in Azlactone Transformations

“…Also concerning the multi-activation mode of chiral phosphoric acids, Xiao and co-workers recently reported a highly stereoselective [4+2] cycloadditions between in situ generated ortho-quinone methides (prepared employing ortho-hydroxy benzhydryl alcohols -38) and azlactone enol intermediate (39), providing access to densely functionalized 3,4-dihydrocoumarins (40) (Scheme 12A). [33] Different substrates bearing diverse electronic and steric substituents in both azlactone and orthohydroxy benzhydryl alcohol moieties were well tolerated in the optimized reaction conditions and afforded the desired products with up to 98 % yield, > 95:5 d.r.…”

“…[39] Most interestingly, the γ-addition product (63) was favored over the ′-addition (64). [39] Most interestingly, the γ-addition product (63) was favored over the ′-addition (64).…”

“…Recently, Waser and co‐workers described a method to access densely functionalized spirocyclohexenes through a [4+2] cycloadditions between arylidene azlactones and α‐branched allenoates ( 62 ), catalyzed by a phosphine (Scheme A) . Most interestingly, the γ‐addition product ( 63 ) was favored over the β′‐addition ( 64 ).…”