Boronic ester annulation

Figure 15.16 Boronic ester annulation, including a Diels-Alder reaction, developed by Micalizio and Schreiber [47].

Notably, allylboronates can also be successfully used in a ruthenium-catalyzed cross-metathesis/aUyboration sequence for the synthesis of homoaUylic alcohols [109,110]. Likewise, an unsaturated boronic ester annulation strategy with allylic and propargylic alcohols have found very elegant and useful applications in diversity-oriented organic synthesis (Scheme 9.53) [111]. 

A novel class of quinone boronic esters has been prepared via a Dotz annulation of Fischer carbene complexes with alkynylboronates. The origin of the high regioselec-tivity is discussed in terms of steric and electronic effects. Additionally, these compounds undergo Pd-catalyzed coupling reactions to give substituted quinones and hy-droquinones (Scheme 9.49) [102]. 

Palladium-catalyzed annulation reactions of conjugate acceptors and allenyl boronic ester provide substituted cyclopentenes in high yields and diastereose-lectivities (Scheme 6.24). These reactions are hypothesized to commence by the conjugate addition of a nucleophilic propargyl-palladium complex. Transmetalation of allenylboronic acid pinacol ester with a Pd(II) catalyst proceeds via an SE2 mechanism to provide the propargyl-palladium complex, which on conjugate attack on the electrophile furnishes an allene intermediate. Finally, endo carbopalladation of the pendant allene and protodepalladation generates the cyclopentene [28]. 

Later, this cycloaddition reaction was improved by the pretreatment of the enamide ester with an equimoler amount of trialkylsilyl trifluoromethanesul-fonate and triethylamine at ambient temperature. The synthesis of tyro-phorine (119) was achieved by the above improved method (Scheme 55). The enamide ester 441 was subjected to annulation using t-butyldimethylsilyl triflate and triethylamine at 15°C to produce the bicyclic lactam 442 in 68% yield. Oxidation of 442 with thallium(III) trifluoroacetate and boron triflu-oroetherate in a mixture of dichloromethane and trifluoroacetic acid at 4°C produced (83%) the pentacyclic compound 443. Hydrolysis of 443, followed by decarboxylation of the resultant acid, gave the pentacyclic lactam 444. Reduction of 444 with sodium bis(2-methoxyethoxy)aluminum hydride in refluxing dioxane afforded tyrophorine (119) (85CC1159). 

Historical perspective C. H. Heathcock, Comp. Org. Syn. 2, 133-179 (1991). General review T. Mukaiyama, Org. React. 28,203-331 (1982). Application of lithium and magnesium enolates C. H. Heathcock, Comp. Org. Syn. 2, 181-238 (1991) of boron enolates B. M. Kim etal, ibid. 239-275 of transition metal enolates I. Paterson, ibid. 301-319. Stereoselective reactions of ester and thioester enolates M. Braun, H. Sacha, J. Prakt. Chem. 335,653-668 (1993). Review of asymmetric methodology A. S. Franklin, I. Paterson, Contemp. Org. Syn. 1,317-338 (1994). Cf. Claisen-Schmidt Condensation Henry Reaction Ivanov Reaction Knoevenagel Condensation Reformatskv Reaction Robinson Annulation. 

Cross-coupling/Heck reaction cascade was accomplished with o-bromophenyl-boronic acid (179) and l-bromo-2-(l-alkenyl)arenes 204 and 8-bromo a,, y,h-unsaturated esters 206 and 208 with a palladium catalyst (Scheme 22.47) [70], The flve-membered ring formation proceeded smoothly in the presence of Pd(OAc)2, PPhs, and CS2CO3 upon heating the DMF solution at 60 to 70 °C to give 205, 207, and 209 in good yields. When the reaction of 179 and 208 was carried out at 120 °C, the annulation was followed by isomerization to produce 210 in 65% yield. 

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