Biaryl aldehyde

The Leznoff acetal linker 69 was used to anchor an aldehyde to the solid support and following a series of reactions, the aldehyde was released by acidic cleavage [78]. An application of this resin was demonstrated for a biaryl aldehyde library synthesis which incorporated a Suzuki-Miyaura reaction (Scheme 37) [79]. Cleavage was effected by a solution of 3 M HC1... 

Installation of a different side chain completely alters the pharmacological profile leading to a new class of muscle relaxants. The synthesis begins with copper(II)-promoted di-azonium coupling between furfural (IJ ) and 3,4-dichlorobenzene-diazonium chloride (15) to give biaryl aldehyde 1. Next, condensation with 1-aminohydantoin produces the muscle relaxant clodanolene (17). ... 

This transfer of chirality can occur in the absence of the chiral oxazoline group. Thus 5, obtained by cleavage of the oxazoline group ol 3, was oxidized by DDQ to the biaryl aldehyde (S)-(-)-6 (90% ee). 

Van der Eycken and co-workers [179] have reported a microwave-assisted A -MCR of an aniline, an alkyne and biaryl aldehyde to generate a small library of propargylamines 126 using CuBr as the catalyst. The resulting compounds 126 were isolated in good to excellent yields except when n-butylamine was used as amine counterpart and were further converted into Steganacin aza-analogs (Scheme 98). 

The total synthesis of amaryllidaceae alkaloid buflavin was achieved in the laboratory of A. Couture by utilizing a Horner-Wittig reaction between a biaryl aldehyde and a metalated carbamate. The diphenyl phosphine oxide carbamate was deprotonated with n-BuLi. To the resulting metalated carbamate was added the solution of the biaryl aldehyde in THF. The reaction afforded the corresponding (Z)- and ( )-enecarbamates in good yield and with high -selectivity. 

The synthesis of 189 containing substituted biphenyl substituents at C-4 has been reported through a three-component one-pot condensation of biaryl aldehydes 188, p-ketoester and urea/thiourea (Scheme 71) (10JFTC33). 

The Homer-Wadsworth-Emmons (HWE) reaction of a lithiated (diphenylphosphinoyl)methyl amine with a biaryl aldehyde furnishes the corresponding enecarbamates, which serve as key intermediates for the synthesis of the Amaryllidaceae alkaloid buflavine (eq 44). ... 

Macrocyclic furanyl pyrimidine SB1578 (2) was also synthesized via a convergent route using a RCM as the key step, starting from 2,4-dichlorop)T-imidine (99) as shown in Scheme 5.6. Suzuki coupling of 99 with boronic acid 113 proceeded smoothly to furnish biaryl aldehyde 114 in moderate yield followed by reduction in the presence of sodium borohydride to furnish an almost quantitative yield of alcohol 115. Alkylation of benzyl alcohol 115 with allyl bromide 94 under phase transfer conditions provided the key left-hand fragment 116. 

Chiral aluminum catalyst 2, prepared from Et2AlCl and a Vaulted biaryl ligand, is reported to be an effective Lewis acid catalyst of the Diels-AIder reaction between methacrolein and cyclopentadiene, affording the adduct in 97.7% ee [4] (Scheme 1.2). Although the Diels-AIder reaction with other a,/ -unsaturated aldehydes has not been described, that only 0.5 mol% loading is sufficient to promote the reaction is a great advantage of this catalyst. 

Chamoin S, Houldsworth S, Kruse CG, Bakker WI, Snieckus V. The Suzuki-Miyaura cross coupling reactions on solid support. Link to solution phase directed ortho metalation. The Leznoff acetal linker approach to biaryl and heterobiaryl aldehydes. Tetrahedron Lett 1998 39 4179-4182. 

Since ketone R)-16 was prepared in a non-selective way when an achiral imino enolate was alkylated, it was considered whether alkylation of chiral enolates, such as that of oxazoline 18, with benzyl bromide 14, would provide stereoselective access to the corresponding alkylation product 19 with R-configuration at C(8) (Scheme 4). Indeed, alkylation of 18 with 14 gave the biaryl 19 and its diastereoisomer almost quantitatively, in a 14 1 ratio. However, reductive hydrolysis using the sequence 1. MeOTf, 2. NaBH4, and 3. H30", afforded hydroxy aldehyde 20 in 25% yield at best. Furthermore, partial epimerization at C(8) occurred (dr 7.7 1). An alternative route, using chiral hydrazones, was even less successful. 

A simple, commercially available chiral alcohol, a,a,a a -tetraaryl-l,3-dioxo-lane-4,5-dimethanol (TADDOL, 7a), catalyzes the hetero- and carbo-Diels-Alder reactions of aminosiloxydienes with aldehydes and a-substituted acroleins to afford the dihydropyrones and cyclohexenones, respectively, in good yields and high enan-tioselectivities. More recently, it was reported that axially chiral biaryl diols 7b and 7c were more highly effective catalysts for enantioselective hetero-Diels-Alder reactions (Scheme 12.5). ... 

Maruoka has found that simple alcohols can also be used in the oxy-Michael reaction [107], Using the axially chiral biaryl catalyst 67 (1 mol%) the conjugate addition of methanol, ethanol and aUyl alcohol to a, 3-unsaturated aldehydes was examined (Scheme 29). Despite moderate yields (55-83%) and enantioselectivities (16-53% ee), the high activity of this catalyst suggests that further optimisation... 

A biaryl propionic acid derivative containing a furan ring as a prominent feature has antiinflammatory activity. The patented synthesis involves a straightforward organometallic addition of ethyl lithioacetate to aldehyde 12 followed by saponification... 

The lactone concept is not restricted to the simple model biaryl synthesis presented here. It has been successfully expanded to a broad series of structurally diverse biaryl substrates (e.g., lactones with additional stereocenters and functional groups, configurationally stable lactones, seven-membered lactones, and again configurationally unstable biaryl hydroxy aldehydes ), to different activation modes in the ring-opening step (e.g., use of metallated nucleophiles, carbonyl activation by Lewis acids, (Ti -complexation, etc.), and for various strategies of stereoselection (e.g., external vs. internal asymmetric induction). ... 

Chamoin, S. Houldsworth, S. Kruse, C. G. Bakker, W. I. Snieckus, V. The Suzuki-Miyaura Cross Coupling Reactions on Solid Support. Link to Solution Phase Directed ortho Metalation. The Leznoff Acetal Linker Approach to Biaryl and Heterobiaryl Aldehydes, Tetrahedron Lett. 1998, 39, 4179-4182. 

SYNTHESIS OF UNSYMMETRICAL BIARYLS USING A MODIFIED SUZUKI CROSS-COUPLING 4-BIPHENYLCAR BOX ALDEHYDE ([1,1 -Biphenyl]-4-carboxaldehyde)... 

Here the substrates are 3-silyloxy-l,5-enynes the concept was to combine a metal-induced 6-endo-trig cyclization with a ring contraction by a sigmatropic rearrangement (Scheme 12.12).27 From the cationic intermediate, elimination to the biaryl product can be observed in addition to the aldehyde. 

D. The use of chiral oxazaborolidines as enantioselective catalysts for the reduction of prochiral ketones, imines, and oximes, the reduction of 2-pyranones to afford chiral biaryls, the addition of diethylzinc to aldehydes, the asymmetric hydroboration, the Diels-Alder reaction, and the aldol reaction has recently been reviewed.15b d The yield and enantioselectivity of reductions using stoichiometric or catalytic amounts of the oxazaborolidine-borane complex are equal to or greater than those obtained using the free oxazaborolidine.13 The above procedure demonstrates the catalytic use of the oxazaborolidine-borane complex for the enantioselective reduction of 1-indanone. The enantiomeric purity of the crude product is 97.8%. A... 

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