Aldol coupling reactions

Base for aldol coupling reactions, and tiie syntiiesis of lactone precursors and ketones. ... 

K. L. Yu, S. Handa, R. Tsang, and B. Fraser-Reid, Carbohydrate-derived partners display remarkably high stereoselectivity in aldol coupling reactions, Tetrahedron 47 189 (1991). 

A marked improvement of the enantioselectivity was achieved by Corey and coworkers by using a bifluoride catalyst 4 [5]. Bi fluoride derivatives such as 4 are usually less hygroscopic than monofluorides such as 1 and thus easier to handle. Using catalyst 4 (10 mol%), the silyl enol ethers S reacted with various aliphatic aldehydes smoothly at —70 °C via the aldol coupling reaction to afford the chiral 5-hydroxy-a-amino esters 6 with moderate to good enantioselectivily for the syn adduct (72-89% ee) (Scheme 8.2). However, the diastereoselectiviy varied from 1 1 to 13 1 (syn anti). 

The preparation of the methyl ketone required for the aldol coupling reaction was accomplished by using the asymmetric alkylation of the unsaturated amide 158 according to a protocol developed by Myers [112]. Asymmetric alkylation of 158 with ethyl iodide gave 159 which was reduced to the primary alcohol (LiNH2, BH3) and protected as a PMB ether to produce, after oxidative cleavage of the olefin, the methyl ketone 160 which was converted to the trimethylsilyl enol ether 161 (LiHMDS, TMSC1) (Scheme 31). 

The requisite dihydroxyketones are commonly assembled via iterative aldol coupling reactions [1], but other methods including Nef reactions [17,18], acetylide additions [19, 20], 1,3-dipolar nitrile oxide cycloadditions [21], iterative alkylation of dithianes [22-28], hydrazones [29], oximes [30], nitriles [31], or dihalomethylene species [32-34], cross-metathesis/hydroboration/oxidation [35], iterative substitution of a xanthate [36], dihydroxylation/desymmetrization of alkenes [37], Homer-Wadsworth-Emmons olehnations [38, 39], allylmetallations [40], and alkyne-alkyne cross-coupling [41] have also been reported. 

Hashimoto T, Ito J, Nishiyama H. Felkin-Anh selectivity in Rh(bisoxazolinylphenyl)-catalyzed reductive aldol coupling reaction asymmetric synthesis of stereotriads. Tetrahedron 2008 64 9408-9412. 

Paterson, I. and Oballa, R.M. (1997) Studies in marine macrolide synthesis synthesis of the C-l-C-15 subunit of spongistatin 1 (altohyrtin A) and 15,16-anti aldol coupling reactions. Tetrahedron Lett., 38, 8241-8244. 

Real-time ultrafast 2D NMR observations of an acetal hydrolysis at natural abundance have enabled observation of the reactive hemiacetal intermediate. Mutual kinetic enantioselection (MKE) and enantioselective kinetic resolution (KR) have been explored for aldol coupling reactions of ketal- and dithioketal-protected -ketoaldehydes expected to have high Felkin diastereoface selectivity with a chiral ketone enolate. ... 

The issue of stereochemistry, on the other hand, is more ambiguous. A priori, an aldol condensation between compounds 3 and 4 could proceed with little or no selectivity for a particular aldol dia-stereoisomer. For the desired C-7 epimer (compound 2) to be produced preferentially, the crucial aldol condensation between compounds 3 and 4 would have to exhibit Cram-Felkin-Anh selectivity22 23 (see 3 + 4 - 2, Scheme 9). In light of observations made during the course of Kishi s lasalocid A synthesis,12 there was good reason to believe that the preferred stereochemical course for the projected aldol reaction between intermediates 3 and 4 would be consistent with a Cram-Felkin-Anh model. Thus, on the basis of the lasalocid A precedent, it was anticipated that compound 2 would emerge as the major product from an aldol coupling of intermediates 3 and 4. 

Z-vinyl iodide was obtained by hydroboration and protonolysis of an iodoalkyne. The two major fragments were coupled by a Suzuki reaction at Steps H-l and H-2 between a vinylborane and vinyl iodide to form the C(ll)-C(12) bond. The macrocyclization was done by an aldol addition reaction at Step H-4. The enolate of the C(2) acetate adds to the C(3) aldehyde, creating the C(2)-C(3) bond and also establishing the configuration at C(3). The final steps involve selective deprotonation and oxidation at C(5), deprotection at C(3) and C(7), and epoxidation. 

After the initial two reports of Rh- and Co-catalyzed reductive aldol couplings, further studies did not appear in the literature until the late 1990s. Beyond 1998, several stereoselective and enantioselective reductive aldol reactions were developed, which are catalyzed by a remarkably diverse range of metal complexes, including those based upon Pd, Cu, Ir, and In. In this chapter, transition metal-catalyzed aldol, Michael, and Mannich reactions that proceed via transition metal hydride-promoted conjugate reduction are reviewed. 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

As described above, our synthetic strategy involves the convergent construction of the central cyclopentanone ring with a carbonylative cross-coupling reaction and a photo-Nazarov cyclization reaction (Chart 2.2). The electrophilic coupling component 51 was synthesized by an intramolecular Diels-Alder reaction [34] and the nucleophilic coupling component 52 by a vinyiogous Mukaiyama aldol reaction [35]. 

Dialkyl(trimethylsilyl)phosphines undergo 1,4-addition to a,/3-unsaturated ketones and esters to give phosphine-substituted silyl enol ethers and silyl ketene acetals, respectively. A three-component coupling reaction of a silylphosphine, activated alkenes, and aldehydes in the presence of a catalytic amount of GsF affords an aldol product (Scheme 76).290 291... 

---