Aldol reactions vinylogous Mukaiyama

A Lewis acid-catalyzed vinylogous Mukaiyama aldol reaction between 2-trialkylsilyloxyfurans and a-substituted ketones proceeded diastereoselectively... 

Herein we will focus on the recent development of vinylogous [1] aldol reactions and their application in the synthesis of natural products [2-5]. In particular the synthesis of unsaturated esters through the vinylogous Mukaiyama aldol reaction is of great interest, since it provides rapid access to larger carbon frameworks and allows for a wide variety of transformations of the double bond (dihydroxylation, epoxidation, cuprate addition etc.). 

Based on these results, Kalesse et al. applied the vinylogous Mukaiyama aldol reaction in their total synthesis of ratjadone [33, 34]. In the synthesis of the C14-C24 segment (A-fragment), the vinylogous aldol reaction was used together with different Lewis acids to achieve the addition of this diacetate syn-thon in a diastereoselective manner under Felkin control (Scheme 23). 

Table 12 Vinylogous Mukaiyama aldol reaction using different Lewis acids... 

Scheme 26 Vinylogous Mukaiyama aldol reaction using y-substituted ketene acetals...

In two studies toward the total synthesis of natural products it could be shown that the a,jS-unsaturated esters derived from the vinylogous Mukaiyama aldol reactions can be further functionalized into advanced intermediates. The C1-C7 segment of oleandolide commences with the VMAR of aldehyde 68 derived from the Roche ester. The so-generated stereo-triad was protected as PMB ether and the ester 76 was reduced to the allylic alcohol. Sharpless asym-... 

Using chiral catalysts, not only various enantioselective Mukaiyama and vinylogous Mukaiyama aldol reactions have been developed but also asymmetric reactions of a,a-difluoro silyl enol ethers (1) with carbonyl compounds have been reported ... 

Table 19 Bi(OTf)3-catalyzed vinylogous Mukaiyama aldol reaction of benzaldehyde...

Table 20 0 Ah Bi(OTf)3-catalyzed vinylogous Mukaiyama aldol reaction of 1. 1 mol % Bi(0Tf)3-4H20 j Et20,-78° C, 1-2 h various aldehydes v HO O X) 31...

The asymmetric vinylogous Mukaiyama aldol reaction was applied in several natural product syntheses, such as macquarimicins <2003JA14722, 2004JA11254>, leucascandrolide A <2002AGE4098, 2003JOC9274>, and dactylo-lide <2005AGE3485>. 

To start with the addition of y-dienolates to aldehydes, the so-called vinylogous Mukaiyama aldol reaction, Campagne et al. studied the applicability of different types of catalyst when using the silyldienolate 115 as nucleophile [121]. In general, many products obtained by means of this type of reaction are of interest in the total synthesis of natural products. It should be added that use of CuF-(S)-TolBinap (10 mol%) as metal-based catalyst led to 68% yield and enantioselectivity up to... 

A range of chiral pre-organized diols have been studied to assess their potential to catalyse vinylogous Mukaiyama aldol reactions enantioselectively via hydrogen bonds.141... 

The vinylogous Mukaiyama aldol reaction of 2-(TMS-oxy)furans with methacro-leins, catalysed by boron trifluoride etherate, has been studied experimentally and computationally, to identify the factors behind observed diastereoselectivities.143... 

A ternary chelate of TiCU, sparteine and the A-acetyl derivative of the tricyclic thiazoli-dinethione 74 acts as a chiral donor in aldol reaction with aldehydes. The tryptophan-derived oxazaborolidinone 75 is serviceable in completing the vinylogous Mukaiyama aldol reaction to furnish chiral products. ... 

For a review on the vinylogous Mukaiyama aldol reactions G. Casiraghi, L. Battistini, C. Curti, G. Rassu and F. Zanardi, Chem. Rev., 2011, 111, 3076. 

In 2008, Barrett et al. reported on a biomimetic synthesis of (,S)-zearalenone involving a late-stage aromatization (373). They started with the synthesis of the two building blocks 505 and 509 (Scheme 9.4). The enantiopure alcohol 505 was prepared in five steps from ( )-5-hexanolide (502) by applying a Upase-mediated strategy. Dioxinone 509 was synthesized using a vinylogous Mukaiyama aldol reaction to link aldehyde 506 with olefin 507. 

A silver salt dramatically reverses the diastereoselectivity of a titanium-chloride-mediated vinylogous Mukaiyama aldol reaction of a chiral vinylketene silyl N, 0-acetal with ethyl glyoxolate. ° ... 

The synthesis of the carboxylic acid 9a commenced with silylation of known alcohol 16 followed by reductive removal of the chiral auxiliary to give the aldehyde 17 (Scheme 3). Vinylogous Mukaiyama aldol reaction" " of 17 with Chan s diene 18" afforded the alcohol 19 in 95% yield with 10 1 diastereoselectivity. Treatment of 19 with PPTS in MeOH resulted in cleavage of the silyl ether and spontaneous methyl acetalization to provide the methyl acetal 20. Protection of the hydroxyl group of 20 by using MPM trichloroacetimidate in the presence of La(OTf >3" gave the MPM ether 21. Hydrolysis of the methyl ester of 21 afforded the carboxylic acid 9a. 

Scheme 2.27 Synthesis of dihydropyrones via asymmetric, vinylogous Mukaiyama aldol reactions (TBAT, tetra-n-butylammonium difluorotriphenylsiliconate).

Curti C, Ranieri B, Battistini L, Rassu G, Zambrano V, Pelosi G, Casiraghi G, Zanardi F (2010) Catalytic, asymmetric vinylogous mukaiyama aldol reactions of pyrrole- and furan-based dienoxy silanes how the diene heteroatom impacts stereocontrol. Adv Synth Catal 352 2011-2022... 

SCHEME 52 Regioselectivity of the vinylogous Mukaiyama aldol reaction using 2-silyloxyfuran. 

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