Vinylogous Mukaiyama

As an extension of this work, these authors have applied this catalyst system to vinylogous asymmetric Mukaiyama-type aldol reactions, involving silyl vinyl ketene acetals and pyruvate esters. These reactions afforded the corresponding y,5-unsaturated a-hydroxy diesters with quaternary centres in high yields and enantioselectivities of up to 99% ee (Scheme 10.25). It was shown that the presence of CF3CH2OH as an additive facilitated the turnover of the catalyst. 

Scheme 10.25 Cu-catalysed vinylogous Mukaiyama-type aldol reactions with Ci-S5mmetric benzene-bridged aminosulfoximine ligand.

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

L2909>. An organocatalytic addition of 2-trimethylsilyloxyfuran to aldehydes using 10 mol% of l,3-bis(3-(trifluoromethyl)phenyl)urea provided adducts with modest threo selectivity <06TL8507>. A syn-selective, enantioselective, organocatalytic vinylogous Mukaiyama-Michael addition of 2-trimethylsilyloxyfuran to (E)-3-... 

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 ... 

In regard to the importance of a diastereoselective synthesis of 5-[hydroxy(aryl) methyl]furan-2(5//)-ones, the Bi(OTf)3-4H20-catalyzed vinylogous Mukaiyama aldol has been investigated with 2-(trimethylsilyloxy)furans and various carbonyl compounds [146]. 

Table 16 Vinylogous Bi(OTf)3-catalyzed Mukaiyama aldol reactions involving benzaldehyde and 2-(trimethylsilyloxy)furan...

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 Rawal group next applied diol catalysis to the enantioselective vinylogous Mukaiyama aldol (VMA) reaction of electron-deficient aldehydes [105]. Screening of various known chiral diol derivatives, including VANOL, VAPOL, BINOL, BAMOL, and TADDOL, revealed that 38a was the only catalyst capable of providing products in acceptable levels ofenantioselection (Scheme 5.55). Subsequent to this work, Scettri reported a similar study of TADDOL-promoted VMA reactions with Chan s diene [106]. 

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>. 

Mukaiyama-type aldol reactions and vinylogous aldol reactions... 

Campagne and Bluet recently reported the catalytic asymmetric vinylogous Mukaiyama aldol (CAVM) reaction of aldehydes with dienol silyl ether 15 using chiral ammonium fluorides as an activator. For example, the CAVM reaction of isobutyr-aldehyde with 15 in the presence of 10 mol% of 4b in THF at room temperature led to the formation of the vinylogous aldol product 16 in 70% yield with 20% ee. The ee-value was improved to 30% by conducting the reaction at 0 °C (Scheme 9.6) [16]. 

Chiral sulfoximines liganded to copper(II) give highly enantioselective vinylogous Mukaiyama-type aldol reactions under mild conditions.137 A chiral sulfinyl group has been used to achieve 1,5- and 1,6-asymmetric induction in Mukaiyama aldols, using Yb(OTf)3 catalysis.138... 

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... 

Intermolecular Michael addition [4.1] Intermolecular aldol reaction [6.2.1] Intramolecular aldol reaction [6.2.2] Aldol-related reactions (e.g. vinylogous Mukaiyama-type aldol) [6.2.3]... 

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 catalytic asymmetric vinylogous Mukaiyama reaction between silyl dienolate 896 and aliphatic ketone 897 provides the 5,6-dihydropyran-2-one 898, a key intermediate during a formal synthesis of enantiopure taurospongin A (Equation 361) <2005JA7288>. 

CVAM catalytic asymmetric vinylogous Mukaiyama (reaction)... 

A highly yvn-diastereoselective and enantioselective vinylogous Mukaiyama aldol addition of trimethylsilyloxyfurans to aldehydes was achieved by using a cinchonidine-... 

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