**7. One-pot Wittig-olefination/functional group interconversion**

Wittig reactions can be performed with alkoxycarbonylmethylidenetriphenylphosphorane (**21**) in aq. NaOH, where the cinnamates formed are hydrolysed *in situ* to cinnamic acids **106** (**Scheme 27**) [152]. After completion of the reaction, triphenylphosphine oxide can be filtered off from the strongly basic, aqueous solution, and the cinnamic acids are isolated by simple filtration after acidification of the filtrate. Pinacol-acetal tripropylphosphonium salt **107** has been reacted in aq, 1 M NaOH with different benzaldehydes **37**; the cinnamaldehyde *O*,*O*pinacol acetal can be hydrolyzed directly to the cinnamaldehydes **108** with 25w% aq. H<sup>3</sup> PO<sup>4</sup> (**Scheme 28**) [153].

This procedure provides a nice alternative to the reaction of benzaldehydes with triphenylphosphoranylideneacetaldehyde, which often produces dienals and trienals as side-products. A tandem Wittig-cyanosilylation was developed by Zhou et al., where again Ph<sup>3</sup> PO as side product of the Wittig olefination acts as Lewis base to catalyze TMSCN in the cyanosilylation step. Chiral salen

function induces a cyclization through a Michael reaction. This reaction sequence has been used especially in the construction of functionalized C-glycosides such as in the stereospecific

Tandem-, Domino- and One-Pot Reactions Involving Wittig- and Horner-Wadsworth-Emmons...

http://dx.doi.org/10.5772/intechopen.70364

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In their synthesis to C-glycoside amphiphiles, Ranoux et al. followed a similar strategy, reacting non-protected sugars with HWE reagents in aqueous or solventless conditions, leading to

A different mechanism to C-glucosides operates when 5,6-dideoxy-5,6-anhydro-6-nitro-d-glucofuranose **122** is reacted with an excess of phosphorane **21**. Here, **21** acts as a base and **122** experiences an anion driven ring opening to **123**, which undergoes an oxy-Michael addition to **124** with concomitant Wittig reaction, resulting in C-vinyl glycoside **125** (**Scheme 32**) [156]. A highly stereoselective tandem Wittig-reaction-Michael addition has been developed by Liu et al. [157] when reacting 3-carboxy2-oxopropylidene)triphenylphosphorane **126** with

**Scheme 30.** Synthesis of ω-amino-*β*-d-furanoribosylacetic acid derivative **115** utilizing a Wittig olefination-ring closure

**Scheme 31.** Synthesis of C-glucosides with a HWE—ring closure reaction.

synthesis of ω-amino-*β*-d-furanoribosylacetic acid derivative **115** (**Scheme 30**) [154].

C-glucosides **117** and **121** (**Scheme 31**) [155].

reaction en route.

**Scheme 27.** One-pot Wittig reaction—ester hydrolysis.

**Scheme 28.** One-pot Wittig reaction—acetal hydrolysis.

aluminum catalyst **109** was used as Lewis acid to activate the keto function in the cyanosilylation. Products were obtained with high enantioselectivity [68–93%ee]. TMSCN and chiral catalyst **109** were added after completion of the Wittig reaction, albeit in one pot (**Scheme 29**) [143].

As Wittig reactions can be carried out in aqueous medium, enzymatic reactions can be integrated into the process (*vide supra*). In this regard, M. Krauβer et al. showed that 4-phenylbut-3-en-2-ones (**93**), obtained by Wittig olefination, are reduced to the corresponding 4-phenylbut-3-en-2-ols (**94**) in >99 ee(%) using (*S*)-alcohol dehydrogenase [(*S*)-ADH] from *Rhodococcus* sp. or (*R*)-ADH from *Lactobacillus kefir* [148].

**Scheme 29.** Wittig reaction—cyanosilylation.
