**5. One-pot Wittig- and HWE olefination/cycloaddition reaction**

One can easily visualize that an alkene prepared by a Wittig olefination can easily be used as a 2-pi component in cycloaddition reactions, in one pot (**Scheme 10**). A typical such cycloaddition is [4+2]-cycloaddition, such as the classical Diels Alder reaction, which can be performed both inter-[69, 124] and intramolecularly [125–132] in tandem with a Wittig-reaction.

Hilt and Hengst have published a cobalt(I)-catalyzed Diels Alder reaction of alkynyltriphenylphosphonium and 1,3-dienes with a consecutive Wittig reaction of the cycloadduct with

Tandem-, Domino- and One-Pot Reactions Involving Wittig- and Horner-Wadsworth-Emmons... http://dx.doi.org/10.5772/intechopen.70364 11

**Scheme 10.** Oxidation—Wittig-olefination—Diels-Alder reaction sequence.

**4. Wittig- and HWE reactions and C**─**C-coupling reactions in one-pot** 

**5. One-pot Wittig- and HWE olefination/cycloaddition reaction**

**Scheme 9.** One-pot Heck cross-coupling/Wittig reaction.

both inter-[69, 124] and intramolecularly [125–132] in tandem with a Wittig-reaction.

One can easily visualize that an alkene prepared by a Wittig olefination can easily be used as a 2-pi component in cycloaddition reactions, in one pot (**Scheme 10**). A typical such cycloaddition is [4+2]-cycloaddition, such as the classical Diels Alder reaction, which can be performed

Hilt and Hengst have published a cobalt(I)-catalyzed Diels Alder reaction of alkynyltriphenylphosphonium and 1,3-dienes with a consecutive Wittig reaction of the cycloadduct with

Wittig- and Horner-Wadsworth-Emmons reactions can be combined with C─C-coupling reactions such as Suzuki cross-coupling [111–113], Mizoroki-Heck reaction [113–118] and Sonogashira-reaction [119]. Initially, it was observed that conjugated phosphoranes were stable under reaction conditions used for Heck- or Suzuki reactions (**Scheme 9**). Thus, phosphoranes themselves could be functionalized by Suzuki- [120], Mizoroki-Heck- [121], or Sonogashira-type [119] cross-coupling reactions, either in solution or when polymer-bound [122]. These phosphoranes could then be subjected to normal Wittig-olefination reactions with ketones or aldehydes [120–122]. The one-pot Wittig-Heck-reaction strategy can be extended to include an *O*-alkylation, where the Wittig reaction of a *p*-hydroxybenzaldehyde (**43**) with methylenetriphenylphosphorane, obtained *in situ* from phosphonium salt **44** provides the *p*-hydroxystyrene as the olefin component in the Mizoroki-Heck reaction in the presence of an alkyl bromide (e.g., **45**), which *O*-alkylates the phenoxy-function to give alkoxystilbenes

**procedures**

10 Alkenes

**46** (**Scheme 9**) [123].

various aldehydes in one pot that lead after a further dehydrogenative step to substituted stilbenes and styrenes (**Scheme 11**) [133].

Interesting is the cycloaddition of *in situ* produced benzyne (**55**) to 1,4-diphenylbutadiene, prepared *in situ* by HWE reaction from cinnamaldehyde, (**15**) give 1,4-diphenylnaphthalene (**56**) (**Scheme 12**) [134].

The transformation sequence Diels-Alder/Wittig can be part of a more complex reaction chain. Thus, Ramachary and Barbas III [135] have forwarded a Domino Wittig/Knoevenagel/

**Scheme 11.** Cobalt (I)-catalyzed Diels Alder reaction—Wittig reaction.

**Scheme 12.** One-pot HWE reaction**—**cycloaddition of *in situ* produced benzyne.

Diels-Alder sequence to spirotriones **58** (**Scheme 13**) and a Wittig/Knoevenagel/Diels-Alder/ Huisgen cycloaddition sequence to polysubstituted triazoles **61** (**Scheme 14**).

Oxidation of benzyl alcohols to benzaldehydes can be incorporated into a Wittig-Diels Alder sequence [69]. Also, hetero-Diels-Alder reactions can be run in tandem with a Wittig olefination as shown by Ramachary et al. in their synthesis of tetrahydropyrans **64** (**Scheme 15**) [136]. Here, diamine **63** is used as a catalyst. The reaction, however, gives the product only in low enantiomeric excess (**Scheme 15**).

Huisgen type [3+2]-cycloaddition reactions can be run also in a simple tandem process rather than incorporated in a more complex reaction chain (see above). A typical example is shown in **Scheme 16**, where azidoethyl-tetrahydro-hydroxyfuran **66** is treated with phosphorane **21** to give triazoline **68** alongside diazoamine **69** [137]. Further such approaches are known [138, 139].

**6. One-pot Wittig- and HWE olefination/addition reaction**

**Scheme 16.** Wittig reaction**—**intramolecular Huisgen type [3+2]-cycloaddition.

**Scheme 15.** Wittig-reaction/hetero-Diels Alder reaction.

obtained α-CF<sup>3</sup>

Electrophiles can be added to the alkene function obtained, in a one-pot reaction with the Wittig olefination. A typical example is the stereoselective bromination of the Wittig product with oxalyl bromide (**71**), where triphenylphosphine oxide (**70**) as side product of the olefination step acts as a catalyst in the bromination (**Scheme 17**) [140]. Hamza and Blum have developed a sol–gel entrapped tertiary phosphine by co-polycondensation of tetramethoxysilane, 2-diphenyl(phosphino)ethyltri(ethoxy)silane and *N*-2-(aminoethyl)-3-aminopropyltri(methoxy) silane. This could be reacted in a Wittig type olefination with benzyl chlorides (e.g., **76**) and benzaldehydes, prepared *in situ* from benzyl alcohols (e.g., **75**). The strategy allows for the combination of the process with a bromination step in one pot by addition of sol–gel-bound pyridinium hydrobromide perbromide after completion of the Wittig reaction (**Scheme 18**) [71]. Alternatively, the process can be combined with a hydrogenation step by the addition of hydrogen in the presence of an added heterogenized Wilkinson catalyst (**Scheme 19**) [141]. A further Wittig olefination—hydrogenation sequence was developed by Zhou et al. who

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

13


phenylphosphine oxide (again as side product of the Wittig olefination) acts as a Lewis base and activates the silane as hydrogenating agent (**Scheme 20**) [142]. The routine was expanded to other aldehydes including alkanals as educts [143]. This reaction was also carried out with

**Scheme 13.** Domino Wittig/Knoevenagel/Diels-Alder sequence.

**Scheme 14.** Wittig/Knoevenagel/Diels-Alder/Huisgen cycloaddition sequence.

Tandem-, Domino- and One-Pot Reactions Involving Wittig- and Horner-Wadsworth-Emmons... http://dx.doi.org/10.5772/intechopen.70364 13

**Scheme 15.** Wittig-reaction/hetero-Diels Alder reaction.

Diels-Alder sequence to spirotriones **58** (**Scheme 13**) and a Wittig/Knoevenagel/Diels-Alder/

Oxidation of benzyl alcohols to benzaldehydes can be incorporated into a Wittig-Diels Alder sequence [69]. Also, hetero-Diels-Alder reactions can be run in tandem with a Wittig olefination as shown by Ramachary et al. in their synthesis of tetrahydropyrans **64** (**Scheme 15**) [136]. Here, diamine **63** is used as a catalyst. The reaction, however, gives the product only in low enantio-

Huisgen type [3+2]-cycloaddition reactions can be run also in a simple tandem process rather than incorporated in a more complex reaction chain (see above). A typical example is shown in **Scheme 16**, where azidoethyl-tetrahydro-hydroxyfuran **66** is treated with phosphorane **21** to give triazoline **68** alongside diazoamine **69** [137]. Further such approaches are

Huisgen cycloaddition sequence to polysubstituted triazoles **61** (**Scheme 14**).

meric excess (**Scheme 15**).

**Scheme 13.** Domino Wittig/Knoevenagel/Diels-Alder sequence.

**Scheme 14.** Wittig/Knoevenagel/Diels-Alder/Huisgen cycloaddition sequence.

known [138, 139].

12 Alkenes

**Scheme 16.** Wittig reaction**—**intramolecular Huisgen type [3+2]-cycloaddition.
