**1. Introduction**

Gold was long considered to be unsuitable for catalysis due to bulk gold present a high reluctance to react. Nonetheless, in the last part of the 20th century pioneering studies from different groups, showed that gold in oxidation states I and III has a big potential as catalysts specially, in reactions dealing with the activation of C-C multiple bonds [1–7]. Because gold(III) is prone to be reduced, the majority of gold catalyzed transformations described so far involves gold(I) complexes. It has been evidenced that gold(I) is able to trigger the building of complex molecular frameworks in a few steps, under soft conditions and with a high degree of functional group tolerance [8–15]. Its special properties lay on relativistic effects, that contract its 6 s and 6p orbitals and expands the 5d shell, lowering the energy level of the LUMO which in turn is traduced in a high Lewis acidity [16]. The development of unsymmetric transformations with gold(I), was hampered at the beginning because of its preferred linear coordination mode [17, 18], that keeps away the substrate being modified from the chiral ligand environment. Hopefully have been uncovered successful strategies to circumvent this problem, such us the use of chiral counter anions, or the development of suitable chiral ligand incorporating secondary interactions with substrates which achieve high asymmetric level. Conversely gold(III) has an square planar coordination mode, ideal for approaching close together the substrate being transformed and the asymmetric ligand, however as note before, its tendency to be reduced has restricted its applications. A few examples has appeared very recently arriving at a compromise between reactivity an stability and it is expected to continue growing in next years, as the chemistry of gold(III) continues to be enlarge.

This chapter is an overview of the strategies and ligands employed to achieve chiral transformations with gold. It is organized according to the type of ligands designed [19–22].

### **2. Gold(I) asymmetric transformations**

#### **2.1 Gold(I) asymmetric transformations with diphosphine ligands**

The first asymmetric ligands that enabled moderate to good enantiomeric ratios were atropoisomeric bidentate phosphines. The most commons are depicted in **Figure 1**. The importance of these phosphines relay on their relative accessible synthetic procedures and their commercial availability. Along with them, some planar chiral diphosphines, or diphosphines containing asymmetric carbon centers has also been used, although in a minor extent.

One of the reactions more thoroughly studied in gold chemistry is the cycloisomerization of 1,n enynes. Starting from linear pools, this reaction gives access under soft conditions, to otherwise complex synthetic targets. Primary studies over the cycloisomerization of enynes, showed that the alkoxycyclization of 1,6 enynes proceeds with modest values of enantioselectivity using (*S*)-Tol-BINAP as ligand (**Figure 2**, Ec1). It was assumed that the reaction is triggered by a monocationic gold complex, generated *in situ* by halogen abstraction with a silver salt. Upon coordination to the alkyne, the catalyst would promote a 5-*exo-dig* cyclization. As a result, it would be formed a cyclopropyl gold carbene complex, which evolves to the final alkylidene cyclopentene, by nucleophilic attack of methanol to the cyclopropane moiety [23].

#### **Figure 1.**

*Common asymmetric biphosphine ligands.*

**23**

**Figure 3.**

*Asymmetric cyclobutanes synthesis.*

*Gold Catalyzed Asymmetric Transformations DOI: http://dx.doi.org/10.5772/intechopen.97519*

(2.5 mol%) and NaBAr4

E E

1)

2)

3)

F

OEt

R3

R ·

R1 <sup>+</sup> R2

R1 R2

Improved enantiomeric values were obtained in the cycloisomerization of 1,5-enynes bearing cyclopropyliden moieties (**Figure 2**, Ec2). These substrates led to challenging bicyclo[4.2.0]octanes, by a 6-*endo*-*dig* cyclization/ring expansion process [24, 25]. It was observed that the enantioselectivity values were importantly affected by the amount of the silver salt employed. The best results were obtained using the complex (*R,R*)-*i*Pr-DuPHOS(AuCl)2 (5 mol%), and AgNTf (5 mol%) as a silver salt. It could be notice that AgNTf itself, is able to catalyze the reaction in some extension, being responsible of the decrease in the enantiomeric ratios. Related to this ring expansion procedure, 1,6-enynes containing a cycloalkoxy unit, have been shown to rearrangement to cyclopentyl-cyclobutanones with high enantioselectivities, when treated with [(*R*)-MeO-DTBM-BIPHEP-(AuCl)2] (3 mol%) and AgBF4 (6 mol%) [26]. On the other hand, 1-allenylcyclopropanols also undergo a cyclization/ring expansion process that affords chiral vinyl cyclobutanones, with good enantiomeric ratios, when treated with (*R*)-MeO-DTBM-BIPHEP(AuCl)2 (2.5 mol%) and NaBARF (5 mol%) as chloride scavenger. The reaction is promoted by Π activation of the allene through gold coordination, and a subsequent Wagner-Meerwein shift [27]. Finally, another strategy for accessing chiral cyclobutanes consists onto an intermolecular [2 + 2] cycloaddition of alkynes and alkenes. This time higher enationomeric ratios were obtained with a Josiphos digold(I) complex

out in this work, revealed that only one atom of gold is involved in the activation of the alkyne, but the second one is needed to induce enantioselectivity (**Figure 3**) [28]. Chiral cyclopropanes are also amenable with gold complexes by olefin cyclopropanation with diazo compounds (**Figure 4**). Thus, cyclopropanes with vicinal all-carbon quaternary stereocenters can be assembled by reaction of diazooxindoles with α-CH2F styrenes, using a spiroketaldiphosphine digold(I) complex. This reaction benefits from hydrogen bond interaction with the solvent, particularly fluorobencene forms a strong C-F···H-N interaction, that lower the activation barrier of

> wet toluene r.t., 2 h

L = (*R*)-DTBM-SEGPHOS

1,2-DCE, -30 ºC R

NaBAr4

*t*Bu

Fe P


F (2 mol%) L\*(AuCl)2 (2.5 mol%)

1-Napht *t*Bu P

(*S, Rp*)

1-Napht

OH O

NaBARF (5 mol%) L\*(AuCl)2 (2.5 mol%)

24 h

R3

L = (*R*)-MeO-DM-BIPHEP

AgBF4 (6 mol%) L\*(AuCl)2 (3 mol%)

(2.5 mol%). Interestingly, the mechanistic studies carried

R1 O

up to 99% yield up to 94 *ee*

> R2 R3

up to 92% yield up to 98:2 *er*

+

E E

> up to 94% yield up to 99% *ee*

R2

*trans* R3 R1 O

R2 R3

R1

*cis*

E E

E = CO2Me, SO2Ph cis/trans:1.3-40/1

**Figure 2.** *Asymmetric cycloisomerization of 1,6- and 1,5-enynes.*

#### *Gold Catalyzed Asymmetric Transformations DOI: http://dx.doi.org/10.5772/intechopen.97519*

*Current Topics in Chirality - From Chemistry to Biology*

**2. Gold(I) asymmetric transformations**

has also been used, although in a minor extent.

PAr2 PAr2

DuPHOS

P P

R

R

*R*

R

BINAP

designed [19–22].

This chapter is an overview of the strategies and ligands employed to achieve chiral transformations with gold. It is organized according to the type of ligands

The first asymmetric ligands that enabled moderate to good enantiomeric ratios were atropoisomeric bidentate phosphines. The most commons are depicted in **Figure 1**. The importance of these phosphines relay on their relative accessible synthetic procedures and their commercial availability. Along with them, some planar chiral diphosphines, or diphosphines containing asymmetric carbon centers

One of the reactions more thoroughly studied in gold chemistry is the cycloisomerization of 1,n enynes. Starting from linear pools, this reaction gives access under soft conditions, to otherwise complex synthetic targets. Primary studies over the cycloisomerization of enynes, showed that the alkoxycyclization of 1,6 enynes proceeds with modest values of enantioselectivity using (*S*)-Tol-BINAP as ligand (**Figure 2**, Ec1). It was assumed that the reaction is triggered by a monocationic gold complex, generated *in situ* by halogen abstraction with a silver salt. Upon coordination to the alkyne, the catalyst would promote a 5-*exo-dig* cyclization. As a result, it would be formed a cyclopropyl gold carbene complex, which evolves to the final alkylidene cyclopentene, by nucleophilic attack of methanol to the cyclopropane moiety [23].

**2.1 Gold(I) asymmetric transformations with diphosphine ligands**

**22**

**Figure 2.**

**Figure 1.**

PhO2S PhO2S

*Common asymmetric biphosphine ligands.*

2)

1)

MeOH, r.t.

SEGPHOS

PAr2 PAr2 MeO MeO

O O PPh2 Ph2P SKP

O O O O

AgNTf2 (5 mol%) L\*(AuCl)2 (5 mol%)

L = (*R,R*)-*i*Pr-DuPHOS

R2 R1 CH3NO2, 0 ºC, 4 h

*Asymmetric cycloisomerization of 1,6- and 1,5-enynes.*

L\*(AuCl)2 (1.6 mol%)

Ph AgSbF6 (2 mol%) Ph

PhO2S PhO2S

(-) 94% (52% ee)

P(Ar)2 P(Ar)2

Fe P Ar

Ar R P R

Josiphos

BIPHEP

MeOH L = (*S*)-TolBINAP

R1 R2

up to 96% yield up to 85:15 *er*

OMe

LAu

LAu PhO2S Ph PhO2S

coming from a 5-*exo*-*dig cyclization*

R1 R<sup>2</sup>

coming from a 6-*endo-dig cyclization*

Improved enantiomeric values were obtained in the cycloisomerization of 1,5-enynes bearing cyclopropyliden moieties (**Figure 2**, Ec2). These substrates led to challenging bicyclo[4.2.0]octanes, by a 6-*endo*-*dig* cyclization/ring expansion process [24, 25]. It was observed that the enantioselectivity values were importantly affected by the amount of the silver salt employed. The best results were obtained using the complex (*R,R*)-*i*Pr-DuPHOS(AuCl)2 (5 mol%), and AgNTf (5 mol%) as a silver salt. It could be notice that AgNTf itself, is able to catalyze the reaction in some extension, being responsible of the decrease in the enantiomeric ratios. Related to this ring expansion procedure, 1,6-enynes containing a cycloalkoxy unit, have been shown to rearrangement to cyclopentyl-cyclobutanones with high enantioselectivities, when treated with [(*R*)-MeO-DTBM-BIPHEP-(AuCl)2] (3 mol%) and AgBF4 (6 mol%) [26]. On the other hand, 1-allenylcyclopropanols also undergo a cyclization/ring expansion process that affords chiral vinyl cyclobutanones, with good enantiomeric ratios, when treated with (*R*)-MeO-DTBM-BIPHEP(AuCl)2 (2.5 mol%) and NaBARF (5 mol%) as chloride scavenger. The reaction is promoted by Π activation of the allene through gold coordination, and a subsequent Wagner-Meerwein shift [27]. Finally, another strategy for accessing chiral cyclobutanes consists onto an intermolecular [2 + 2] cycloaddition of alkynes and alkenes. This time higher enationomeric ratios were obtained with a Josiphos digold(I) complex (2.5 mol%) and NaBAr4 F (2.5 mol%). Interestingly, the mechanistic studies carried out in this work, revealed that only one atom of gold is involved in the activation of the alkyne, but the second one is needed to induce enantioselectivity (**Figure 3**) [28].

Chiral cyclopropanes are also amenable with gold complexes by olefin cyclopropanation with diazo compounds (**Figure 4**). Thus, cyclopropanes with vicinal all-carbon quaternary stereocenters can be assembled by reaction of diazooxindoles with α-CH2F styrenes, using a spiroketaldiphosphine digold(I) complex. This reaction benefits from hydrogen bond interaction with the solvent, particularly fluorobencene forms a strong C-F···H-N interaction, that lower the activation barrier of

**Figure 3.** *Asymmetric cyclobutanes synthesis.*

the reaction. Yields up to 93% were obtained, with enantioselectivities over 90% and diastereoselectivities higher of 20:1 in all cases [29].

Enantioselective hydroetherification of alkynes is possible by desymmetrization of prochiral phenols containing a P-stereogenic center (**Figure 5**, Ec.1). It has been observed that bisphenols and dialkyne phosphine oxides, undergo a 6-*endodig* cyclization with (*S*)-DTBM-SEGPHOS(AuCl)2 complex, leading to chiral cyclic phosphine oxides. The yields of the reaction maintained up to 97% and the enantioselectivites close to 99%. This reaction is an efficient and practical tool to achieve compounds with P-sterogenic centers [30]. Notably, the same complex has been used for the synthesis of planar-chiral ring*-*fused ferrocenes, starting from *ortho*-alkylnylaryl ferrocenes (**Figure 5**, Ec. 2) [31]. Finally, along with this alkyne activation protocols, (*R*)-DTBM-SEGPHOS(AuCl)2 has been efficiently applied in asymmetric Picted-Spengler reactions between tryptamines and arylaldehydes [32].

### **2.2 Gold(I) asymmetric transformations with monophosphine ligands**

In some reactions catalyzed by chiral digold complexes, better performances were obtained by generation of monocationic instead of dicationic species. This fact points that in those cases the role of the second atom of gold may be just steric, or that it may be involved in secondary interactions with substrates. With this in mind, there has been an increasing interest in developing monophosphine chiral ligands. One of the monophosphines that have exerted better enantioselectivities, are

**Figure 4.** *Asymmetric synthesis of cyclopropanes with diazooxindoles.*

**Figure 5.**

*Asymmetric synthesis of cyclic phosphine oxides, ring-fused planar chiral ferrocenes and tetrahydo-*β*-carbolines.*

**25**

**Figure 6.**

R2 O

1)

R1 O

2)

3)

4)

5)

R3

O PPh2

R2

R1 NTs

N H

R1

R2

<sup>R</sup><sup>2</sup> R2

N TRIS ·

R1

R3

+

N H

L\*/AuCl (5 mol%) NaBArF (10 mol%) 4-F-CF3Ph, -15 ºC

L = (*R*, *Rs*) XIANG-PHOS

Me2SAuCl ( 5mol%) L\* (5.5 mol%) AgNTf2 (5 mol%)

*(1) Synthesis of chiral sulfinamides. (2) Asymmetric reactions with chiral phosphine sulfinamides.*

DCE, -50 ºC, 24 h N

+ R5

H2N <sup>S</sup> O *t*Bu Ti(OPr<sup>i</sup> )4

<sup>N</sup> <sup>R</sup> <sup>O</sup> <sup>4</sup> Me2SAuCl ( 5mol%) L\* (5.5 mol%) AgNTf2 (5 mol%) DCE, -10 ºC

N PPh2

(*Rs*)

<sup>O</sup> *<sup>t</sup>*-Bu

ArLi

ArMgX

Ph

L = (*S*, *Rs*) or (*R*, *Rs*) MING-PHOS

Me2SAuCl ( 5mol%) L\* (5.5 mol%) AgSbF6 (5 mol%)

L = (*S*, *Rs*) MING-PHOS

DCE, -20 ºC, 4Å MS <sup>R</sup> <sup>O</sup> <sup>1</sup> <sup>R</sup><sup>3</sup>

TsN

<sup>H</sup> R1

Up to 99% yield Up to 98% *ee*

> H <sup>N</sup> TRIS R1 <sup>R</sup><sup>2</sup> R2

Up to 99% yield Up to 94% *ee*

O N

NH PPh2

(*S, Rs*)

<sup>O</sup> *<sup>t</sup>*-Bu (*R, Rs*)

NH PPh2

Ar

Ar

<sup>O</sup> *<sup>t</sup>*-Bu

R3 R5 Up to 99% yield

Up to 99% yield Up to 97% *ee*

R2

<sup>N</sup> Ph

Up to 99% *ee*

MING-PHOS

Ar NH <sup>S</sup> <sup>O</sup> *<sup>t</sup>*-Bu

Ar = 1-naphthyl MING-PHOS

L =

Ar NH <sup>S</sup> <sup>O</sup> *<sup>t</sup>*-Bu

Ar = 1-(4-methoxynaphthyl) XIANG-PHOS

L =

L =

PAd2

O HN S Ar

Ar= 4-MeOC6H4

PPh2

*t*-Bu O

PPh2

R O <sup>2</sup> R1

R2

*Gold Catalyzed Asymmetric Transformations DOI: http://dx.doi.org/10.5772/intechopen.97519*

monophosphines bearing a chiral sulfinamide moiety that can stablish secondary interactions with the substrates. These ligands offer the advantage of being easily modified, as they can be modularly synthesized. For example, the MING-PHOS family is synthesized by a two-step sequence (**Figure 6**, Ec1), that consists in the condensation of an arylphoshine aldehyde with chiral *tert*-butylsulfinamide, followed by the stereodivergent addition of RLi or RMgX. This way diasteromeric sulfinamide monophosphines can be isolated. MING-PHOS ligands has been applied over a variety of reactions, thus they have shown to catalyze the enantioselective [3 + 3] cycloaddition of 2-(1-alkynyl)-alk-2-en-1-ones with nitrones (**Figure 6**, Ec. 1). The reaction furnished furo[3,4-*d*] [1,2]oxazines, with high diasteroselectivity (> 20:1) and stereoselectivity. Interestingly, both types of enantiomers could be isolated by using a pair of diasterosisomeric MING-PHOS [33, 34]. Replacing nitrones by 3-stylindoles, cyclopenta[c]furans were obtained with similar values of diastereo- and entioselectivities (**Figure 6**, Ec. 3) [35]. A variation of the MING-PHOS family that incorporates adamantyl groups at the phosphorous atom (XIA-PHOS

*Gold Catalyzed Asymmetric Transformations DOI: http://dx.doi.org/10.5772/intechopen.97519*

*Current Topics in Chirality - From Chemistry to Biology*

and diastereoselectivities higher of 20:1 in all cases [29].

the reaction. Yields up to 93% were obtained, with enantioselectivities over 90%

**2.2 Gold(I) asymmetric transformations with monophosphine ligands**

tolueno, 0 °C, 3-15 h AgSF6 (20 mol%)

L\*(AuCl)2 (10 mol%)

AgNTf2 (20 mol%)

toluene, -20 °C, 24 h

L\*(AuCl)2 (10 mol%)

Fe

L = (*R*)-DTBM-SEGPHOS Up to 93% *ee*

DCM, r.t., 3Å MS AgNTf2 (5.8 mol%) L\*(AuCl)2 (3 mol%)

L = (*R*)-DM-SEGPHOS

*Asymmetric synthesis of cyclic phosphine oxides, ring-fused planar chiral ferrocenes and tetrahydo-*β*-carbolines.*

R

<sup>R</sup> L = (*S*)-DTBM-SEGPHOS

AgOTf (4.0 mol%) L\*(AuCl)2 (4.4 mol%)

(dr > 20:1)

R

P

O HO

<sup>O</sup> 1,4-F2C6H4, 0 ºC,

Up to 95% *ee* L = SKP

O

Ar

N H Ar CH2F

(*R*p)

N H

Up to 97% yield Up to 95% *ee*

Up to 92% yield

R3

<sup>N</sup> Mes

Up to 97% yield Up to 99% *ee*

In some reactions catalyzed by chiral digold complexes, better performances were obtained by generation of monocationic instead of dicationic species. This fact points that in those cases the role of the second atom of gold may be just steric, or that it may be involved in secondary interactions with substrates. With this in mind, there has been an increasing interest in developing monophosphine chiral ligands. One of the monophosphines that have exerted better enantioselectivities, are

Enantioselective hydroetherification of alkynes is possible by desymmetrization of prochiral phenols containing a P-stereogenic center (**Figure 5**, Ec.1). It has been observed that bisphenols and dialkyne phosphine oxides, undergo a 6-*endodig* cyclization with (*S*)-DTBM-SEGPHOS(AuCl)2 complex, leading to chiral cyclic phosphine oxides. The yields of the reaction maintained up to 97% and the enantioselectivites close to 99%. This reaction is an efficient and practical tool to achieve compounds with P-sterogenic centers [30]. Notably, the same complex has been used for the synthesis of planar-chiral ring*-*fused ferrocenes, starting from *ortho*-alkylnylaryl ferrocenes (**Figure 5**, Ec. 2) [31]. Finally, along with this alkyne activation protocols, (*R*)-DTBM-SEGPHOS(AuCl)2 has been efficiently applied in asymmetric Picted-Spengler reactions between tryptamines and arylaldehydes [32].

**24**

**Figure 5.**

Fe

N H

3)

2)

HN

Mes

+ R3CHO

OH

<sup>P</sup> <sup>O</sup>

R

1)

**Figure 4.**

R

OH

N H

N2

<sup>O</sup> <sup>+</sup> Ar

CH2F

Ar

*Asymmetric synthesis of cyclopropanes with diazooxindoles.*

monophosphines bearing a chiral sulfinamide moiety that can stablish secondary interactions with the substrates. These ligands offer the advantage of being easily modified, as they can be modularly synthesized. For example, the MING-PHOS family is synthesized by a two-step sequence (**Figure 6**, Ec1), that consists in the condensation of an arylphoshine aldehyde with chiral *tert*-butylsulfinamide, followed by the stereodivergent addition of RLi or RMgX. This way diasteromeric sulfinamide monophosphines can be isolated. MING-PHOS ligands has been applied over a variety of reactions, thus they have shown to catalyze the enantioselective [3 + 3] cycloaddition of 2-(1-alkynyl)-alk-2-en-1-ones with nitrones (**Figure 6**, Ec. 1). The reaction furnished furo[3,4-*d*] [1,2]oxazines, with high diasteroselectivity (> 20:1) and stereoselectivity. Interestingly, both types of enantiomers could be isolated by using a pair of diasterosisomeric MING-PHOS [33, 34]. Replacing nitrones by 3-stylindoles, cyclopenta[c]furans were obtained with similar values of diastereo- and entioselectivities (**Figure 6**, Ec. 3) [35]. A variation of the MING-PHOS family that incorporates adamantyl groups at the phosphorous atom (XIA-PHOS

**Figure 6.**

*(1) Synthesis of chiral sulfinamides. (2) Asymmetric reactions with chiral phosphine sulfinamides.*

family), has been employed for the synthesis of fused polycycles. Thus, the intramolecular cyclopropanation of indenes or trisubstituted alkenes, led to polycyclic compounds containing two vicinal all-quaternary stereogeneic centers with excellent yields and enantioselectivities (**Figure 6**, Ec. 4) [36]. N-allenamides attached to the indol nuclei could be cyclized to chiral tetrahydrocarbolines, by using PC-PHOS family. This family of ligands combine the well-known Xant-Phos phospine with a chiral sufinamide, affording high levels of entantioselectivity (**Figure 6**, Ec.5).

Along with chiral phosphine sulfinamides, other chiral bifunctional monophosphine ligands have been described. Based on remote cooperative effects, it have been designed axially chiral monophosphines containing a chiral basic center that can stablish secondary interactions with substrates. These types of ligands have been used to obtain asymmetric 2,5-dihydrofurans with excellent values of enantio- and diasteroselectivity, starting from alkynols through isomerization to chiral allenols and subsequent cyclization (**Figure 7**) [37].

Another interesting approach that relays in secondary interactions, consists in the synthesis of phosphines containing a biphenyl scaffold connected to a C2-chiral pyrrolidine moiety (**Figure 8**). Because of the bulky substituents at the phosporous atom, upon complexation, the P-Au-Cl axis remains parallel to the biphenyl moiety, approaching the gold center to the asymmetric unit. This way it is created a chiral pocket in which the substrate is encapsulated. These ligands have been applied to the cyclization of 1,6-enynes, giving rise to high enantiomeric ratios. DFT calculations showed that the enatioselectivity of the reaction, relays on π-π interactions between the substrate and the ligand. It could be observed opposite enantioselectivities, depending on the position of the aromatic ring in the substrate being cyclized. This chemistry has been applied to the total synthesis of tree members of the carexane family [38].

Finally, phosphahelicenes has also been used to induce asymmetry in the cyclization of 1,6-enynes. These ligands contain a menthyl at phosphorous as the chiral auxiliar. The phosphorous atom racemize at room temperature, and after complexation with a LAuCl precursor, are obtained two epimeric gold complexes; one where the gold atom is disposed toward the helical scaffold (*endo* complex) and another where the gold atom is disposed on the opposite face (*exo* complex). *Endo* isomers give higher enantioselective values since locate closer the metal to the helical moiety (**Figure 9**) [39].

*Asymmetric synthesis of dihydrofuranes with axially chiral bifunctional monophosphines.*

**27**

**Figure 10.**

*Gold Catalyzed Asymmetric Transformations DOI: http://dx.doi.org/10.5772/intechopen.97519*

> MeO2C MeO2C

*Asymmetric cyclization of 1,6-enynes with phosphahelicenes.*

**Figure 9.**

X

X

X

1)

*n*

· R R'

X = C(CO2R)2, NR, O *n* = 1,2

·

·

R

X = C(CO2R)2, C(SO2Ph)2, NR

R

X = C(CO2R)2, C(SO2Ph)2, NR

L\*AuCl/AgSbF6 (10 mol%) DCM, -15 ºC to r.t. <sup>X</sup>

L\*AuCl/AgBF4 (5 mol%) DCM, 25 ºC <sup>X</sup>

L\*AuCl/AgBF4 (5 mol%) DCM, 25 ºC

3) L =

L =

2) L =

*n*

R R'

(4+3) <sup>X</sup>

Ph Ph H Au R' R X

1,2-H shift

ring contraction

Ph Ph

X

*<sup>n</sup>*H

R R' H

Up to 75% yield Up to 85% *ee*

R' R

X

H*<sup>n</sup>* R, R'= Alkyl

*<sup>n</sup>*H

H

R' R

R'= H

*<sup>n</sup>*H

O <sup>O</sup> <sup>P</sup>

O <sup>O</sup> MeO MeO

P Ph

Ph

R = *t*-Bu

<sup>R</sup> <sup>R</sup>

<sup>R</sup> <sup>R</sup>

[Au]

O <sup>O</sup> <sup>P</sup> <sup>N</sup>

H

X H

H R Up to 86% yield Up to 97% *ee*

H R Up to 98% yield Up to 99% *ee*

*Asymmetric cyclization of allendienes and allenenes with BINOL and TADDOL-derived phosphoroamidites.*

Ar

**2.3 Gold(I) asymmetric transformations with phosphoroamidites**

Phosphoroamidites are modulable monodentate ligands that exerts good levels of enantiomeric ratios in gold catalysis. The firsts example of asymmetric transformations employing phosphoramidites, where applied to the cyclization of allenes. Using phoshoroamidite ligands based on BINOL scaffold, it was shown that allenedienes undergo a formal (4 + 3) cycloaddition reaction leading to bicyclic compounds via an allylic cation. The carbene derived from this cation, can evolve via a 1,2-H migration shift, affording 5,7-fused bicyclic compounds, or by a ring contraction leading to 6,7-fused bicyclic compounds. The presence of substituents at the end of the allene favors the formation of 6,7-fused bicyclic compounds. The reaction is totally diastereselective and proceeds with high values of enantioselectivity (**Figure 10**, Ec. 1) [40]. Other BINOL derived ligands have been used in the

S

L =

R

toluene, 20 ºC, 24 h AgBF4 (8 mol%)

P

L\*AuCl (4 mol%) MeO2C

*n*Pr *n*Pr

MeO2C

\*Men 99% yield, 91% *ee*

<sup>S</sup> <sup>S</sup>

n-Pr n-Pr

R = C CPh

*Gold Catalyzed Asymmetric Transformations DOI: http://dx.doi.org/10.5772/intechopen.97519*

*Current Topics in Chirality - From Chemistry to Biology*

allenols and subsequent cyclization (**Figure 7**) [37].

the carexane family [38].

(**Figure 9**) [39].

MeO2C MeO2C

R1

R1 R2 OH

> DCE, 24 ºC, 12-14 h AgPF6 (4 mol%) L\*AuCl (4 mol%) MeO2C

*Asymmetric synthesis of dihydrofuranes with axially chiral bifunctional monophosphines.*

1,2-DCE, 60-80 ºC 2- 24 h

4 (20 mol%) L\*AuCl (5 mol%)

NaBAr<sup>F</sup>

*Asymmetric cyclization of 1,6enynes with biphenyl C2 chiral pyrrolidine phosphines.*

R

R3

MeO2C

R1 Up to 98% yield Up to 96:4 % *er*

O R3

Up to 93% yield Up to 95:5 *er* Up *to 98:2 d.r.*

R1 R2

> P Ad Ad

CF3

L =

L =

Ar = 3,5(CF3)2C6H3

N PAd2

Cy

N Ar Ar

H

family), has been employed for the synthesis of fused polycycles. Thus, the intramolecular cyclopropanation of indenes or trisubstituted alkenes, led to polycyclic compounds containing two vicinal all-quaternary stereogeneic centers with excellent yields and enantioselectivities (**Figure 6**, Ec. 4) [36]. N-allenamides attached to the indol nuclei could be cyclized to chiral tetrahydrocarbolines, by using PC-PHOS family. This family of ligands combine the well-known Xant-Phos phospine with a chiral sufinamide, affording high levels of entantioselectivity (**Figure 6**, Ec.5).

Along with chiral phosphine sulfinamides, other chiral bifunctional monophosphine ligands have been described. Based on remote cooperative effects, it have been designed axially chiral monophosphines containing a chiral basic center that can stablish secondary interactions with substrates. These types of ligands have been used to obtain asymmetric 2,5-dihydrofurans with excellent values of enantio- and diasteroselectivity, starting from alkynols through isomerization to chiral

Another interesting approach that relays in secondary interactions, consists in the synthesis of phosphines containing a biphenyl scaffold connected to a C2-chiral pyrrolidine moiety (**Figure 8**). Because of the bulky substituents at the phosporous atom, upon complexation, the P-Au-Cl axis remains parallel to the biphenyl moiety, approaching the gold center to the asymmetric unit. This way it is created a chiral pocket in which the substrate is encapsulated. These ligands have been applied to the cyclization of 1,6-enynes, giving rise to high enantiomeric ratios. DFT calculations showed that the enatioselectivity of the reaction, relays on π-π interactions between the substrate and the ligand. It could be observed opposite enantioselectivities, depending on the position of the aromatic ring in the substrate being cyclized. This chemistry has been applied to the total synthesis of tree members of

Finally, phosphahelicenes has also been used to induce asymmetry in the cyclization of 1,6-enynes. These ligands contain a menthyl at phosphorous as the chiral auxiliar. The phosphorous atom racemize at room temperature, and after complexation with a LAuCl precursor, are obtained two epimeric gold complexes; one where the gold atom is disposed toward the helical scaffold (*endo* complex) and another where the gold atom is disposed on the opposite face (*exo* complex). *Endo* isomers give higher enantioselective values since locate closer the metal to the helical moiety

**26**

**Figure 8.**

**Figure 7.**

**Figure 9.** *Asymmetric cyclization of 1,6-enynes with phosphahelicenes.*

#### **2.3 Gold(I) asymmetric transformations with phosphoroamidites**

Phosphoroamidites are modulable monodentate ligands that exerts good levels of enantiomeric ratios in gold catalysis. The firsts example of asymmetric transformations employing phosphoramidites, where applied to the cyclization of allenes. Using phoshoroamidite ligands based on BINOL scaffold, it was shown that allenedienes undergo a formal (4 + 3) cycloaddition reaction leading to bicyclic compounds via an allylic cation. The carbene derived from this cation, can evolve via a 1,2-H migration shift, affording 5,7-fused bicyclic compounds, or by a ring contraction leading to 6,7-fused bicyclic compounds. The presence of substituents at the end of the allene favors the formation of 6,7-fused bicyclic compounds. The reaction is totally diastereselective and proceeds with high values of enantioselectivity (**Figure 10**, Ec. 1) [40]. Other BINOL derived ligands have been used in the

#### **Figure 10.**

*Asymmetric cyclization of allendienes and allenenes with BINOL and TADDOL-derived phosphoroamidites.*

cyclization of allenes. Thus, it has been shown that, allenenes undergo a (2 + 2) cycloaddition reaction furnishing 5 + 4 bicyclic compounds with excellent enantioselective values (**Figure 10**, E. 2) [41]. Along with BINOL, TADDOL-derived phosphoramidites has shown excellent performance in asymmetric reactions catalyzed by gold. This scaffold creates a conic cavity of C3 symmetry around the gold center. One of the better TADDOL-derived phosphroamidites bears an acyclic backbone. This type of ligands exerts excellent values of enantioselectivity in a variety of gold catalyzed reactions, in particular allenenes undergo a (2 + 2) cycloaddition reaction with excellent levels of asymmetry [42].

After these initial examples, BINOL derived phosphoroamidites have been used in several relevant organic reactions, such as hetero-Diels-Alder reactions (**Figure 11**, Ec. 1), where the chiral gold(I) complex acts as a Lewis acid activating urea-based diazene dienophiles (**Figure 11**, Ec.1) [43], or in the (3 + 2) annulation of 2-(1-alkynyl)-2-alken-1-ones with *N*-allenamides (**Figure 11**, Ec. 2) [44]. This reaction is proposed to procceds by generation of an all-carbon 1,3-dipole and subsequent (3 + 2) annulation at the proximal C=C bond of the alleneamide.

Looking for more electrophilic phosphorous centers, recently TADDOL and BINOL have been used as chiral scaffolds in α-cationic phosphonites. These ligands incorporate an imidazolium, or a related cationic heterocyclic moiety, directly bounded to phosphorous. The cationic group increase the Lewis acidity character of the phosphorous increasing the activity of gold upon complexation. By far, these ligands have been used for the synthesis of helicenes via gold catalyzed alkyne hydroarylation reactions, with excelents levels of enantioselectivity (**Figure 12**) [45, 46].

#### **2.4 Gold(I) asymmetric transformations with carbenes**

Although in a minor extent than phosphine and phosphoramidites ligands, both acyclic and cyclic N-heterocyclic carbenes have been used in asymmetric gold catalyzed reactions. Acyclic diaminocarbene ligands with a pendant binaphthyl moiety, induce high enantioselective values in gold catalyzed acetalization/cycloisomerization reactions of *ortho*-alkynylbenzaldehydes (**Figure 13**, Ec. 1) [47]. According to DFT calculations, the wide N-C-N angle of the carbene, approaches the binaphthyl unit to the gold center, facilitating an Au-arene interaction, that creates the chiral environment for the enantio-discrimination. N-heterocyclic carbenes (NHC) have

**29**

*Gold Catalyzed Asymmetric Transformations DOI: http://dx.doi.org/10.5772/intechopen.97519*

R1

R2

L\*AuCl/AgSbF6 (10 mol%) FC6H5, -20 ºC 96 h

R2 <sup>R</sup><sup>1</sup>

R2

O P O Ar Ar

MeO SbF6

Ar

Mes

Mes

R'= (*S*)-MePhCH R = 3,5-(CF3)2C6H3

 L = (a*R*, *R*) 87% yield, 73% *ee* L = (a*S*, *R*) 91% yield, -77% *ee*

O <sup>O</sup> <sup>P</sup> N N Me Me

Ar

Ar = 2-Pyrenyl

R H N N R' R'

L =

Mes


Ar Ar

MeO

L =

Up to 98% yield Up to 99% *ee*

Up to 91% yield Up to 98% *ee*

> O OR2

Up to 87% yield Up to 99% *ee*

> <sup>N</sup> <sup>N</sup> DIPP Au N CyR

MeO2C

chiral steric congestion

a*S* δ R1

Ph Ph

R2

L = Ar Ar

L\*AuCl/AgSbF6 (5 mol%) DCM, -10 ºC 24-48 h

DCE, r.t., 12-36 h LiNTf2 (4.5 mol%) L\*AuCl (5 mol%)

NaBAR<sup>F</sup>

DCM (0.1 M), r.t., 48 h

4 (40 mol%) L\*AuCl (5 mol%)

<sup>N</sup> <sup>N</sup> DIPP Au N Cy R

asymmetric electrostatic attraction

R2

R1

*Asymmetric synthesis of helices with* α*-cationic phosphonites*

+ R2-OH

a*R* δ

*Asymmetric transformations with carbene ligands.*

+ Ph

H O

Ph CO2Me N2

R1

1)

2)

**Figure 12.**

1)

2)

**Figure 13.**

been used in bifunctional type ligands containing chiral tetrahydroisoquinoline structures. These ligands contain a fluxional biaryl axis, that allow the aryl groups to be orientated orthogonally. After complexation with AuCl·SMe2, it was possible to separate two atropoisomer complexes generated, due to the restricted rotation of the biaryl axis in the presence of AuCl. It was observed, that each atropoisomers give rise to opposite enantiomers, as it is illustrated in the cyclopropanation of styrene (**Figure 13**, Ec. 2). In the complex with (a*R*,*R*) configuration, the enantiodiscrimination come from an electrostatic attraction effect, between the partially negatively charged ligand nitrogen and the cationic gold center. On the other hand, in the case of the complex with a (a*S*,*R*) configuration, enantio discrimination was attributed to the chiral steric environment posed by the cyclohexyl group [48]. Along with these examples, gold complexes encapsulated in capped cyclodextrin cavities have also shown to catalyze several asymmetric transformations, such us the cycloisomerization of enynes, hydroarylation and lactonizations reactions [49].

**Figure 11.** *(4 + 2) and (3 + 2) cyclizations with BINOL-derived phosphoramidites.*

*Gold Catalyzed Asymmetric Transformations DOI: http://dx.doi.org/10.5772/intechopen.97519*

*Current Topics in Chirality - From Chemistry to Biology*

addition reaction with excellent levels of asymmetry [42].

with excelents levels of enantioselectivity (**Figure 12**) [45, 46].

toluene, -78 ºC L\*AuNTf2 (5 mol%)

> DCM, -15 ºC, 12-24 h AgSbF6 (5 mol%) L\*AuCl (5 mol%) R<sup>3</sup>

R O <sup>1</sup> R2 [Au] R3 N\*

**2.4 Gold(I) asymmetric transformations with carbenes**

cyclization of allenes. Thus, it has been shown that, allenenes undergo a (2 + 2) cycloaddition reaction furnishing 5 + 4 bicyclic compounds with excellent enantioselective values (**Figure 10**, E. 2) [41]. Along with BINOL, TADDOL-derived phosphoramidites has shown excellent performance in asymmetric reactions catalyzed by gold. This scaffold creates a conic cavity of C3 symmetry around the gold center. One of the better TADDOL-derived phosphroamidites bears an acyclic backbone. This type of ligands exerts excellent values of enantioselectivity in a variety of gold catalyzed reactions, in particular allenenes undergo a (2 + 2) cyclo-

After these initial examples, BINOL derived phosphoroamidites have been used in several relevant organic reactions, such as hetero-Diels-Alder reactions (**Figure 11**, Ec. 1), where the chiral gold(I) complex acts as a Lewis acid activating urea-based diazene dienophiles (**Figure 11**, Ec.1) [43], or in the (3 + 2) annulation of 2-(1-alkynyl)-2-alken-1-ones with *N*-allenamides (**Figure 11**, Ec. 2) [44]. This reaction is proposed to procceds by generation of an all-carbon 1,3-dipole and subsequent (3 + 2) annulation at the proximal C=C bond of the alleneamide.

Looking for more electrophilic phosphorous centers, recently TADDOL and BINOL have been used as chiral scaffolds in α-cationic phosphonites. These ligands incorporate an imidazolium, or a related cationic heterocyclic moiety, directly bounded to phosphorous. The cationic group increase the Lewis acidity character of the phosphorous increasing the activity of gold upon complexation. By far, these ligands have been used for the synthesis of helicenes via gold catalyzed alkyne hydroarylation reactions,

Although in a minor extent than phosphine and phosphoramidites ligands, both acyclic and cyclic N-heterocyclic carbenes have been used in asymmetric gold catalyzed reactions. Acyclic diaminocarbene ligands with a pendant binaphthyl moiety, induce high enantioselective values in gold catalyzed acetalization/cycloisomerization reactions of *ortho*-alkynylbenzaldehydes (**Figure 13**, Ec. 1) [47]. According to DFT calculations, the wide N-C-N angle of the carbene, approaches the binaphthyl unit to the gold center, facilitating an Au-arene interaction, that creates the chiral environment for the enantio-discrimination. N-heterocyclic carbenes (NHC) have

> N N FG

R

Up to 99% yield Up to 99% *ee* Up *to 20>*1 *r.r.*

R O <sup>1</sup> R2

Up to 98% yield Up to 95% *ee*

*or* <sup>N</sup> N FG

R3

N Ts Ph

R1

R2 Boc

R

L =

O <sup>O</sup> <sup>P</sup> <sup>N</sup>

Ar Ar = 9-anthracenyl

Ar

Ph Ph

R1

R<sup>2</sup> Boc

R3

**28**

**Figure 11.**

R3 R2 R1

1)

R1

2)

FG

+ N

R3

R O <sup>2</sup>

Boc

N R O

> N Ph Ts

R O <sup>1</sup> R2 [Au] R3 · N\*

*(4 + 2) and (3 + 2) cyclizations with BINOL-derived phosphoramidites.*

R = 4-ClC6H4NH

<sup>+</sup> ·

**Figure 13.** *Asymmetric transformations with carbene ligands.*

been used in bifunctional type ligands containing chiral tetrahydroisoquinoline structures. These ligands contain a fluxional biaryl axis, that allow the aryl groups to be orientated orthogonally. After complexation with AuCl·SMe2, it was possible to separate two atropoisomer complexes generated, due to the restricted rotation of the biaryl axis in the presence of AuCl. It was observed, that each atropoisomers give rise to opposite enantiomers, as it is illustrated in the cyclopropanation of styrene (**Figure 13**, Ec. 2). In the complex with (a*R*,*R*) configuration, the enantiodiscrimination come from an electrostatic attraction effect, between the partially negatively charged ligand nitrogen and the cationic gold center. On the other hand, in the case of the complex with a (a*S*,*R*) configuration, enantio discrimination was attributed to the chiral steric environment posed by the cyclohexyl group [48]. Along with these examples, gold complexes encapsulated in capped cyclodextrin cavities have also shown to catalyze several asymmetric transformations, such us the cycloisomerization of enynes, hydroarylation and lactonizations reactions [49].

#### **2.5 Gold(I) asymmetric transformations with chiral counteranions**

The difficulty in creating an asymmetric environment around gold(I), and the cationic nature of gold(I) catalyzed reactions, led to the search of alternatives strategies to induce asymmetry based on ion pairing. Generation of cationic achiral gold complexes, in the presence of chiral counterions, allow inducing asymmetry by transferring the chiral information via formation of tight ion pairs between cationic organogold species and chiral anions. It was first observed, that allenes undergo hydroalkoxylation, hydrocarboxylation and hydroamination reactions with high enantioselective values, using an achiral diphosphine digold complex in the presence of a chiral silver phosphate derived from binaphthol (**Figure 14**, Ec. 1). It was proposed that, the silver phosphate generates a cationic gold(I) complex leaving the chiral phosphate as counteranion, which is responsible for the enantioselectivity observed [50]. The same strategy was applied to the desymmetrization of 1,3-diols (**Figure 14**, EC. 2) [51].

**Figure 14.** *Asymmetric cyclization of allenes with chiral counterions.*

**31**

biphenol ligand (**Figure 18**) [58].

*Gold Catalyzed Asymmetric Transformations DOI: http://dx.doi.org/10.5772/intechopen.97519*

O Ph

**Figure 16.**

AuL O P <sup>O</sup> <sup>O</sup> O \*

*Asymmetric transformations with phosphoric acid-tethered phosphines.*

<sup>+</sup> HXR<sup>2</sup> L\*AuCl (0.2 mol%) Ag2CO3 (0.1 mol%) toluene, r.t., 16 h

of heteronucleophiles to enones (**Figure 16**) [55].

**3. Gold(III) asymmetric transformations**

The cationic gold(I) specie can also be generated with chiral phosphoric acids by protonolysis of complexes precursors with an Au-Me bond. This type of asymmetric induction has been used in enantioselective transfer hydrogenation reactions of quinolines (**Figure 15**, Ec. 1) [52], in the hydroamination-hydroarylation of alkynes (**Figure 15**, Ec. 2) [53] and in the synthesis of spiroacetals among others [54]. In these approximations the degree of enantio-discrimination depends upon the proximity of the counteranion to the cationic gold center. In this sense, recently have been designed new phosphine ligands, thetered to chiral phosphoric acids, with the aim to restring the flexibility of the ion pair. The new phosphoric acidtethered phosphines have shown excellent levels of enantioselectivity in reactions proceeding through carbocationic intermediates, such us the cyclization-addition

O Ph

Tethered Counterion-Directed Catalysis

> XR<sup>2</sup> Up to 95% yield Up to 91% *ee*

L =

O <sup>O</sup> <sup>P</sup> O OH

Ph2P

Opposite to gold(I), gold(III) complexes have a square-planar geometry that allows ancillary ligands to be closer to the substrate, what made them good candidates for the development of asymmetric transformations. However, its enormous tendency to be reduced, have hampered it use in catalysis. Some recent studies have found the way to stabilize gold(III) centers, while maintaining its catalytic activity, placing them into cyclometalated frameworks. NHC-biphenyl gold(III) complexes with a cyclometalated structure, showed enough stability to catalyze an enantioconvergent kinetic resolution of 1,5-enynes (**Figure 17**, Ec. 1) [56]. In this reaction racemic 1,5-enynes are converted to bicyclo[3.1.0]hexenes with enantiomeric ratios up to 88%. Each enantiomer of the starting 1,5-enyne led to the same bicyclo with different enantioselectivity, making the overall enantioselectivity decrease with the conversion. Because of the latter, the conversions were maintained below, 50%. A related NHC-biphenylene gold(III) catalyst has been applied to enantioselective γ,δ-Diels-Alder reactions. In this occasion enantioselectivities reached 97% and yields were up to 87%. Detailed mechanistic studies revealed that the enantio- discrimination come from non-covalent π-π interactions between the substrate and an aromatic group of the complex (**Figure 17**, Ec. 2) [57]. Other cyclometalated complexes, such as cyclometalated oxazoline gold(III) complexes incorporating a biphenol ligand, have shown to be able to catalyze the asymmetric carboalkoxylation of alkynes. The corresponding 3-alcoxyindanones are obtained with moderate to good enantioselectivities. Remarkably, in this reaction camphorsulonic acid (CSA) activate the gold complex avoiding the need of adding silver salts as activators. Mechanistic studies suggested that the active catalytic specie is formed through protodeauration of one of the oxygens of the

**Figure 15.**

*Asymmetric transformations with chiral phosphoric acids.*

*Gold Catalyzed Asymmetric Transformations DOI: http://dx.doi.org/10.5772/intechopen.97519*

**Figure 16.**

*Current Topics in Chirality - From Chemistry to Biology*

**2.5 Gold(I) asymmetric transformations with chiral counteranions**

applied to the desymmetrization of 1,3-diols (**Figure 14**, EC. 2) [51].

dppm(AuCl)2 (2.5 mol%) (*R*)-AgTRIP (5 mol%) benzene, r.t.

L(AuCl)2 (2.5 mol%) (*R*)-C8-TRIPAg (5 mol%) toluene, 4 Å MS,-10 °C, 24 h

> PAr2 Ar = 3-F-C6H4

PAr2

L =

The difficulty in creating an asymmetric environment around gold(I), and the cationic nature of gold(I) catalyzed reactions, led to the search of alternatives strategies to induce asymmetry based on ion pairing. Generation of cationic achiral gold complexes, in the presence of chiral counterions, allow inducing asymmetry by transferring the chiral information via formation of tight ion pairs between cationic organogold species and chiral anions. It was first observed, that allenes undergo hydroalkoxylation, hydrocarboxylation and hydroamination reactions with high enantioselective values, using an achiral diphosphine digold complex in the presence of a chiral silver phosphate derived from binaphthol (**Figure 14**, Ec. 1). It was proposed that, the silver phosphate generates a cationic gold(I) complex leaving the chiral phosphate as counteranion, which is responsible for the enantioselectivity observed [50]. The same strategy was

> LAuMe (0.01 mol%) PA (0.01 mol%)

> > N N

LAuMe (5 mol%) PA (10 mol%)

LAuMe (5 mol%) PA (5 mol%) toluene, 4 Å MS, r.t. 1-3 h

P(*t*Bu)2

DCE, r.t., 72 h <sup>N</sup>

P(*t*Bu)2

90 °C, 6 - 18h N

H R

Up to 98% *ee* <sup>O</sup>

OH

R1

<sup>O</sup> <sup>P</sup> O OH

Ar

O <sup>O</sup> <sup>P</sup> O OH

Ar PA Ar = 9-anthracenyl

Ar

PA Ar = 2,4,6-*i*Pr3-C6H2

Ar

Up to 99% yield

Y

R3 R3 R2 R2 Up to 97% yield Up to 99% *ee*

R2

C8H17

C8H17

O <sup>O</sup> <sup>P</sup> O O

R

O <sup>O</sup> <sup>P</sup> O O

Ar

Ar

R

(*R*)-TRIP R = 2,4,6-*i*Pr3-C6H2

(*R*)-TRIP Ar = 2,4,6-*i*Pr3-C6H2

R1 R1

R1 HO R2

O

*n*

Up to 95% yield Up to 91% *ee*

R<sup>2</sup> *<sup>n</sup>*

Up to 83% yield Up to 95% *ee*

O O O

NHAr R *<sup>n</sup>* Up to 99% yield Up to 7:1 *dr* Up to 98:2 *er*

Me

**30**

N R

R · <sup>1</sup> R1

1)

2)

R<sup>1</sup> · OH OH

*<sup>n</sup>* R<sup>2</sup> R2

R2 R2 YH R3 R3 Y = O, NSO2Mes

NH2

N Me

OH

2)

3)

**Figure 15.**

1)

**Figure 14.**

+

N H

R1 OH *n* or

+

R *<sup>n</sup>* OH

+ ArNH2 +

OH

*Asymmetric transformations with chiral phosphoric acids.*

L =

Ar

<sup>O</sup> <sup>O</sup> H

L =

L =

EtOOC COOEt

*Asymmetric cyclization of allenes with chiral counterions.*

*Asymmetric transformations with phosphoric acid-tethered phosphines.*

The cationic gold(I) specie can also be generated with chiral phosphoric acids by protonolysis of complexes precursors with an Au-Me bond. This type of asymmetric induction has been used in enantioselective transfer hydrogenation reactions of quinolines (**Figure 15**, Ec. 1) [52], in the hydroamination-hydroarylation of alkynes (**Figure 15**, Ec. 2) [53] and in the synthesis of spiroacetals among others [54].

In these approximations the degree of enantio-discrimination depends upon the proximity of the counteranion to the cationic gold center. In this sense, recently have been designed new phosphine ligands, thetered to chiral phosphoric acids, with the aim to restring the flexibility of the ion pair. The new phosphoric acidtethered phosphines have shown excellent levels of enantioselectivity in reactions proceeding through carbocationic intermediates, such us the cyclization-addition of heteronucleophiles to enones (**Figure 16**) [55].
