3.6 Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

3.6 Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid Y Ukaji and T Soeta, Kanazawa University, Kanazawa, Japan r 2012 Elsevier Ltd. All rights reserved.

3.6.1 3.6.2 3.6.3 3.6.3.1 3.6.3.2 3.6.3.3 3.6.4 3.6.5 3.6.6 References

3.6.1

Introduction Use of Tartaric Acid and its Acid Derivatives for Asymmetric Reactions Tartaric Acid Esters Tartaric Acid Esters–Metal Complexes for Asymmetric Allylation and Propargylation Katsuki–Sharpless Epoxidation Tartaric Acid Esters for Other Various Types of Asymmetric Reactions Asymmetric Reactions Promoted by Tartramide–Metal Complexes Miscellaneous Conclusion

176 176 183 183 184 189 194 198 200 200

Introduction

Tartaric acid (2,3-dihydroxybutanedioic acid) is a naturally occurring dicarboxylic acid containing two stereocenters. It exists as a pair of enantiomers and an achiral meso compound. The dextrorotatory enantiomer of (R,R)-L-(þ)-tartaric acid is widely distributed in nature. It is present in many fruits (fruit acid), and its monopotassium salt is found as a deposit during the fermentation of grape juice. Pure levorotatory (S,S)-D-()-tartaric acid is rare. Tartaric acid is a historical compound, dating back to when Louis Pasteur separated it into two enantiomers with a magnifying lens and a pair of tweezers more than 160 years ago. It is manufactured from potassium hydrogen tartrate (wine tartar, cream of tartar – a by-product of the wine-making industry) via the calcium salt. (S,S)-Tartaric acid is also available commercially; it can be obtained from the racemic acid by several resolution procedures or from D-xylose. The highly functionalized and C2-symmetric tartaric acid molecule is perfectly tailored for applications as a resolving agent and chiral ligand. In fact, tartaric acid is the most frequently used resolving agent for racemic amines.1

3.6.2

Use of Tartaric Acid and its Acid Derivatives for Asymmetric Reactions

Tartaric acid has two salient features: (1) that the oxygen could coordinate to metals and (2) that two types of hydrogen might participate in hydrogen bonding (Figure 1). Its pKa1 is 3.0 (H2O) and pKa2 is 4.3 (H2O). Its metal salts are readily available. For example, the zinc salt is prepared from (R,R)-tartaric acid and zinc acetate or potassium-sodium (R,R)-tartrate (Rochelle salt) and ZnCl2. The zinc tartrate salt catalyzed ring opening of cyclohexene oxide by BunSH to give the corresponding thio-cyclohexanol with up to 85% ee as reported by Yamashita (equation 1).2 coordination sites for metal ions

O H

O

proton source

H O

O H

O

H

O

Figure 1 Tartaric acid as a chiral auxiliary. Reproduced from Figure 2.1 in Gawron´ski, J.; Gawron´ska, K. Tartaric and Malic Acids in Synthesis; Wiley: New York, 1999, Chapter 1–8, with permission from Wiley.

O

+

BunSH

ZnT (0.1 equivalent)

OH SBun

ZnT = zinc(II) (R,R)-tartrate

176

ð1Þ

82%, 85% ee

Comprehensive Chirality, Volume 3

http://dx.doi.org/10.1016/B978-0-08-095167-6.00306-2

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

177

Tai, Harada, and Izumi introduced tartaric acid as a chiral additive to Raney nickel catalysts (RNi) for hydrogenation of prochiral ketones.3,4 This reaction is sensitive to conditions and catalyst preparation. The absorbed tartaric acid on the Ni surface was considered to provide the enantiodifferentiating site only when it existed as a mono sodium or disodium salt. The Raney nickel catalyst modified by tartaric acid, NaOH, and NaBr (TA-NaBr-MRNi) was found to be the most useful catalyst. A nonenantio-differentiating site might be removed chemically, at least in part, by acid corrosion and deactivated by partial poisoning with absorbed NaBr. Furthermore, a catalyst subjected to ultrasonic irradiation (TA-NaBr-MRNi-U) showed a high reactivity and selectivity toward methyl 3-oxoalkanoates affording up to 98% ee (equation 2).5

O R

O

OH

H2/(R,R )-TA-NaBr-MRNi-U R

O

O O

ð2Þ

R = Prc >98% ee 86% ee CH3 CH3CH2 92% ee CH3(CH2)10 94% ee

Tartaric acid has been shown to be a promising candidate for the chiral auxiliary for NaBH4-reduction. Yatagai and coworkers reported that the NaBH4/tartaric acid complex was able to selectively reduce a-ketoesters and b-ketoesters with good enantioselectivity (equation 3).6

O HO

COOH

NaBH4 HO

COOH

O

Ph

OEt

THF, reflux

HO

O

Ph

OEt

ð3Þ 87%, 86% ee

Nozaki and coworkers developed a series of chiral bimetallic Lewis acids, prepared from (R,R)-tartaric acid and arylboronic acids. First, they found that these Lewis acids selectively bound both achiral and chiral diamines.7 They also reported an enantioselective reduction of unsymmetric ketones by LiBH4 in the presence of a stoichiometric amount of the chiral bimetallic Lewis acid with moderate to good enantioselectivity up to 99% ee as shown in equation 4.8 CF3 O O B O

F3C

O (1.0 equivalent)

O CF3 NH2

O B O

CF3

LiBH4 (1.0 equivalent)

OH

ð4Þ

*

NH2 (+) 99% ee

Singaram and coworkers developed an alternative chiral Lewis acid by the condensation of phenylboronic acid with tartaric acid: An equimolar mixture of phenylboronic acid and tartaric acid was refluxed in THF over two equivalents of CaH2 to produce the active reagent, which they termed ‘TarB-X’ (equation 5). 1H NMR analysis of TarB-X supported the formation of a boroxane ring and maintenance of the C2-symmetry of the tartaric acid moiety. Additional proof of the existence of free carboxylic acids was obtained from IR measurements and the generation of two equivalents of H2 gas on the treatment of m-nitro-TarB (TarB-NO2) with LiBH4. The free carboxylic acids were found to be necessary to achieve high enantioselectivities owing to the formation of acyloxyborohydrides.9–13

178

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

X

HO

OH

CO2H

CaH2

B OH

HO

X

THF reflux

CO2H

O

CO2H

O

CO2H

B

ð5Þ

TarB-X

This new asymmetric reducing system using TarB-NO2 and LiBH4 was very effective for aromatic ketones, giving the corresponding alcohols in high enantiomeric purity. However, the highly reactive nature of lithium borohydride made it somewhat difficult to handle. A less reactive hydride source, such as sodium borohydride, was investigated as an ideal replacement due to its stability to air and moisture. Additionally, lithium borohydride is 16 times expensive than sodium borohydride and must be handled with care because it is pyrophoric. Finally, they established an optimized reaction procedure involving addition of two equivalents of NaBH4 in a single portion to a solution of ketone/TarB-NO2 (1:2) in THF at 25 1C. Addition of the NaBH4 caused a rapid evolution of H2 gas which subsided after approximately 15 min. The reaction was complete in less than 30 min and the product alcohol was obtained in very high enantiomeric excess and with 100% conversion. Not only aromatic but also aliphatic substrates were reduced by NaBH4 in the presence of (R,R)-TarB-NO2. For example, a variety of a,b-unsaturated alkenyl and alkynyl ketones were reduced with excellent enantioselectivity although a stoichiometric amount of TarB-NO2 was necessary (equation 6). (R,R)-TarB-NO2 NaBH4

O RL

RS

OH RS

RL

OH

OH

OH

Br

ð6Þ 99% ee

99% ee

OH

OH

99% ee OH Bun

96% ee

99% ee

90% ee

The authors proposed that a single monoacyloxyborohydride moiety per TarB-NO2 molecule was active species, which was supported by 11B NMR and the measurement of H2 gas evolution of at the NaBH4 titration. They speculated that the carbonyl oxygen of the prochiral ketone substrate coordinated to the boron of the TarB-X reagent, thus preferentially presenting one face of the ketone for attack by an acyloxyborohydride moiety. The reductions of a,b-ynones showed a reversal enantioselection, which is explained by an alternative model shown in Figure 2, which is based on ab initio calculations and experiment including spectroscopic studies.13

RL

H H B H O O

O RS O B O

Na OH

H

RL

H CO2H

RS

O2N RL RS

H H B H O O

O B O2N

O O

H

OH

Na RL

RS

H CO2H

Figure 2 Proposed transition states for the reduction with TarB-NO2. Reproduced from Figure 11 and 12 in Eagon, S.; DeLieto, C.; McDonald, W. J.; et al. J. Org. Chem. 2010, 75, 7717–7725, with permission from American Chemical Society.

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

179

As described later, Yamamoto and coworkers reported the asymmetric Diels–Alder reaction of naphthoquinone derivatives in the presence of a chiral boron reagent derived from B(OMe)3 and (R,R)-tartaric acid diamide.14 Both the rate enhancement and the high enantioselectivity observed for this type of auxiliary could be ascribed to the novel intramolecular hydrogen bonding between the hydrogen atom of the amide and the oxygen atom attached to the boron center.15 In followup studies, they reported a chiral acyloxyboron (CAB) catalyst derived from a tartaric acid. The CAB catalyst 2 was prepared from monoacylated tartaric acid 1 and 1 equivalent of BH3  THF (equation 7). This was the first example of a Brønsted acid-assisted Lewis acid catalyst (BLA), which is one of the four types of ‘combined acids.’ The high reactivity of the tartaric acid derived catalyst originated from intramolecular hydrogen bonding of the terminal carboxylic acid to the alkoxy oxygen (Figure 3).15,16 O RO

CO2H

O

CO2H

O

OH

RO

O

+ BH3·THF

1

RO

CO2H O

RO

O O BH

CAB 2

ð7Þ

a; R = Me b; R = Pri

M + O H

O

Figure 3 Brønsted acid assisted Lewis acid catalyst (BLA). Reproduced from Figure 5 in Yamamoto, H. Tetrahedron 2007, 63, 8377–8412.

Yamamoto also described the first CAB catalyzed Diels–Alder reactions of simple achiral a,b-unsaturated carboxylic acids and a,b-unsaturated aldehydes to bring about remarkable asymmetric induction in a truly catalytic manner (equation 8). The practicability of this new method is one of its most attractive aspects as exemplified by (1) the chirality sources (tartaric acids) are easily obtainable in both enantiomeric forms at low cost, and thus either enantiomer of the desired Diels–Alder adduct can be synthesized with high enantiomeric excess; (2) simple a,b-unsaturated aldehydes could be used without any derivatization, making further transformation of the adducts easy; (3) only a catalytic amount (10 mol% or less) of chiral Lewis acid was needed; and (4) the reaction was operationally simple to perform, and the workup and isolation procedures were also uncomplicated so that excellent reproducibility was possible.17–20

R

+

CAB 2 (10 mol%) R1

R

CHO

CHO R1

ð8Þ CHO

CHO

CHO

61%, 97% ee

85%, 96% ee

Br 94%, 95% ee

CAB 2a

CAB 2a

CAB 2b

Based on a series of NOE experiments, it was established that the effective shielding of the CAB-coordinated aldehydes arose from p stacking of 2,6-diisopropoxyphenyl ring and the coordinated aldehyde (Figure 4).21 Hydrogen bonding makes boron more acidic! O O O

H H O O H

PriO

O O B H O OPri

up to 94−96% ee of Diels−Alder, aldol and ene reaction

Figure 4 CAB–methacrolein complex. Reproduced from Figure 4 in Yamamoto, H. Tetrahedron 2007, 63, 8377–8412.

180

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

Chiral acyloxyborane complex 2a also promoted an intramolecular Diels–Alder reaction of 2-methyl-(E,E)-2,7,9-decatrienal with high diastereo- and enantioselectivity (92% ee) as shown in equation 9.22

CHO

CHO

CAB 2a (10 mol%)

ð9Þ 84%, 92% ee

Alternative stable CAB complexes 3 were easily prepared from O-acyl tartaric acid 1b and aryl or alkylboronic acid, avoiding use of BH3  THF (equation 10). In contrast to CAB 2 prepared using BH3  THF, which was both air and moisture sensitive, the B-alkylated catalysts 3 were stable and could be stored in closed containers at r.t. The catalyst, which exists as a monomeric species as suggested by cryoscopic molecular weight determination, was effective in catalyzing the hetero Diels–Alder reaction. For example, the hetero Diels–Alder reaction of aldehydes with Danishefsky diene was promoted by 20 mol% of this catalyst solution. After the usual workup, the crude adduct was treated with trifluoroacetic acid to afford dihydropyrone (equation 11).23

O PriO

CO2H O

O

CO2H OH

PriO

PriO

O

+ RB(OH)2 PriO

1b

CAB 3

MeO a; R = Ph

b; R =

CO2H O O O B R

ð10Þ

CF3 c; R =

PhO d; R =

CF3

OMe + Me3SiO

(i) CAB 3b (20 mol%)

O R1

H

(ii) CF3CO2H

O O

R1

ð11Þ R1 = Ph 4-MeC6H4 (E)-PhCH=CH (E)-MeCH=CH

95%, 97% ee (2R, 3R) >99%, 97% ee 86%, 97% ee (2S, 3R) 79%, 92% ee

The same authors also applied CAB chemistry to catalytic asymmetric Mukaiyama aldol condensations. In the presence of 20 mol% of the CAB 2b, prepared from BH3  THF, achiral silyl enol ethers or ketene silyl acetals reacted with achiral aldehydes to afford the corresponding aldol-type adducts in good yields with high enantio- and diastereoselectivities (equation 12). Furthermore, the reactivity in aldol-type reactions could be improved without reducing the enantioselectivity by the use of 10–20 mol% of the CAB complex 3c prepared from 3,5-bis(trifluoromethyl)phenylboronic acid. The enantioselectivity was also improved without reducing the chemical yield by the use of 20 mol% of the CAB complex 3d prepared from o-phenoxyphenylboronic acid. Regardless of the stereochemistry (E or Z) of starting enol silyl ethers generated from ethyl ketones, syn-aldols were highly selectively obtained in these reactions. The observed syn-selectivities and reface attack of nucleophiles on carbonyl carbon of aldehydes implied that an extended open transition-state model was applicable.24

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

OSiMe3 RCHO

+

R2

HO

(i) CAB 2 or 3

R1

O R1

R

(ii) HCl

181

R2 HO

O

Ph

HO

O

HO Ph

Ph

Ph

Ph

Bu

HO

O

O

Ph

ð12Þ

from (Z)-enol CAB 2b (20 mol%) 81%, 85% ee CAB 3c (10 mol%) 96%, 83% ee CAB 3d (20 mol%) 91%, 88% ee

CAB 2b (20 mol%) 98%, 85% ee CAB 3c (10 mol%) 99%, 88% ee CAB 3d (20 mol%) 93%, 91% ee

CAB 2b (20 mol%) 86% (syn/anti = 95/5) 95% ee CAB 3c (10 mol%) 92% (syn/anti = 99/1) 96% ee

CAB 2b (20 mol%) 57% (syn/anti = >95/5) >95% ee CAB 3c (10 mol%) 83% (syn/anti = >95/5) 97% ee

The first catalytic enantioselective Sakurai–Hosomi allylation was also developed using CAB as a catalyst. In the presence of 10–20 mol% of CAB complex 2b, allylation of both aromatic and aliphatic aldehydes proceeded smoothly. Unfortunately, simple allyltrimethylsilane was not sufficiently reactive under the reaction conditions employed. In this allylation, the reactivity could again be improved without reducing the enantioselectivity by using the CAB complex 3c (equation 13). The observed selectivities and re-face attack of nucleophiles on the carbonyl carbons of aldehydes implied that the present allylation also proceeded via an extended open transition state.25 (i) CAB 2b or 3c (20 mol%)

R1 RCHO

+

R2

SiMe3

HO

HO

R1

HO R

(ii) Bu4NF

R2 HO

HO

ð13Þ

Ph

Ph

Ph

Bu

CAB 2b 46%, 55% ee

CAB 3c 94%, 91% ee

CAB 3c 77% (94/6) 91% ee

CAB 3c 70%, 63% ee

Sugiura and coworkers found that o-mono-3,5-di(tert-butyl)benzoyl tartaric acid (4) catalyzed asymmetric conjugate addition of boronic acids to enones with good enantioselectivity (equation 14). The addition of methanol (two equivalents relative to the boronic acid) at a higher concentration improved both the yield and selectivity. Methanol was suggested to suppress the noncatalyzed reaction. (E)-Styrylboronic acid afforded the adducts with up to 87% ee. A specific reaction mechanism was not proposed, however, the possibility that an O-benzoyl tartaric acid-boron complex was the actual catalyst could not be ruled out based on 1H NMR analysis.26 O But

O

CO2H CO2H

OH 4 (0.1 equivalent)

But MeOH (2.0 equivalent)

O R1

R2

+

(HO)2B−R3

O R1

R3 R2

ð14Þ

Ph O O Ph

Anp 84%, 87% ee

O Ph Ph 79%, 81% ee

Schaus and coworkers developed a dual catalyst system for the enantioselective addition of boronates 5 to chromene acetals. The catalyst system was comprised of catalytic amounts of a tartaric acid derived Brønsted acid 6 used in conjunction with a catalytic amount of a lanthanide triflate Lewis acid. This combination catalyzed the enantioselective addition of alkenyl and aryl boronates to chromene acetals (equation 15).27

182

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid O

OH

HO

R1

EtO B EtO

+ O

OEt

R3

Bn N

Bn OH O 6 (5 mol%) Ce(OTf)4 (4.5 mol%) R1 R3

O

R2

R2

5 (1.5 equivalent)

MeO

Ph

O 74%, 92% ee

Hexn

O

Anp

O

75%, 98% ee

ð15Þ

60%, 97% ee

Studies were performed to ascertain the roles of the catalysts and determine the species formed during the course of the reaction (Scheme 1). In the first step, the addition of boronate 5 to diol 6 results in an exchange process to form the dioxaborolane 7, which was established by analysis of the 1H NMR, FT-IR, and ESI-MS spectra of the mixture. The interaction of Ce(OTf)4 with 7 was supported by ESI-MS and FT-IR analyses. Ce(OTf)4 was thought likely to bind to an oxygen of the boronate. They proposed a possible catalytic cycle as shown in Scheme 1. The catalytic cycle might begin with the formation of dioxaborolane 7 from the boronate 5 and tartramide acid 6. The addition of cerium Lewis acid to complex 7 enhanced the acidity of the boronate. After the association with chromene acetal, the boronate facilitated pyrylium formation concomitant with generation of boronate 8. Activation through formation of the ‘ate’ complex 8 led to the nucleophilic addition of the styryl group to the electrophile to provide the formation of product and the necessary reservoir of tartramide acid for reentry into the catalytic cycle. O

HO O O

Ph Bn N

+B(OEt)3

Bn

HO O

O O O M O B H O

O +

O

Ph 5

O O O B

Bn N

8 Et

EtO B EtO

OH Bn 6

2 EtOH

Bn N

Ph

OH

Bn

Ph 7

M = Ce(OTf)4 or Yb(OTf)3 +M O

OEt

Scheme 1 Proposed catalytic cycle. Reproduced from Scheme 2 in Moquist, P. N.; Kodama, T.; Schaus, S. E. Angew. Chem. Int. Ed. 2010, 49, 7096–7100, with permission from Wiley.

Terada and coworkers reported an enantioselective aza-Friedel–Crafts reaction of indoles with an a-imino esters catalyzed by O,O0 -diacyl tartaric acid. The reaction of indole with the a-imino ester proceeded smoothly in the presence of 10 mol% O,O0 -di-ptoluoyl-(S,S)-tartaric acid (9) monohydrate in toluene at  60 1C and the corresponding optically active Friedel–Crafts product was obtained. When the amount of water was increased to 10:1 (water/9), enantioselectivity was further improved to 73% ee. Finally, employing 30 mol% of the catalyst including 10 equivalents of water 9 10H2O at  80 1C resulted in an increase in the enantioselectivity up to 88% ee (equation 16).28 HOOC O O

COOH O O

MeO

MeO + X

N OEt

H O

9· nH2O (catalyst)

ð16Þ

NH

X

N H

OEt

* N H

O

X = H, 90% 88% ee

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

183

Kita and coworkers reported a catalytic asymmetric oxidation of sulfides in water using the hypervalent iodine(V) reagent PhIO2, MgBr2, and O,O0 -dibenzoyl-(S,S)-tartaric acid (10) to give sulfoxides with enantioselectivities up to 63% ee (equation 17).29 HOOC O O

COOH O O

10 (10 mol%)

Ar

S

ð17Þ

PhIO2 (55 mol%) MgBr2 (20 mol%)

Me

O S Ar Me Ar = Ph; quantitative 60% ee Tolm; quantitative 63% ee

3.6.3 3.6.3.1

Tartaric Acid Esters Tartaric Acid Esters–Metal Complexes for Asymmetric Allylation and Propargylation

Yamamoto and coworkers developed an asymmetric propargylation reaction using chiral allenyl boronic esters derived from tartaric acid esters. Based on the anti-coplanar arrangement of carbonyl–boron–allene moieties in the reactive complex, they postulated the clockwise rotation of the C–O bond before C–C bond formation (Scheme 2). The reaction scheme demonstrated that the symmetry element coordinated to the metal center did have a significant effect on the direction of the C–O rotation and thus on the asymmetric induction of the reaction. Aromatic and a,b-unsaturated aldehydes gave lower enantioselectivities. Generally, diisopropyl tartrate (DIPT) gave a slightly higher enantiomeric excess than diethyl tartrate (DET) affording the chiral propargylic alcohols with enantioselectivities up to 95% ee.16,30 COOR1

O H2C C C B H O

(R,R)-tartrate H2C C C B(OH)2 H

COOR1

clockwise rotation of C−O bond

R1

H

C

C

H

COOR1 O O

H H

= Et or Pri

steric

R C

RCHO

B

O

C

R

H H

C

O

+

–

B

COOR1

H H

C

C

C

O O

COOR1 H H COOR1

OH R up to > 95% ee

H

H

Scheme 2 Rotation of C–O bond after coordination of Lewis acid reagent. Reproduced from Figure 2 in Yamamoto, H. Tetrahedron 2007, 63, 8377–8412.

Roush introduced the tartrate allylboronates 11 and applied them to allylation of aldehydes. The stereoselectivity of these reactions was sensitive to reaction temperature, solvent (toluene was best for aliphatic aldehydes; THF was preferred for aromatic aldehydes), and moisture. The use of molecular sieves was recommended to maintain an anhydrous reaction medium. The corresponding homoallylic alcohols were obtained with up to 87% ee (typically 60–87% ee) (equation 18). They proposed that transition-state A was favored as a consequence of ‘lone pair–lone pair’ repulsion involving the aldehydic oxygen atom and the front side ester group in Figure 5 that destabilizes transition-state B relative to A.31,32

CO2Pri O B O

O R

H

MS 4 Å

CO2Pri 11

NaBH4

OH R up to 87% ee

ð18Þ

184

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

These authors next developed allylboronate 12 containing a conformationally rigid tartramide auxiliary. The new chiral auxiliary appeared to meet the criterion of synthetic utility realizing enantioselectivities of up to 97% ee (equation 19). As long as the tartrate unit was constrained within an eight-membered ring, the critical conformational features were enforced and intermediate aldehyde complexes with 12 existed only in conformations analogous to A in Figure 5 (Figure 6).33,34 R1

O N B

OH

12

RCHO

MS 4 Å

R

N

R = Ph; 12a 40%, 97% ee R = Hexc; 12a 75%, 85% ee R = C5H11; 12b 93%, 97% ee

O

CO2Pri O B O

H H HR

a; R1 = Ph b; R1 = Hexc

O O

ð19Þ

R1

12

PriO2C O O B

PriO

CO2Pri

O

O

H H O

RH

B (disfavored)

A (favored)

Figure 5 Disfavored ‘lone pair–lone pair ’ repulsion. Reproduced from Roush, W. R.; Banfi, L. J. Am. Chem. Soc. 1988, 110, 3979–3982, with permission from American Chemical Society.

R

R1 O

N

+

H O B O

H H H

R

N

O

R1

B

clockwise B-O rotation avoids repulsive n/n interaction

O

O –

N

R1

O O N

R1

O

Figure 6 Plausible transition state for the allylboration with tartramide. Reproduced from Roush, W. R.; Banfi, L. J. Am. Chem. Soc. 1988, 110, 3979–3982, with permission from American Chemical Society.

Mukaiyama and coworkers also reported that a chiral allylating reagent, generated in situ from Sn(II)(O2C6H4), allyl bromide, tartrate, and DBU, smoothly reacted with aromatic aldehydes in the presence of a catalytic amount of CuI to afford the corresponding homoallylic alcohols with up to 94% ee (equation 20).35

O

O SnII O O

COOBut COOBut

2(DBUH+)

3.6.3.2

2–

Br catalyst CuI

O

O

COOBut

O

COOBut

Sn O

(DBUH+)

–

ArCHO

OH

ð20Þ Ar up to 94% ee

Katsuki–Sharpless Epoxidation

One of the most successful applications of tartaric acid derivatives for asymmetric reactions is Katsuki–Sharpless epoxidation.36,37 Success was achieved by the use of a titanium–tartrate complex as the catalyst based on the following considerations and serendipitous discoveries: (1) A metal alkoxide having more than two alkoxy ligands could be a catalyst for the asymmetric epoxidation of allylic alcohol, in particular, the use of metal tetraalkoxides such as Ti(OR)4 was found to be advantageous because an optically active diol could form stable chelate complexes with it, and such stable chelate formation was expected to suppress the in situ formation of undesired metal species which might catalyze poorly or nonenantioselective epoxidation processes. (2)

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

185

The titanium complex bearing a multidentate ligand was found to show higher catalytic activity than the parent titanium tetraalkoxide, an example of so-called ligand acceleration. Interestingly, ligand acceleration was not observed in the epoxidations using hafnium, vanadium, niobium, or tantalum complexes as a catalyst. Epoxidation of primary allylic alcohols using Ti(OPri)4, DET (or DIPT), and ButOOH system generally proceeded with high enantioselectivity, greater than 90% ee, and enantiofacial selectivity was determined by the chirality of the tartrate used. A mnemonic was developed whereby an allylic alcohol, when drawn as shown in Figure 7, allows oxygen atom transfer from the bottom face of the olefin in the reactions using (R,R)-DET (or DIPT) and from the top face in reactions using (S,S)-tartrate. Titanium-catalyzed epoxidation could be performed in a catalytic manner like other metal-catalyzed epoxidations, but the first reported titanium–tartrate mediated epoxidation was a stoichiometric reaction because the titanium–tartrate complex was highly sensitive to water. Thus, catalytic version was first realized when the reaction was performed in the presence of MS 3 A˚ or 4 A˚.38 Catalytic asymmetric epoxidation has the following advantages over the stoichiometric reaction: (1) The workup procedure is easier, especially when the resulting epoxy alcohols are highly water soluble; (2) higher substrate concentrations are possible; (3) products can be derivatized in situ as needed; (4) many Lewis acid-sensitive epoxy alcohols tolerate the catalytic conditions; and (5) the catalytic reaction is more economical. In spite of these advantages, the stoichiometric reaction is still used in many organic syntheses probably because all the reagents required for the reaction are cheap and stoichiometric reactions show 1–5% better enantioselectivity than catalytic reactions in most cases. It should be noted that the use of 10–20% excess of tartrate to titanium alkoxide is recommended for this epoxidation to realize success by employing either the catalytic or stoichiometric conditions. Regardless of substitution pattern of the olefinic substrate, high enantioselectivities, usually 490% ee have generally been realized. DIPT, DET, and dimethyl tartrate (DMT) have been used equally as a chiral source for the unhindered allylic alcohols. One limitation encountered is substitution of a bulky group in Z-position (R3). For these substrates, enantioselectivity was significantly decreased (equation 21).36d

(S,S)-dialkyl tartrate O R1

Ti(OPri)4 ButOOH

R3

R2

R1 O

R3

R2

OH

OH R1

R3 O

R2

OH

O (R,R)-dialkyl tartrate Figure 7 Mnemonic for Katsuki–Sharpless epoxidation. Reproduced from Scheme 4 in Katsuki, T. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999, Chapter 18.1, with permission from Springer.

R1

OH

R2

O

Ti(OPri)4, catalyst (R,R)-DET(or DIPT) R1 ButOOH (or PhMe2CCOOH)

R3

R2

O

OH

O

OH

95% ee

90−92% ee

R3 O

OH

95% ee

O

OH

92% ee

O

OH

OH

94% ee

O

OH

>88% ee

ð21Þ

(stoichiometric) But O But

OH

85% ee (stoichiometric)

O

OH

95% ee (stoichiometric)

But O OH 25% ee (stoichiometric)

An alkenyldimethylsilanol, which is structurally similar to an allylic alcohol, could also function as a substrate for asymmetric epoxidation to give the corresponding epoxy silane. Protodesilylation by fluoride ion provided a terminal epoxide with 90% ee (equation 22).39

186

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

Ti(OPri)4, (R,R)-DIPT ButOOH

Octn Si

Octn

OH

Octn

Et4NF

O Si

O

O

ð22Þ

2

60%

90%, 90% ee

The titanium–tartrate complex has been proven to have a dimeric structure by X-ray analysis. The complex has been believed to maintain its dimeric structure in solution (Figure 8). Based on the X-ray structure, Sharpless proposed the transition-state model 13 for such titanium–tartrate catalyzed epoxidations (Scheme 3). Coordination of the distal oxygen (O2) to Ti atom activates the peroxy bond and hence facilitated the intramolecular nucleophilic attack of the double bond on the electrophilic oxygen (O1). In fact, the nucleophilicity of the olefin was shown to depend on the electron density of the olefinic bond. For example, epoxidation of p-methoxycinnamyl alcohol was found to be 10 times faster than that of p-nitrocinnnamyl alcohol.36a In addition, the epoxidation of an allylic alcohol bearing an electron withdrawing cyano group required a long reaction, although standard enantioselectivity was observed (equation 23).40 Furthermore, the transition-state model 13 could also reasonably explain the relative enantioselectivity observed for various substrates in this reaction: The coordinated substrate preferentially assumed a conformation having a small dihedral angle (O–C–CQC, c. 301) to deliver the olefinic moiety at the appropriate position in space for the epoxidation. When R3, which is directed toward the ligand, is a bulky substituent, it becomes difficult for the substrate to assume the required conformation, decreasing enantioselectivity to a considerable extent.36,41,42 R5 OR RO

Ti

O

R2 O Ti R3 E O1 R1 2 O

O RO

R4

O

E O E O

But

Figure 8 Dimeric model of titanium–tartrate complex. Reproduced from Figure 1 in Katsuki, T. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999, Chapter 18.1, with permission from Springer.

R5 RO2C R3

O

R4 1 R2

O R1

O

O

HO

O2

R2 O R3

R1 R1

O

R2

R3

OH (R4 = R5 = H)

CO2R

But 13

Scheme 3 Proposed transition state model for Katsuki–Sharpless epoxidation. Reproduced from Figure 1 in Katsuki, T. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999, Chapter 18.1, with permission from Springer.

NC

OH

Ti(OPri)4, catalyst (R,R)-DIPT ButOOH, MS 4 Å 10 days

NC

O

OH

ð23Þ

81%, 91% ee

In the epoxidation of racemic secondary alcohols, two stereochemical problems must be considered: (1) differentiation of the enantiomers (kinetic resolution) and (2) diastereofacial selection in the epoxidation. When a racemic allylic alcohol was subjected to epoxidation using (R,R)-tartrate, the (S)-enantiomer of the alcohol reacted faster than the (R)-enantiomer to afford the antiepoxy alcohol with high stereoselectivity (Scheme 4). By analogy to primary allylic alcohols, a secondary allylic alcohol bearing a bulky E-substituent (R1) was a good substrate for kinetic resolution. Best substrates were those in which the E-substituent was trimethylsilyl, iodo, or trimethylstannyl. The relative rate constant for (E)-1-trimethylsilyl-l-octen-3-ol was 700, and at 50% conversion, both the unreacted alcohol and the anti-epoxy alcohol had more than 99% ee (equation 24).43 The efficiency of the kinetic resolution could be easily explained based on transition model 13. The coordinated substrate suffered from steric hindrance when R4aH, and epoxidation of such a substrate should be strongly retarded resulting in the observed kinetic

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

187

resolution of racemic secondary allylic alcohols (Scheme 4). Specifically, the enantiomer (R4aH, R5 ¼ H) reacted much slower than antipode (R4 ¼ H, R5aH). The poor reactivity of tertiary allylic alcohols could also be explained based on this reasoning. R1

Ti(OPri)4 ButOOH

R3

R2 5 R

OH

R1 R2

fast

(S)

R1

R3 O OH

R2 H

OH R4

R5 H

H

R3

Ti(OPri)4 ButOOH

R1 R2

slow

(R)

R3 O OH

H R4

anti

syn O

O

(R,R)-dialkyl tartrate

(R,R)-dialkyl tartrate

Scheme 4 Kinetic resolution of racemic allylic alcohols by Katsuki–Sharpless epoxidation. Reproduced from Scheme 4 Katsuki, T. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999, Chapter 18.1, with permission from Springer.

Me3Si

Ti(OPri)4, (R,R)-DIPT ButOOH (0.6 equivalent)

C5H11n

Me3Si

O

C5H11n

(krel = 700)

OH

C5H11n

Me3Si

OH

stoichiometric catalytic

OH 42%, >99% ee 44%, 94.9% ee

42%, >99% ee 42%, >99% ee

ð24Þ

But OH (krel = 104)

OH (krel = 300)

Heterocyclic compounds such as furan, thiophene, and pyrrole were substrates for epoxidation. Similar to secondary allylic alcohols, 2-(l-hydroxyalkyl) derivatives of these heterocyclic compounds were also good substrates for kinetic resolution. The oxidation of 2-furyl alcohols 14 using (R,R)-DIPT provides (R)-furyl alcohols (R)-14 (495% ee) and a pyranone 15 when 0.6 equivalent of TBHP were used (equation 25).44a A chemoselective oxidative kinetic resolution has also been realized: Oxidation of racemic (E)-1-(2-furyl)-2-buten-1-ol (16) using (R,R)-DIPT as a chiral source provided an (R)-epoxy alcohol 17 (497% ee) and an (S)-pyranone 18 (497% ee), both in 41% yields (equation 26).44b

X

R

O

Ti(OPri)4, (R,R)-DIPT ButOOH (0.6 equivalent)

(S) R

X

O OH

Ti(OPri)4, (R,R)-DIPT ButOOH

O O

(S) (R)

O

O OH 16

ð25Þ

OH (R)-14 >95% ee

XH 15

14 X = O, NH

(R ) R

O

ð26Þ

OH (R)-17 41%, >97% ee

(S)-18

OH

41%, >97% ee

Schreiber and coworkers reported that oxidation of prochiral dialkenyl carbinols 19 provided the anti-(S)-epoxide 20 possessing extremely high optical purity.45 The first epoxidation occurred in an enantiotopically selective manner whereas the second one proceeded in an enantiodifferentiating manner (kinetic resolution). In the second step, the minor (R)-monoepoxides (R)-20 were consumed faster than the major (S)-enantiomers (S)-20 and therefore the enantiomeric excess of the major anti-(S)-monoepoxide 20 increased as the reaction proceeded (Scheme 5). Actually, in the epoxidation of 1,4-pentadien-3-o1 using (R,R)-DIPT, the enantiomeric excess of the major anti-21 was observed to increase from 84% ee ,93% ee, up to 497% ee as the reaction time was extended.45 Lin and coworkers reported that catalytic asymmetric epoxidation of 1,4-pentadien-3-o1 also afforded the expected products with excellent enantio- and diastereoselectivity (97% ee and 98% de) (anti:syn¼ 99:1) in 65% yield (equation 27).46

188

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

R

R

(S)

R

O

R

OH anti-(S)-20

fast R

O

R

OH 19

O

(S)

OH R

O

R

OH syn-(S)-20 R

O

R

R

R

OH

(R)

R

R

OH O

R

OH (R)-20

O

O

fast R

OH

Scheme 5 Epoxidation of meso-secondary diallylic alcohols. Reproduced from Katsuki, T. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999, Chapter 18.1, with permission from Springer.

Ti(OPri)4, (R,R)-DIPT ButOOH

O

OH

OH 21

ð27Þ

stoichiometric reaction: 84% ee, 92% de, 3 h 93% ee, 99.7% de, 24 h >97% ee, >99.7% de, 140 h catalytic reaction: 97% ee, 98% de, 10 days

As described above (Section 3.6.3.2) Katsuki–Sharpless epoxidation is now one of the most common asymmetric reactions to prepare the oxygen containing compounds. The features of this reaction are (1) relative insensitivity to resident substrate chirality (reagent control), (2) high reliability and predictability of absolute configuration, (3) high enantiomeric purity of the epoxide – generally greater than 90%, (4) commercially available and inexpensive reagents, and (5) catalytic in the titanium–tartrate complex (usually 0.05–0.15 equivalent) when used in conjunction with MS 4 A˚. Sharpless and coworkers also applied the asymmetric epoxidation to homoallylic alcohols. The reaction was considerably slower as compared with reaction of allylic alcohols to give the corresponding epoxides with opposite enantiofacial selection and moderate levels of enantioselectivities.47 Katsuki and coworkers found that c. 1:1 combination of Zr(OPrn)4, dicyclohexyltartramide achieved good enantiomeric selectivities (up to 77% ee) especially for (Z)-homoallylic substrates (equation 28). They postulated that there was an appreciable repulsion between a hydrogen atom at C-1 and the substituent R in the transition state of (Z)-homoallylic alcohol (Figure 9). It was also speculated that reducing the repulsions in the folded conformation by the stretching the folded carbon chain could enhance the asymmetric induction. Such reduction in repulsion could result when a Zr catalyst, which has longer metal–oxygen bonds than titanium, was employed.48

OH

O

ButOOH

OH

R

R R = Et (Z), Ti(OPri)4, (R,R)-DIPT R = Et (Z), Zr(OPrn)4, (R,R)-DCTA R = Me (Z), R = Et (E),

RO2C

O 30%, 50% ee 23%, 72% ee 25%, 77% ee 38%, 43% ee

O

O1

HO

NHHexc NHHexc

ð28Þ

O DCTA

H H R

O

HO

O

O2 But

CO2R

Figure 9 CPK model examination for epoxidation of homoallylic alcohols. Reproduced from Figure 1 in Ikegami, S.; Katsuki, T.; Yamaguchi, M. Chem. Lett. 1987, 16, 83–84, with permission from Chemical Society of Japan.

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

189

Onaka and coworkers developed a catalytic enantioselective epoxidation of homoallylic alcohols using Zr(OBut)4 and tartrate. They revealed two significant findings: (1) a catalytic epoxidation using Zr(OBut)4 and DIPT or DBTA (N,N’-dibenzyl tartramide) in a 1:1 ratio afforded the corresponding (3S)-epoxides, and (2) on the contrary, a catalytic system from a 1:2 mixture of Zr(OBut)4 and DIPT produced the opposite enantiomer with a (3R)-configuration whereas Zr(OBut)4 and DBTA in a 1:2 ratio did not realize a reversal of the enantiofacial differentiation.49,50

R

OH

Zn(OBut)4, ligand O Ph(Me2)CCOOH, MS 4Å R ligand(Zn(OBut)4/ligand)

R = Et (E)

R = Et (Z)

OH

R

(3S)

O OH (3R)

(R,R)-DBTA (0.2/0.22) (R,R)-DBTA (0.2/0.41) (R,R)-DIPT (0.2/0.22) (R,R)-DIPT (0.2/0.41)

92% 85% 90% 86%

87% ee (3S) 73% ee (3S) 82% ee (3S) 71% ee (3R)

(R,R)-DBTA (0.2/0.22) (R,R)-DIPT (0.2/0.41)

93% 45%

72% ee (3S) 49% ee (3R)

O HO HO

ð29Þ NHBn NHBn

O DBTA

These authors found that the presence and the type of molecular sieves also influenced the yield and enantiomeric excess. For example, in a 1:2 catalytic system of Zr(OBut)4 and DIPT, no epoxidation occurred without molecular sieves, and MS 4 A˚ (Nazeolite A) were the molecular sieves of choice over those with other pore sizes (MS 4 A˚, 71% ee; MS 5 A˚, 62% ee; MS 3 A˚, 32% ee). Molecular sieves might somehow play a key role in promoting the exclusive formation of the active catalyst. The reversed enantioselection could be ascribed to the differences in the structure of the zirconium complexes between 1:1 and 1:2 Zr(OBut)4/DIPT mixtures. To elucidate the structure of the complexes, they analyzed the Zr/tartrate complexes by 1H and 13C NMR, but the NMR spectra were too complex to be analyzed. Analyses by MALDI TOF MS showed the presence of a trimeric Zr complex from a 1:1 mixture and that of a monomeric complex from a 1:2 mixture. In addition, the use of a 1:1 Zr(OBut)4/DIPT catalyst showed a linear relationship between the optical purities of DIPT used and product, whereas the epoxidation using a 1:2 mixture exhibited a nonlinear relationship.

3.6.3.3

Tartaric Acid Esters for Other Various Types of Asymmetric Reactions

Chiral sulfoxides are important compounds that are finding increasing use as chiral auxiliaries in asymmetric synthesis and can be of interest to the pharmaceutical industry. Among the various ways to prepare chiral sulfoxides, the asymmetric oxidation of sulfides is one of the most attractive. The use of a hydroperoxide in the presence of a stoichiometric amount of various types of chiral titanium complexes derived from the Sharpless reagent allowed chiral sulfoxides to be obtained with enantioselectivities up to c. 90% ee.51 Kagan and coworkers found that the water-modified Sharpless titanium complex (Ti(OPri)4/(R,R)-DET/ H2O¼ 1:2:1) gave rise to very high enantioselectivities (greater than 99%). They revealed that the rate of addition of water was important to ensure reproducibility of the enantiomeric excess. The partial hydrolysis of the titanium alkoxide which formed reactive oligomers took place at the surface of water drops in dichloromethane. Because this is a two phase reaction, the size of the water drops, the mode of stirring, and the time of addition may well play an important role in the formation of the currently uncharacterized reactive titanium complex (equation 30).52

R

S

Ti(OPri)4, (R,R)-DET Ph(Me2)CCOOH, H2O Me R = Ph, Tolp, Anp, Bn,

O S R Me 77%, 99.2% ee 75%, >99.5% ee 78%, 99.5% ee 87%, 95.4% ee

ð30Þ

By the modification of Sharpless catalyst derived from Ti(OPri)4 and DIPT, enantioselective trimethylsilylcyanation of aldehydes was achieved by Hayashi, Oguni, and coworkers (equation 31). Addition of two equivalents of PriOH was required to realize high enantioselectivity. These workers observed that addition of PriOH served to simplify the 13C NMR spectrum of 1:1 of Ti(OPri)4 and (R,R)-DIPT complex, which might exist as complex aggregates in solution in the absence of PriOH.53

190

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

Ti(OPri)4 (0.2 equivalent) (R,R)-DIPT (0.2 equivalent)

O R

TMSCN

H

OH R

R = Ph, Anp, Thiophene,

CN

ð31Þ

84%, 91% ee 88%, 77% ee 84%, 83% ee

Jackson and coworkers reported that a magnesium tartrate complex, prepared in situ from Bu2Mg and (R,R)-DET, catalyzed asymmetric epoxidation of chalcones with ButOOH to give the corresponding epoxides with up to 94% ee (equation 32).54 Bu2Mg (0.1 equivalent) (R,R)-DET (0.11 equivalent) ButOOH

O Ar

Ph

O

O

Ar Ar = Ph Tolp Nap2

Ph

ð32Þ

61%, 94% ee 36%, 87% ee 46%, 92% ee

Hayashi, Oguni, and coworkers developed an asymmetric ring opening reaction of symmetrical N-acylaziridines with thiols catalyzed by (R,R)-DET-Et2Zn complex (equation 33). Based on 1H NMR observations, they assumed a four coordinated zinc complex to be the main active species in solution regardless of the molar ratio of the reactants (Figure 10).55 NO2 O N

NO2 (R,R)-DIPT (1.0 equivalent) Et2Zn (3.0 equivalent) ButC6H4S

4-ButC6H4SH (4.8 equivalent)

O NH

ð33Þ

98%, 93% ee,

RS H Zn

O

O

RS

H

O

OPri

H

H O

OPri

n

Figure 10 Proposed structure of zinc–thiolate complex. Reproduced from Equation 7 in Hayashi, M.; Ono, K.; Hoshimi, H.; Oguni, N. Tetrahedron 1996, 52, 7817–7832.

Ukaji, Inomata, and coworkers designed a novel chiral reaction system possessing multimetal centers utilizing tartaric acid ester as a chiral auxiliary.56 If reactants A and B were bound to two different metal centers M1, M2 of the dialkoxide, which was derived from tartaric acid ester, a rigid 5/5-fused bicyclic dinuclear bimetallic structure might be formed. In this structure, both reactants might be ideally oriented and activated by the metals, and the subsequent reaction might proceed in an enantioselective manner to afford the corresponding optically active products (Figure 11). Furthermore, the third metal M3 could potentially be assembled by coordination of ester carbonyl and alkoxide oxygens, and reactant C bound to M3 could take part in the reaction (Figure 12). Based on the concept, they developed several asymmetric cycloaddition and nucleophilic reactions. These authors first attempted an asymmetric Simmons–Smith reaction. When an allylic alcohol was treated successively with Et2Zn, (R,R)-tartaric acid ester, and second Et2Zn, the dinuclear intermediate 22 possessing an ethylzinc moiety might be generated. When diiodomethane was added to the dinuclear intermediate 22, the ethylzinc moiety might act as a reductant resulting in the formation of the bis-zinc species 23 containing an iodomethyl zinc moiety. An ensuing Simmons–Smith reaction within this complex was expected to proceed enantioselectively (Scheme 6). Actually, by the use of diethyl (R,R)-DET as a chiral auxiliary, the corresponding cyclopropylmethyl alcohols were obtained with enantioselectivity up to 92% ee.57 These authors then applied this strategy to the asymmetric 1,3-dipolar cycloaddition of nitrile oxides.58 When a hydroximinoyl chloride was added to the dinuclear species 220 , the ethylzinc moiety served as a base to generate the nitrile oxide in situ as

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

Reactant A

M1

Reactant B

M2

O

191

OR

O O

OR O

Figure 11 Dinucleating system utilizing tartaric acid ester. Reproduced from Scheme 1a in (a) Ukaji, Y.; Inomata, K. Synlett. 2003, 1075–1087. (b) Ukaji, Y.; Inomata, K. Chem. Rec. 2010, 10, 173–187, with permission from Wiley.

Reactant A

M1

Reactant B

M2

O

SH

O

Reactant C

O M3

OR O

Figure 12 Trinucleating system utilizing tartaric acid ester. Reproduced from Scheme 1b in (a) Ukaji, Y.; Inomata, K. Synlett. 2003, 1075–1087. (b) Ukaji, Y.; Inomata, K. Chem. Rec. 2010, 10, 173–187, with permission from Wiley.

R3 R1

OH

(i) Et2Zn (ii) (R,R)-DET (1.0 equivalent) (iii) Et2Zn

R2

R3 R1 R2

(iv) CH2I2

O EtZn O O Zn O 22

O I CH2 Zn R3 O O Zn R1 O 23 R2

OEt

OEt O OEt

R3 R1

OEt O

OH R2

up to 92% ee

Scheme 6 Asymmetric Simons–Smith reaction utilizing tartaric acid ester as a chiral auxiliary. Reproduced from Equation 1(a) in Ukaji, Y.; Inomata, K. Synlett. 2003, 1075–1087. (b) Ukaji, Y.; Inomata, K. Chem. Rec. 2010, 10, 173–187, with permission from Wiley.

depicted in Scheme 7. The subsequent 1,3-dipolar cycloaddition proceeded in a stereoselective manner to give the corresponding 2-isoxazoline with excellent enantioselectivity. Even when a catalytic amount (0.2 equivalent) of (R,R)-DIPT was employed, the 2isoxazolines were obtained with enantioselectivities of up to 93% ee when a small amount of 1,4-dioxane was added (equation 34).58b This method represents the first catalytic enantioselective 1,3-dipolar cycloaddition of nitrile oxides to alkenes.

R1

OH R2

(i) Et2Zn (ii) (R,R)-DIPT (1.0 equivalent) (iii) Et2Zn

R1 R2

(iv)

R3C(Cl)=NOH

O EtZn O O Zn O 22′

Cl O R3 C N O Zn O O Zn R1 O R2

OPri

OPri O OPri

N O OH

R3 OPri O

R1

R2

up to 98% ee

Scheme 7 Asymmetric 1,3-dipolar cycloaddition of nitrile oxides utilizing tartaric acid ester as a chiral auxiliary. Reproduced from Equation 2 in (a) Ukaji, Y.; Inomata, K. Synlett. 2003, 1075–1087. (b) Ukaji, Y.; Inomata, K. Chem. Rec. 2010, 10, 173–187, with permission from Wiley.

192

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid (i) Et2Zn OH (ii) (R,R)-DIPT (0.2 equivalent) (iii) R3C(Cl)=NOH 1,4-dioxane (1.5−2.5 equivalent)

N O OH

R3

ð34Þ

up to 93% ee

Asymmetric 1,3-dipolar cycloaddition of nitrones instead of nitrile oxides was also realized. The nitrones, possessing an amide moiety, were reacted with allylic alcohols by the use of a catalytic amount of (R,R)-DIPT as a chiral auxiliary to afford the corresponding 3,5-cis-isoxazolidines with high regio-, diastereo-, and enantioselectivities, up to 499% ee (equation 35).59

R1

OH

(i) Et2Zn (ii) (R,R)-DIPT (0.2 equivalent) (iii) I2

ArN O Pr2iN

(iv) pyridine N-oxide Ar Pr2iN N (v) O O

OH

ð35Þ

R1

O

up to >99% ee

Although many cycloadditions of nitrones possessing nitrogen and oxygen atoms were developed, the cycloaddition of 1,3dipoles bearing two nitrogen atoms was still limited. Ukaji, Inomata, and coworkers turned their attention to the development of enantioselective 1,3-dipolar cycloadditions of azomethine imines. They found that a magnesium-based catalyst system rather than the zinc-based system was able to realize the 1,3-dipolar cycloaddition of azomethine imines to afford the corresponding optically active trans-pyrazolidines with excellent regio-, diastereo-, and enantioselectivities (equation 36).60a,b The asymmetric 1,3-dipolar cycloaddition of azomethine imines to homoallylic alcohols was also achieved. The use of catalytic amounts of diisopropyl (R,R)tartrate as the auxiliary was also effective in the presence of MgBr2 (equation 37).60c

R N

(iii) H OH

(i) (R,R)-DIPT (1.0 equivalent)

N

O

O

ð36Þ

N N

(1.0 equivalent)

OH

1

(ii) R MgBr (3.0 equivalent)

R up to 96% ee

R R

(i) MgBr2 (1.0 equivalent) (ii) (R,R)-DIPT (0.2 equivalent) (iii) BunMgCl (1.5 equivalent)

1

(iv) H

N

N

O

O N N R1

(1.0 equivalent)

OH (1.1 equivalent)

ð37Þ

OH R up to 95% ee

The same concept was also applied to an asymmetric hetero Diels–Alder reaction of a nitroso compound61a,b and the asymmetric Diels–Alder reaction of O-quinodimethanes61c (equations 38 and 39).

HO

CO2But

HO

But

CO2

(1.0 equivalent)

(i) PrnZnBr (1.0 equivalent) (ii) Pri2Zn (1.0 equivalent) (iii)

Ph N

O OH

OH

(1.0 equvalent) (iv) PhN=O (1.5 equivalent)

ð38Þ H 91%, 92% ee

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

HO HO

CO2Pri

(1.0 equivalent)

(iii) X

(1.0 equivalent)

(iv) EtO2C

CO2Et (1.0 equivalent)

OH CO2Et

O O O BrMg Zn O O

OH

CO2Pri

CO2Pri

PriO

(i) BunMgBr (1.0 equivalent) (ii) Pri2Zn (1.0 equivalent)

193

X CO2Et

ð39Þ

up to 83% ee

EtO X CO2Et

The multinuclear catalyst system provided by the tartaric acid esters was found to effectively control the stereochemical course not only of the cycloaddition described above, (see Schemes 6 and 7, and equations 34–39) but also of the nucleophilic addition reaction of nitrones, in which an electronegative oxygen could both activate the CQN bond and strongly coordinate to metals. Thus the catalytic asymmetric addition of dialkylzinc to carbon–nitrogen double bond in 3,4-dihydroisoquinoline N-oxides was achieved by utilizing a catalytic amount of the magnesium, zinc mixed salt of dicyclopentyl (R,R)-tartrate to afford (S)-1alkyl-2-hydroxy-1,2,3,4-tetrahydroisoquinolines (equation 40).62 R1 RZnO

CO2Penc

BrMgO

CO2Penc

R2 R2

+ N _ R1 O (1.0 equivalent)

R2Zn (2.8 equivalent)

(0.2 equivalent) (Penc = cyclopentyl)

ð40Þ

R

Zn O R2 R2 O Br Mg N O O Zn Zn O R R R R

R1 R1

OPenc

R2 R2

R1

N

R1

OPenc

OH

R up to 95% ee

However, this system did not work well for the nucleophilic addition to acyclic nitrones such as N-(benzylidene)benzylamine N-oxide. These authors found that alkynylzinc reagent was the reagent of choice to give the corresponding optically active N(propargylic)hydroxylamines. During the addition reaction, a peculiarly dramatic enhancement of the enantioselectivity with time was observed. Ultimately, the addition of a product-like additive was employed to permit enhancement of the enantioselectivity to afford the N-(propargylic)hydroxylamines in high enantiomeric excess even in the case of the catalytic reaction (equation 41).63 MeZnO (i) MeZnO

CO2tBu

N

Bn O

Anp

Ph racemic (0.3 equivalent)

(ii) Me2Zn (1.0 equivalent)

N

Bn

(iii)

(iv) HC CR

Ar H (1.0 equivalent)

HO

(1.0 equivalent)

N

Bn

ð41Þ

Ar

MeZnO CO2tBu (0.2 equivalent)

up to 96% ee

R

Enhancement of the enantioselectivity by the addition of a product-like additive was again observed in the enantioselective addition of phenylzinc reagents to acyclic nitrones bearing an alkynyl substituent on the carbon to produce the same N(propargylic)hydroxylamines (equation 42).64 MeZnO (i) MeZnO

CO2

But

MeZnO CO2But (1.2 equivalent)

N

Bn

Bn

Anp

Ph racemic (0.2 equivalent)

(ii) PhZnMe (1.0 equivalent)

N

O

(iii) H R (1.0 equivalent)

Bn

N

OH

ð42Þ

Ph R up to 92% ee

194

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

A one-pot synthesis of optically active 4-isoxazolines was achieved by asymmetric addition of alkynylzinc reagents to nitrones utilizing di(t-butyl) (R,R)-tartrate as a chiral auxiliary followed by cyclization. By addition of dimethylzinc, the cyclization step was accelerated to afford the corresponding 4-isoxazolines with up to 93% ee (equation 43).65 MeZnO (i)

MeZnO MeZnO

(0.2 equivalent)

3.6.4

Bn

Anp

Ph racemic (0.2 equivalent) (ii) Me2Zn (1.0 equivalent)

CO2But CO2But

N

O (iii)

N

Bn

N

OZnMe

H Ar

Bn

Bn Ar

R

(1.0 equivalent) Ar H (iv) HC CR (1.0 equivalent)

ð43Þ

N O

(v) Me2Zn (3.2 equivalent)

R

up to 93% ee

Asymmetric Reactions Promoted by Tartramide–Metal Complexes

Tartramides are also useful chiral auxiliaries as are tartaric acid esters. Specific features unique to tartramides are as follows: (1) two substituents can be introduced on each nitrogen atom resulting in an amide moiety that is rather sterically demanding; (2) the coordination ability of the amide carbonyl oxygen is enhanced by delocalization of the lone pair of electrons on nitrogen; and (3) in the case of unsubstituted and monosubstituted amides, the acidic amide proton could play a role in the asymmetric induction. As described previously, Roush developed the allylboronate 12 containing a conformationally rigid bis-tartramide auxiliary rather than two tartaric esters that resulted in enhanced enantioselectivities of up to 95% ee.33,34 Yamamoto reported the asymmetric Diels–Alder reaction of naphthoquinone derivative juglone and a 1-siloxydiene in the presence of chiral boron reagent derived from B(OMe)3 and (R,R)-tartaric acid bis-3-toluamide as a model for the enantioselective preparation of important tetracycline natural products (equation 44). The high enantioselectivity observed for the tartramide type auxiliary can be ascribed to the novel intramolecular hydrogen bonding interaction between the hydrogen atom of the amide and the oxygen atom attached to the boron center. In accord with the observed stereochemistry of the cycloadduct, the diene approaches preferentially from the top face of the dienophile. The rate enhancement observed using the arylamide (X¼CONH(Tolm)) can be interpreted as resulting from the formation of a stronger hydrogen bond between the hydrogen atom of the amide substituted by electron-withdrawing aryl group and one of the oxygen atoms attached to the boron center (Figure 13).14,15 HO

OH

H

H N

N O O

O

OH

(1.2 equivalent) B(OMe)3 (1.2 equivalent)

O OSiEt3

O

OH

O

ð44Þ

H

H

OSiEt3

73% yield, 92% ee

R3SiO O

H R1

OO O B H H O N

N

O

R1

H O

Figure 13 Plausible transition state for the asymmetric Diels–Alder reaction promoted by chiral boron reagent. Reproduced from Compound 10 in Maruoka, K.; Sakurai, M. Fujiwara, J. Yamamoto, H. Tetrahedron Lett. 1986, 27, 4895–4898 and Scheme 1 in Yamamoto, H.; Futatsugi, K. Angew. Chem. Int. Ed. 2005, 44, 1924–1942.

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

195

Charette and coworkers developed a highly enantioselective process for the cyclopropanation of allylic alcohols using a bifunctional chiral dioxaborolane ligand 24 derived from (R.R)-N,N,N0 ,N0 -tetramethyltartaric acid diamide. Charette was the first to anticipate that a bifunctional, chiral ligand containing both an acidic and a basic site would allow simultaneous chelation of the acidic Simmons–Smith reagent and the basic allylic alcohol or its corresponding metal alkoxide. Thus, use of ligand 24 and the Zn(CH2I)2  DME complex generally afforded excellent results reproducibly providing substituted cyclopropylmethanol derivatives in high yields (480%) and enantioselectivities (up to 94% ee) (equation 45). The absolute stereochemistry of the resulting cyclopropanes was consistent with the model shown in Figure 14, wherein the reaction proceeded via three distinct steps. First, the zinc reagent deprotonated the alcohol to generate the corresponding zinc alkoxide. Second, the zinc alkoxide reacted with the dioxaborolane ligand in an irreversible fashion to generate the tetracoordinated boron intermediate, and third the olefin underwent an ‘amide-directed’ cyclopropanation reaction on the most stable conformation of the allylic alkoxide chain (Figure 14).66–69 I Me2NOC O O

H2 C

CONMe2 B

O

Zn O

O

Bu

H

N

H2C I

O

Me2N

O

B

O

H

Bu

I

Figure 14 Proposed transition state for the enantioselective cyclopropanation with chiral ligand 24. Reproduced from Figure 13 in Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103, 977–1050, with permission from American Chemical Society.

Me2NOC O R1

CONMe2 O B Bu 24 (1.1 equivalent)

R2

ð45Þ

R1

Zn(CH2I)2 (2.0 equivalent)

R2

OH

OH R3 up to 94% ee

R3

In the case of polyenes and allenes, chemo- and enantioselective cylopropanation was achieved at an allylic olefin. The cyclopropanation of chiral allylic alcohols proceeded diastereoselectively to afford anti-cyclopropylmethanol derivatives (equations 46 and 47).70–72 HO · R

R H R up to 97% ee

H

R1

OH R4

R2 R3

HO

24 (1.2 equivalent) Zn(CH2I)2·DME (3.0 equivalent)

R

24 (1.2 equivalent) Zn(CH2I)2 (2.2 equivalent)

R1

ð46Þ

OH R4

R2

ð47Þ

R3 anti :syn = up to >200:1

Charette and coworkers also developed the first enantioselective Simmons–Smith iodocyclopropanation reaction by the use of CHI3 instead of CH2I2. They attempted the iodocyclopropanation reaction using an a-iodozinc carbenoid to an allylic alcohol in the presence of the dioxaborolane 24. Employing a 2:1 stoichiometric ratio of CHI3 to Et2Zn, complete conversion was observed to afford the corresponding anti-iodocyclopropanes with up to 98% ee (equation 48). Transformation of the resulting iodocyclopropanes into the corresponding trisubstituted cyclopropanes, which are the versatile enantioenriched building blocks, was also demonstrated (Scheme 8).73

196

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

Ph

(ii) E+ (5.0 equivalent)

I Ph

OBn

(i) ButLi (2.2 equivalent) (ii) ZnBr2 (1.2 equivalent)

OBn

E+ = Ph2CO R = CPh2OH, 90% E+ = MeO2CCl R = CO2Me, 70%

R

(i) ButLi (2.2 equivalent)

Ar Ar = (EtO2C)pC6H4, 65% Ar = FpC6H4, 80%

Ph

(iii) ArI (1.2 equivalent) [Pd(dba)2] (5 mol%) PTolo3 (10 mol%)

OBn

Scheme 8 Functionalization of the iodocyclopropanes. Reproduced from Scheme 3 in Beaulieu, L.-P. B.; Zimmer, L. E.; Charette, A. B. Chem. Eur. J. 2009, 15, 11829–11832, with permission from Wiley.

(i) CH3I (4.4 equivalent) (ii) Et2Zn (2.2 equivalent) (iii) allylic alcohol 24 (1.1 equivalent)

R1 R2

R1

ð48Þ

R2

OH R3

I OH

R3 up to 98% ee

Recently, the same authors also found that the gem-dizinc reagent could be generated depending on the CHI3/Et2Zn stoichiometric ratio used. They developed the first asymmetric zincocyclopropanation of allylic alcohols. The reaction of the zinc alkoxide with the chiral ligand presumably generated a tetracoordinated boron species that reacted with the gem-dizinc carbenoid to produce the cyclopropylzinc. These species were found to undergo a boron-zinc exchange to generate the corresponding cyclopropyl borinate. As such, the stoichiometric enantiomerically pure ligand not only governed the enantioselectivity of the reaction, but also served as a stoichiometric boron source for the in situ generation of a very versatile Suzuki coupling partner. The resulting cyclopropyl borinate was much easier to handle than the corresponding cyclopropylzinc compound. As was the case with related intramolecular processes, the boron-zinc exchange proceeded in a stereoselective manner. Although the cyclopropyl borinate could in principle be isolated, a direct Suzuki–Miyaura cross-coupling reaction was effected. This methodology thus enabled the preparation of 1,2,3-trisubstituted cyclopropanes in good yields over two steps with good to excellent enantioselectivities (up to 97% ee) as depicted in equation 49 and Scheme 9.74 (i) Et2Zn (1.0 equivalent) (ii) 24 (1.2 equivalent) (iii) EtZnI·2Et2O (4.2 equivalent) CHI3 (2.1 equivalent)

R1 R2

R1 R2

OH R3

Bu B O

(iv) Pd(PPh3)4 (5 mol%) PhI (2 equivalent) KOH 3N (6 equivalent)

R1

Ph

ð49Þ

R2

R3

OH R3

up to 97% ee Me2NOC 24 R

OZnEt

CONMe2

O O B O Bu ZnEt

R

(IZn)2CHI

H R H

Bu B O

Me2NOC IZn O

B-Zn exchange R

H

CONMe2

O B O Bu ZnEt

Scheme 9 In situ boron–zinc exchange. Reproduced from Scheme 2 in Zimmer, L. E.; Charette, A. B. J. Am. Chem. Soc. 2009, 131, 15624–15626, with permission from American Chemical Society.

Charette’s group also developed an alternative method for the synthesis of 1,2,3-substituted cyclopropanes via a cyclopropanation of alkenes using zinc carbenoids generated in situ from diazo compounds and a zinc salt via aryl-substituted carbenoids. When the alcohol was treated with 1.0 equivalent of EtZnI and 2.5 equivalents of an aryldiazomethane in the presence of 1.1

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

197

equivalents of the chiral ligand 24, the corresponding 1,2,3-substituted cyclopropanes were produced with excellent diastereoand enantioselectivity (equation 50).75 CONMe2 O Bu B O O ZnI

(i) EtZnI R1

OH

R1

CONMe2

(ii)

Bu

O B

O

CONMe2

CONMe2 Ph

24

Ph Ph

CONMe2

CONMe2 Ph R1

O Bu B O O

N2

N2

CONMe2

O Bu B O O

R1

CONMe2

I

Zn

ZnI Ph Scheme 10 Proposed reaction mechanism for cyclopropanation. Reproduced from Scheme 3 in Goudreau, S. R.; Charette, A. B. J. Am. Chem. Soc. 2009, 131, 15633–15635, with permission from American Chemical Society.

O Bu

O B O

H

O Bu

NMe2

O H

H

NMe2

O Zn

H

I R1 Ph

R1

favored

O B O

O O Ph Zn H I

H

NMe2

NMe2

disfavored

Figure 15 Proposed transition state for the enantioselective cyclopropanation using zinc carbenoid. Reproduced from Scheme 3 in Goudreau, S. R.; Charette, A. B. J. Am. Chem. Soc. 2009, 131, 15633–15635, with permission from American Chemical Society.

(i) EtZnI (1.0 equivalent) (ii) 24 (1.1 equivalent) (iii) PhCH=N2 (2.5 equivalent) R1

Ph

ð50Þ R1 OH up to 99% ee

OH

The proposed mechanism for this reaction begins by the deprotonation of the alcohol by EtZnI followed by the complexation of the dioxaborolane ligand to the resulting zinc alkoxide on its addition (Scheme 10). Phenyldiazomethane then reacts with the zinc iodide salt to generate the phenyl-substituted carbenoid. This carbenoid was then delivered selectively to one of the two faces of the alkene by the dioxaborolane. The diastereoselectivity observed was rationalized by invoking favorable p-stacking, when R1 was aryl, and steric repulsion of the directing group (Figure 15).

N

I

H O N

H

O O

Zn

CH2

O B O Bu

Figure 16 DFT-computed structure of cyclopropanation transition state. Reproduced from Figure 4, TS-3A in Wang, T.; Liang, Y.; Yu, Z.-X. J. Am. Chem. Soc. 2011, 133, 9343–9353, with permission from American Chemical Society.

Using DFT calculations, Yu investigated the detailed mechanism and the origin of the stereoselectivity observed in the asymmetric Simmons–Smith cyclopropanation using the chiral dioxaborolane ligand 24 developed by the Charette group. Their

198

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

computational studies suggested that, under the traditional Simmons–Smith reaction conditions, the monomeric iodomethylzinc allyloxide generated in situ from the allylic alcohol and the zinc reagent had a strong tendency to form a dimer or a tetramer. The tetramer could easily undergo an intramolecular cyclopropanation to give the racemic product. However, when a stoichiometric amount of the Charette ligand 24 was employed, the monomeric iodomethylzinc allyloxide could be efficiently converted into a four-coordinated chiral zinc/ligand complex. The strong coordination of the carbonyl oxygen of Charette ligand 24 to the Zn(II) center played an important role in stabilizing this chiral zinc intermediate and suppressing the achiral background reaction. Examination of the transition-state structures permitted identification of the three key factors influencing the enantioselectivity: (1) the torsional strain along the forming C–C bond, (2) the 1,3-allylic strain caused by the chain conformation, and (3) the ring strain generated in transition states. For most allylic alcohols, the effects of these three factors on the enantioselectivity were synergistic, resulting in the generation of cyclopropylmethanols with high ee values (Figure 16).76

3.6.5

Miscellaneous

Tartaric acid skeleton provides various C2-chiral auxiliaries utilizing diol moiety, for example, by the reduction of carboxyl groups.1 Although this chapter is not focused on such chiral nonracemic compounds, DIOP and TADDOL, two of the most important derivatives among such compounds, are briefly discussed below. Kagan developed the tartrate-based diarylphosphine, DIOP, and applied this ligand to asymmetric hydrogenation of dehydroamino acids (equation 51).77 Although, asymmetric reactions utilizing DIOP itself did not realize so high levels of enantioselectivity, this pioneering work demonstrated that C2-symmetric diphosphine ligands may be quite useful for the asymmetric reactions employing transition metals. A large number of structurally modified derivatives were prepared with the aim of optimizing the efficiency of chirality induction by the ligand. Chiral DIOP-type ligands have been widely used for homogeneous asymmetric hydrogenation reactions of alkenes, imines, and reactive carbonyl compounds using either Rh(I) or Ir(I) catalysts. A recent successful example using DIOP is shown in equation 52.78 Ph

NHCOCH3

RhCl((−)-DIOP) H2

Ph

COOH

O

NHCOCH3 H COOH

PPh2 PPh2

O (−)-DIOP

95%, 72% ee

ð51Þ

Pd(OAc)2/ligand CO/H2 OH ligand (mol%)

O

O

ð52Þ

Pd(OAc)2 (mol%)

(+)-Tol-BINAP (4) (+)-DIOP (4) (+)-DIOP (8)

52% 83% 85%

1 1 2

53% ee 85% ee 90% ee

TADDOLs developed by Seebach are another class of extraordinarily versatile chiral compounds derived from tartaric acid. TADDOLs, which contain two adjacent diarylhydroxymethyl groups in a trans relationship on a 1,3-dioxolane ring, have been used as chiral auxiliaries for enantioselective reactions.79,80 Analysis of TADDOLS by X-ray crystallography revealed that the heteroatoms on the diarylmethyl groups were almost always in close proximity to each other, owing to hydrogen bonding, and are thus predisposed to form chelate complexes in which the metallic centers reside in propeller-like chiral environments. The TADDOL OH group that is not involved in intramolecular hydrogen bonding showed a strong tendency to associate intermolecularly with hydrogen bond acceptors (Figure 17). The process of crystallization led, enantioselectively, to the formation of inclusion compounds that lent themselves to the separation of racemic mixtures not otherwise suited to the classical method resolution via crystallization of diastereomeric salts. The high melting points of TADDOLs even made possible the resolution of racemates by distillation. Host–guest compounds formed between TADDOLs and achiral partners could also serve as platforms for enantioselective photoreactions. Ar Ar O O

O H O H Ar Ar TADDOL

Figure 17 Structure of TADDOL. Reproduced from Figure 40 in Yamamoto, H.; Futatsugi, K. Angew. Chem. Int. Ed. 2005, 44, 1924–1942, with permission from Wiley.

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

199

An example of enantioselective addition of diethylzinc to aldehydes using TADDOL is as shown in equation 53, which afforded either enantiomer simply by changing the reaction conditions. When 0.1 equivalent of a spirotitanate 25, which was stable in air for many hours and existed as a monomer in solution, was added to a mixture of Et2Zn and aldehydes, (R)-alcohols were produced (Method A). Alternatively, use of an additional amount of Ti(OPri)4 led to (S)-alcohols (Method B).81

Method A Et2Zn (1.2 equivalent) 25 (x equivalent)

O H MeO

OH * Et

Method B Et2Zn (1.2 equivalent) Ti(OPri)4 (1.2 equivalent) 25 (0.1 equivalent)

MeO

ð53Þ

Method A x = 0.05; 33%, 82% ee (R) 2.0; 89%, 98% ee (R) Method B 86%, 94% ee (S)

O

O

O

O

O

O

O

O

Ti

25

A highly enantioselective Diels–Alder reaction was developed by employing a chiral titanium reagent generated in situ from TiCl2(OPri)2 and TADDOL. With a catalytic amount of the titanium reagent, various acyloxazolidinone derivatives of a,bunsaturated carboxylic acids react smoothly with dienes in the presence of MS 4 A˚ to give the corresponding optically active Diels–Alder cycloadducts (equation 54).82 Ph Ph Ph Me CO2Me +

O

OH

O

OH

Ph Ph TiCl2(OPri)2 O

MS 4 Å

N

ð54Þ

CO2Me N

O

O

O

O 94%, 94% ee

O

TADDOL has also served as an example of Brønsted acid-assisted Brønsted acid catalyst (BBA), one of four types of ‘combined acids’.15 Rawal and coworkers reported that TADDOL itself catalyzed the all-carbon Diels–Alder reactions of aminosiloxydienes and substituted acroleins to afford the products in good yields with up to 92% ee, as well as catalyzing hetero Diels–Alder reactions (equations 55 and 56). This type of catalysis mimics the action of enzymes and antibodies in contrast to traditional, metal-based Lewis acid catalysts used in organic chemistry. TADDOL was expected to exist in a well-defined, internally hydrogenbonded arrangement. The dienophile, methacrolein, was expected to complex with TADDOL through a two-point interaction in which (1) the free hydroxyl group on TADDOL was expected to form a strong intermolecular hydrogen bond to the carbonyl group of the dienophile, providing the necessary lowering of the LUMO energy and (2) the complexed, electron deficient carbonyl double bond was expected to be stabilized through a putative p–p interaction with the electron-rich p system of the proximal equatorial 1-napthyl ring resulting in selective shielding of the re-face of the dienophile (Figure 18).83,84

H O

H

O O

H

O

O H

Figure 18 Proposed working model for the TADDOL-catalyzed Diels–Alder reaction. Reproduced from Figure 4 in Thadani, A. N.; Stankovic, A. R.; Rawal, V. H. Proc. Natl. Acad. Sci. USA 2004, 101, 5846–5850, with permission from PNAS.

200

Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

Ar Ar O

O H O H Ar Ar (20 mol%) O

TBSO +

H

Ph O

TBSO

Ph O

AcCl TBSO

Ar = 1-naphthyl

Ph

ð55Þ

O N

N

70%, >98% ee

Ar Ar O

TBSO +

CHO

O H O O H Ar Ar (20 mol%)

TBSO O CHO (i) LiAlH4

Ar = 1-naphthyl N

ð56Þ OH

(ii) HF N 83%, 91% ee

3.6.6

Conclusion

In summary, tartaric acid and its derivatives are essential chiral auxiliaries. Most specific feature that makes them to be utilized widely among so many auxiliaries might be the ready availability of both enantiomers at an easy rate. As described above, asymmetric reactions promoted by their metal salts of main group elements and early transition metals have been extensively studied. There is still room for development by utilizing late transition metals although DIOP is of course one of the solutions. Tartaric acid must be used more than ever especially when asymmetric reactions will be developed by achieving mastery of late transition metal complexes with tartaric acid derivatives.

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Acetogenin (Polypriopionate) Derived Auxiliaries: Tartaric Acid

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