Добавил:

fench Опубликованный материал нарушает ваши авторские права? Сообщите нам.

Вуз:

Казанский национальный исследовательский технологический университет

Предмет:

Химия

Файл:

The Nitro Group in Organic Synthesis

.pdf

Скачиваний:

170

Добавлен:

15.08.2013

Размер:

4.69 Mб

Скачать

☆

<<< < Предыдущая 1 2 3 4 5 6 7 8 910 / 3910 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > Следующая >>>

4.1

ADDITION TO NITROALKENES 71

Nef

Nu H+

NO2

(Chapter 6)

–

= RO

, RS

, RNH ,

NH2

carbanions

R2 = H

R2 (Chapter 6)

CNO

(Chapter 7)

(Chapter 6)

CH2NO2

NO2

X= COR, CO2R, CN,

SO2R, etc.

R2 = H

NH2

CNO

Scheme 4.1.

β-Nitro sulfides are conveniently prepared by simply mixing carbonyl compounds, nitroalkanes, and thiols in the presence of triethylamine.2 β-Nitro sulfide, which is used for synthesis of d-biotin, is prepared by this procedure (Eq. 4.2).3

	O
		+ CH3NO2 + HSCH2CO2H
H		CO2Me
		O

HO O NO2	HN	(4.2)
HO O NO2	HN	NH
	H	H
S	CO2Me	CO2H
	S	CO2H
		H
		d-biotin

Treatment of β-nitro acetates with thiols in the presence of base is also a simple method for the preparation of β-nitro sulfides (Eq. 4.3).4

72 MICHAEL ADDITION

	OAc	+ PhSH	THF		SPh	(4.3)
O2N		+ PhSH		O2N		(4.3)
			Et3N		~100%

β-Nitro sulfides are useful intermediates for the preparation of various heterocycles containing sulfur atoms. Synthetic applications are demonstrated in Schemes 4.25 and 4.3,6 in which biotin is prepared via cycloaddition of nitrile oxides (see Chapter 8).

(CH2)4CO2Me

S (CH2)4CO2Me

O2N

O2N O2N

80%

(CH ) CO

(CH2)4CO2Me

2 4

POCl3

1) Zn/Ag, (CF3CO)2O

2) Pd/C, H2

3) COCl2

81%

Scheme 4.2.

O2N

NO2

EtONa

Et3N

AcS

1) DMSO, Ac2O

N HN C

H2N

–

LiAlH4

2) NH2OH

1) OH

biotin

3) Beckmann

2) COCl2

rearrangement

Scheme 4.3.

Synthesis of thiopheno[3,4-c]isoxazoline is shown in Eq. 4.4, in which the Michael addition of allyl thiol to β-nitro enones and subsequent nitrile oxide cyclization are involved.7

Et3N

PhNCO

O2N

NO2

THF

Et3N

99%

82% (ds 71/29)

(4.4)

The base-catalyzed joint reaction of nitroalkenes with thiophenol in the presence of aldehydes gives γ-phenylthio-β-nitro alcohols in one pot (Eq. 4.5).8 The joint reaction of nitroalkenes with thiols and α,β-unsaturated nitriles (or esters) has also been achieved. (Eq. 4.6).9 β-Nitro sulfides thus prepared show unique reactivity toward nucleophiles or tin radicals. The nitro

4.1 ADDITION TO NITROALKENES

group can be replaced by various nucleophiles in the presence of Lewis acid.10 The reaction of β-nitro sulfides with tin radical gives alkenes, in which both the nitro and alkylthio groups are eliminated as shown in Eq. 4.7. Details of such substitution and elimination reactions are described in Chapter 7.

NO2

TMG

NO2 OH

+ PhSH + HCHO

(4.5)

TMG: tetramethylguanidine

SPh

88%

MeO

NO2

SEt

EtSH

MeO

NO2

Et3N

MeO

SEt

MeO

(4.6)

(Me2CH)2NH MeO

NO2

80% (ds 1:1)

Bu3SnH

Me3SiX

(4.7)

AIBN

TiCl4

NO2

X = H, CN,CH2=CHCH2

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at –78 °C gives anti-β-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of anti-β-nitro selenides (Eq. 4.9)12 and anti-β-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into β-amino alcohols with the retention of the configuration, which is a useful method for anti-β-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the β-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14

Me Me

Reagent and condition

Yield (%) anti/syn

NO2

PhSLi, –78 ºC, AcOH

91/9

NO2

PhSH, Et3N, RT

40/60

SPh

(4.8)

74 MICHAEL ADDITION

NO2

AcOH

(4.9)

PhSeNa

–78 ºC

NO2

SePh

68% (syn/anti = 91/9)

NO2

NH2

PhCH2ONa

Pd/C, H2

AcOH

EtOH, HCl

NO2

OCH2Ph

–78 ºC

73% (syn/anti = 91/9)

72% (syn/anti = 91/9)

(4.10)

Enantioselective synthesis of β-amino alcohols is also reported by the application of the oxa-Michael addition to nitroalkenes (Eq. 4.11). The sodium salt derived from (1R,2S)-N- formylnorephedrin and NaH reacts with nitroalkenes at –78 °C with high diastereoselectivity (de: 93–98%) in good yields. Virtually diastereomerically pure compounds can be obtained by using column chromatography. After the reduction of the nitro group to the amino group, the cleavage of the ether with sodium in liquid NH3 at –78 °C leads to amino alcohols without racemization.15

NHCHO

1) NaH, –78 ºC

H N

NO2

2) AcOH

NO2

66% (de 94%)

1) NaBH4, Pd/C

Na/ NH3

NHBoc

2) Boc2O

–78 ºC

→ NHBoc)

75% (ee 96%)

80% (NO2

(4.11) The Michael addition of alkoxides to nitroalkenes gives generally a complex mixture of products due to the polymerization of nitroalkenes.16 The effect of cations of alkoxides has been examined carefully, and potassiumor sodium-alkoxides give pure β-nitro-ethers in 78–100% isolated yield (Eqs. 4.12 and 4.13).17 When lithium-alkoxides are employed, the yields are

decreased to 20–40%.

					Ph
OH		1)	Ph	NO2	NO2	(4.12)
	KH, THF		Ph		O	(4.12)
	KH, THF				O
	RT	2) 1 N-HCl
					80%
					NO2
OH	NaH, THF	1)	NO2		O
OH	NaH, THF	1)	NO2			(4.13)
	RT	2) 1 N-HCl				(4.13)

94%

4.1 ADDITION TO NITROALKENES

The Michael addition of oxygen-nucleophiles followed by subsequent cyclization or cycloaddition provides an important method for the preparation of oxygen-heterocycles such as tetrahydrofurans. For example, 3-nitro-2H-chromenes bearing various substituents are prepared by the reaction of substituted salicylaldehydes with nitroalkenes (Eq. 4.14).18a The reaction with nitroethanol in the presence of di-n-butylammmonium chloride in refluxing isopentyl acetate gives 2-unsubstituted 3-nitro-2H-chromene in 50% yield.18b Some 3-nitro-2H-chromenes display efficient optical second harmonic generation for nonlinear optical applications.19

CHO

NO2

1) Et3N, RT

(4.14)

NO2

O Ar

2) Al2O3

	R1, R2 = H, Cl, OMe	70–84%
	Ar = Ph, p-MeOC6H4, 2-thienyl	70–84%
	Ar = Ph, p-MeOC6H4, 2-thienyl

The Michael addition of allyl alcohols to nitroalkenes followed by intramolecular silyl

nitronate olefin cycloaddition (Section 8.2) leads to functionalized tetrahydrofurans (Eq. 4.15).20

t-BuOK

NO2

Me3SiCl

–98 ºC

NO2

OSiMe3

OSiMe

Bu4NF

74%

(tandem reaction)

(4.15)

Recently, tandem (domino) Michael addition initiated by oxygen nucleophiles has received much attention for the construction of octahydrobenzo[b]furans. The reaction of 1-nitrocyclo- hexene with 4-hydroxy-2-butynoates, catalyzed by t-BuOK at 0 °C, gives the desired furan in 90–100% yield (Eq. 4.16).21 Similarly, 4-chlorobut-2-yn-1-ols (Eq. 4.17)22 or prop-2-ynyl alcohols (Eq. 4.18)23 react with nitroalkenes in the presence of t-BuOK to give the furans. Anionic domino transformations induced by the addition of alkoxides to nitroalkenes proceed with high diastereoselectivity due to allylic 1.3-strain.22 The reduction of the nitro group in the products of Eq. 4.18 with SmI2 affords 3,6-dihydro-1,2-oxazines (Eq. 4.19). The cleavage of the N-O bond of the product generates 1,4-bifunctional groups.24a The [2,3]sigmatropic rearrangement of the allylic nitro compounds is also possible.24b Such anionic domino transformations have been reviewed.25

				CO2Me
NO2				O2N
NO2	+	HO	t-BuOK
		HO	t-BuOK	(4.16)
		CO2Me	0 ºC	(4.16)
		CO2Me	0 ºC	O
				H

100%

76 MICHAEL ADDITION

NO2	+	HO		t-BuOK
			Cl	0 ºC

NO2	+		t-BuOK
			t-BuOK
			0 ºC


		HO

	O2N	•
	O2N	SmI2
		SmI2
	H	O
	H

		O2N	•
		O2N
			(4.17)
		H	O
		H
		70–78%
O2N			O2N
			+
H	O		O
H			H

78% (5-exo/6-endo = 1.7/1) (4.18)

(4.19)

60–90%

The addition-elimination reaction of hetero-atom-substituted nitroalkenes provides functionalized derivatives of unsaturated nitro compounds.26 Nitroenamines are generally prepared from α-nitro ketones and amines (see Chapter 5 regarding acylation of nitro compounds).26

The addition of alkoxides to 2-nitro-1-phenylthio-1-alkenes affords β-nitro-aldehyde acetals.27d The reaction of the same nitroalkenes with amines gives nitroenamines.27c They are important intermediates for organic synthesis and are generally prepared by the reaction of nitroalkanes with triethylorthoformate in the presence of alcohols or secondary amines.27a–c The methods of Eqs. 4.20 and 4.21 havesomemeritsover theconventionalmethods,forvariouslysubstitutedβ-nitro-aldehydes acetals or nitroenamines are readily prepared by these methods.

PhS	+			THF		N	(4.20)
NO2	+		N	RT, 2 h			(4.20)
NO2			N	RT, 2 h			NO2
			H				85%
							85%
				MeO		NO2
PhS		MeONa		MeO		NO2	(4.21)
		MeONa

NO2		RT, 24 h			H
					78%

Interesting push-pull dienes, 1-dialkylamino-4-nitro-1,3-butadienes, are prepared by the application of this addition-elimination reaction. (Eq. 4.22).28

PhS	+		CH2Cl2	N
		N	RT		(4.22)
	NO2			NO2
		H		80%

A new synthesis of β-nitroenamines by amination of nitroalkenes with methoxyamine in the presence of base is reported (Eq. 4.23).29

		4.1	ADDITION TO NITROALKENES			77
		H2NOMe	Ph		H
Ph	NO2		H N		NO	(4.23)


		t-BuOK
		t-BuOK	2	2
			94%

The Michael addition of a nitrogen-centered nucleophile to nitroalkenes affords compounds that may serve as precursors of vicinal diamines, since the nitro group can be reduced to an amino function by reduction. The very convenient method for the preparation of 1,2-diamines is developed by the addition of O-ethylhydroxylamines to nitroalkenes followed by reduction with H2 in the presence of Pd/C (Eq. 4.24).30

					NH2
1		NO2	1) EtONH2•HCl, NaHCO3, THF	R1	NH2
R					(4.24)
		2	2) H2, Pd/C, EtOH		R2
		2	2) H2, Pd/C, EtOH		R2
	R
					54–90%

The conjugate addition of chiral-nitrogen nucleophiles to nitroalkenes provides access to chiral compounds having nitrogen functionalities on vicinal carbon atoms. Various natural products belong to this class of compounds such as biotin, penicillin, and several amino acids that are components of the peptide antibiotics. Chiral nitrogen nucleophiles, (S)-2-methoxymethylpyrrolidine (SMP) and its enantiomer (RMP) have been used for this process.30 Fuji and Node developed an elegant method for asymmetric synthesis using (S)-2-methoxymethylpyrrolidine and nitro enamines,118 which is discussed in Section 4.2 (Eq. 4.25).

			OMe
O N	+	THF	(4.25)

NO2	N	RT	N
	H OMe
			NO2

Amino alcohols like (S)-prolinol react with nitroalkenes very rapidly with very high facial selectivity.31 Rapid and stereoselective reduction of the nitro function is essential for the conversion of the products to 1,2-diamine derivatives with the retention of the configuration. Samarium diiodide is recommended in the stereoselective reduction of thermally unstable 2-aminonitroalkanes to give a range of useful 1,2-diamines (Eq. 4.26).32

NO2

CH2Cl2, RT

30 min

NO2

NH2

SmI2

(4.26)

MeOH-THF

95% (trans/cis = 99/1

90%

facial selectivity = 97/3)

78 MICHAEL ADDITION

The asymmetric synthesis of 1,2-diamines using (2S,3R,4R,5S)-1-amino-3,4-dimethoxy- 2,5-bis(methoxymethyl)pyrrolidine with high enantiomeric excess (93–96% ee) has been developed, as in Eq. 4.27.33

MeO	OMe
MeO		Me	NO2
MeO	OMe		NO2
N		–78ºC→20ºC
NH2		–78ºC→20ºC
NH2
	MeO	OMe
		OMe
MeO			NH2	(4.27)
	N H		Raney Ni, H2	NH2
MeO		N	Me
MeO		NO2	70% (ee 96%)
	Me	NO2	70% (ee 96%)
	Me
	75%

The conjugate addition of (R)- or (S)-4-phenyl-2-oxazolidinone to nitroalkenes is catalyzed by t-BuOK at –78 °C to give the addition product with excellent diastereoselectivity, the products are converted into vicinal diamines (Eq. 4.28).34

NO2

t-BuOK, THF

NO2

–78 ºC, 15 min

NHAc

75% (ds 98%)

1) HCO2NH4, Pd/C

NHAc

(4.28)

2) Li/NH3

3) AcCl

46%

An alternative method for the stereoselective preparation of 1,2-diamines is shown in Eq. 4.29, in which the addition of nitroalkanes to imines is used as a key reaction.35

1) n-BuLi, –78 ºC, THF

EtCH2NO2 +

OMe

2) AcOH

MeO

1) SmI2

(4.29)

THF-MeOH

2) CAN

NH2

NO2

MeCN-H2O

anti/syn = 10/1	RT

The products of the conjugate addition of (R)-4-phenyl-2-oxazolidinone to nitroalkenes are converted into D-α-amino acids with high enantiomeric purity (Eq. 4.30).36

4.1 ADDITION TO NITROALKENES

NaNO2, AcOH

O N Ph

DMSO, 40 ºC

NO2

O	O		Ph			NH2
	O
	N

			1) Li/NH3			CO2H	(4.30)
			1) Li/NH3				(4.30)

		CO2H 2) DOWEX
		CO2H 2) DOWEX
				50W-X4-400
	51%				62% (96% ee)

An intramolecular Michael type reaction of a nitrogen nucleophile to nitroalkene, as shown in Eq. 4.31, provides a useful method for the preparation of 2,2-dimethyl-1-carbapenam.37

		H
NSiMe3	KF	N	(4.31)
	0 ºC	N	(4.31)
	0 ºC	O
O	NO2		NO2
	NO2	78%	NO2
		78%

The Michael addition of phosphine nucleophiles to nitroalkenes provides novel β-nitro phosphonates, as in Eq. 4.32.38 Yamashita and coworkers have shown that the nucleophilic addition of Ph2POH to chiral nitroalkenes derived from sugars proceeds stereoselectively to the 5-(S)-isomer (Eq. 4.32) in high diastereoselectivity (ds 11:1).

NO2				NO2
NO2		O		O
O	O	Ph2PH	H PPh2		(de = 11:1)	(4.32)
	O			O	(de = 11:1)	(4.32)
			H	O
MeO	O		H
	O			O
			MeO

The base-catalyzed reaction of dialkyl phosphite with nitroalkenes results in the formation of alkenyl phosphonates (Eq. 4.33).39

				O
Ph	Me
Ph	Me		Et3N	(MeO)2P	Me
	+	(MeO)2P(O)H			(4.33)
					(4.33)
			THF
H	NO2		THF	Ph	H
H	NO2			Ph	H

72% (E/Z = 3/1)

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of β-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite β-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of

80 MICHAEL ADDITION

the sulfoxide (Eq. 4.34).40 The selective reduction of β-nitrostyrenes to β-aminostyrene derivatives provides a direct method for the preparation of the same enamides, but the reduction of nitroalkenes leads to a formation of complex products involving carbonyl compounds (see Chapter 6).

MeO

CH3NO2, PhSH

CHO

Et3N

MeO

NO2

1) Zn/HCl

(4.34)

2) HOCOCOCF3

PhS

3) NaIO4

NHCHO

82%

53%

1-Nitro-2,2-bis(methylthio)ethylene is a useful reagent for the preparation of various heterocycles, which is described in Chapter 10.

4.1.2 Conjugate Addition of Heteroatom Nucleophiles and Subsequent Nef

Reaction

Barrett and coworkers have explored hetero-substituted nitroalkenes in organic synthesis. The Michael addition of nucleophiles to 1-alkoxynitroalkenes or 1-phenylthionitroalkenes followed by oxidative Nef reaction (Section 6.1) using ozone gives α-substituted esters or thiol esters, respectively.41 As an alternative to nucleophilic addition to 1-(phenylthio)-nitroalkenes, Jackson and coworkers have used the reaction of nucleophiles with the corresponding epoxides (Scheme 4.4).42 Because the requisite nitroalkenes are readily prepared by the Henry reaction (Chapter 3) of aldehydes with phenylthionitromethane, this process provides a convenient tool for the conversion of aldehydes into α-substituted esters or thiol esters.

1-(Benzyloxy)nitroalkene is useful for the synthesis of bicyclic β-lactam systems and has been applied for the construction of an oxapenam (Eq. 4.35).43 Desilylation and cyclization take place on treatment of N-silylated nitroalkene with Bu4NF to give the nitronate of the bicyclic β-lactam, which is treated with ozone in situ to give the benzyl ester of oxapenam. When (phenylthio)nitromethane is used instead of (benzyloxy)nitromethane, the phenylthio ester of oxapenam is obtained (Eq. 4.36).44

NO2

60–80%

X = O, S

N , CH(CO2Me)2

Nu = OMe,

NO2

t-BuOOLi

Scheme 4.4.

<<< < Предыдущая 1 2 3 4 5 6 7 8 910 / 3910 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > Следующая >>>

Соседние файлы в предмете Химия

#
15.08.20138.95 Mб26The Gale encyclopedia of science. 3 edit. Vol.3.djvu
#
15.08.201310.22 Mб23The Gale encyclopedia of science. 3 edit. Vol.4.djvu
#
15.08.20139.52 Mб25The Gale encyclopedia of science. 3 edit. Vol.5.djvu
#
15.08.20138.79 Mб27The Gale encyclopedia of science. 3 edit. Vol.6.djvu
#
15.08.20131.06 Mб56The LANL Periodic Table of Elements, with Descriptions.pdf
#
15.08.20134.69 Mб170The Nitro Group in Organic Synthesis.pdf
#
15.08.20134.7 Mб82The Nitro group in organic sysnthesis - Feuer.pdf
#
15.08.2013111.8 Кб11The Suzuki-Miyaura cross-coupling reactions of 2-, 6- or 8-halopurines with boronic acids leading to 2-, 6- or 8-aryl- and alkenylpurine derivatives (Martina Havelkova, Dalimil Dvorak, Michael Hocek).pdf
#
15.08.20133.28 Mб29Tools and Applications of Biochemical Engineering Science.pdf
#
15.08.201342.78 Mб15Vanderah Chemistry of Superconductor Materials.pdf
#
15.08.201314.63 Mб65Vankka J. - Digital Synthesizers and Transmitters for Software Radio (2000)(en).pdf