МСОС Лекции с поиском и закладками

3. roMoreHHOe KaTanMTMl.feCKOe rMAPMPOBaHMe

• Ha cKopocrb roMoreHHororMApHpoeaHHR npe>t<Ae ecero enHReT 3KpaHMpoeaHHOCTb ABOMHOH C8R3M. CTepH"leCKMe npenRTCTBMR CHM>t<atOT peaK4M0HHYt0 cnoco6Hocrb anKeHos

0

Pd/C/EtOH

H

Meo	(PPh3)JRhCI	Meo

A"c- H "3a ro ,..... H o o r a • 'lOBaH"1R:

-BblCOKaR CKOPOCTb, HH3KHe P, T

-CeJ'leKTMBHOCTb K crepM"leCKM He3aTPYAHeHHblM anKeHaM

-KaTanM3aTop He"ly8CTBMTeneH I< RAaM (-S-)

-B03MO>KHOCTb crepeOXHMH"leCKoro KOHTponR I}

3. roMoreHHOe KaTanMTM"leCKOe rMAPMPOBaHMe

A,,u1 crepeoceneKTBHoro roMoreHHoro ntApMposaHMR KOMnneKcaMM Ru M Rh pa3pa6oTaH PAA XMpanbHblX nMraHAOB (BINAP) AnR KOMnneKCOB nepeXOAHblX MeTannoe (P. Hoi:top1,1)

2

(R)-BINAP (S)-BINAP

SEaGulPHOS - accMMeTpM1.4HblH n1,1raHA eroporo noKoneHMJI (TaKacaro)

4 ,,,,,,,

,,,,,,

< ,,,,,,,,.,.

o

2

0 (RJ-SEGPHOS (S)-SEGPHOS

3. roMoreHHOe KaTanMTM\.leCKOe rMAPMPOBaHMe

• K0MnneKCbl Ha ocHoee py,-eHHA (Ru(OAch HllH RuCl3 ) *BINAP npHMeHAtoT AJIA rHAPHPOBaHHA ABOHHblX CBA3ei1 c ranTOcl>HllbHblMH rpynnaMH

OH Ru(OAch*	OH Ru(OAc)t
(S-)BINAP	(R-)BINAP
• KeT03cl>HpOB

H O	O	H2
	H
OEt u(OAc)i"
		(S-)BINAP

0	0	H2	H OH 0
II	II	►	%11-·. II
OEt		Ru(OAc)i"	OEt
		(R-)BINAP

• Kap60HH/1bHblX rpynn
H	OH
RLXRs		Ru(OAcho	Ru(OAch"
		(S-)BINAP	(R-)BINAP
		EDA	EDA

1

3. roMoreHHOe KaTanMTM eCKOe rMAPMPOBaHMe

• KaTanMTM'fecKMM U,MK/1 crepeoceneKTBHoro roMoreHHoro ntApMposaHMfl

Ct
I	(L = solvent)
p,Rt L

Ph, Cl

A)

20

3. foMoreHHOe KaTanMTH eCKOe rMAPHPOBaHMe

AcCMMeTpM HOe rMAPHPOBaHHe B CMHTe3e 11et<apcreeHHblX npenapaTOB

	OH
MeO	Ru(OAc)2•	Meo
	(S-)BINAP

H

OH

O O

c, 11 11 OEt

H2

► Ru(OAc)2* (S-)BINAP

c,

HOH

O	NMe3		\	H
	O	► N\!:,
	Et		//

O O	H2			►	Et	..
	OEtRu{OAc)2·
	(R-)BINAP

,PH

•.:-

O	NOHa				H
			\ G:'l .:,pH
		►	N
OEt			//		L-Car
		r		H
			N NH

O

e

0

	NHBz			ee = 98%NHBz
				de =88%						0 0
	0			H2		H,,. OH				F
			0
	11	oH		-		, OH
							•
				Cat	►					N
						/"-/		►►
	0.01% (R)-(RuCl(SEGPHOS))iCl3*NH2 Me2						ee = 98.5%;			/N 0
2	0.03% (R-)BINAP*Ru(OAc)i ee = 89%;									DesoqmOKCaL4V1H

3. roMoreHHOe KaTa/lMTM'-leCKOe rHAPMPOBaHMe

• KOMn/leKCbl Ha OCHOBe POAMR (Rh(CI04)*BINAP) npMMeHRtOT AJIR rMAPMPOBaHMfl

◄◄		H2				o		I		1
• -h- -							R2XR
	R	C	01	_*	)l				R
			_4							3
(S-)BINAP R4

fl Ph

H

H				O
	N
2
				0H
----1►
Ac				/t::.
		O/AcONa
	2		-

		O
Jl
..,...	O
Ph
	N	=./

\

O

H2

0

1.NaOH

►

Ph

R

P

h

·,, OMe

2.MeOH/HCI►

OMe

.CI04*

h

''

O

NH

(R-)BINAP O

NH

H

y

y

I

0.0002% cat.. ee 96%

I AcPheOMe

				0
			HO	OH
0	-►
			HO	NH2
			)Ir

L-DOPA

Pa3Aenlll

MeTOAbl BOCCTa HOB/leH L-1fl

4.BoccraHoeneHHe rHAPHAaMH

5.BoccTaHoeneHHe paCTBOPRIOW.HMHCff MeTannaMH

4.1. BoccraHoeneHHe rHAPMAaMH 6opa

1. rMAPMAbl 6opa

1.1. 6oprMAPMA HarpMJt (NaBH4).

•BOCCTaHae,uteaer Kap60HH/1bHble rpynnbl He 3aTparHBaR 3nOKCHAbl, HMTpo, HMTPM/lbl, en. a<J>Mpbl, Kap60KCaMMAbl, Kap60KCM rpynnbli

•anbAerMAbl e 100 pa3 6onee p.cn., 1.teM KeTOHbl;

•a,l3-HenpeAellbHble Kap60HHnbHble COeAHHeHMR MeHee p.cn.

0

OH

EtOH 0

KeTOH vt11aH.Qa-M111wepa

Ao6aeKM cyll.\eCTeeHHO enMsnoT Ha aKTHBHOCTb 6oprHAPHAa HaTpMst:

•	NaBH4/NiCl2	eoccraHaenMeaeT HHTpo (HHTpo3o) rpynnb1
		ArN02	.- ArNH2
•	NaBH4/TiCl4 soccTaHasnMeaeT en. a<l>Mpb1, Kap6oKcaMMAbl, Kap6oKCM rpynnb1
		RCO2X	• RCH2OH
		RCONH2	• RCH2NH2

• NaBHJCeCl3 (MeTOA /lywe) eoccraHaenMeaeT a,l3-HenpeAenbHb1e Kap60HMnbHble M KeTOHbl B npMCyYCTBMH anbAerMAOB

4.1. BoccTaHoeneHMe rMAPMAaMM 6opa

• NaBHJCeCl3 (MeTOA /lywe) eoccraHae1111eaeT a,'3-HenpeAeJ1bHb1e

Kap60HM/lbHble COeAHHeHMR

MeOH (NaBH(OMeb)

• ceneKTMBHOe BOCCTaHOB/leHMe KeTOHOB B npMCyYCTBMM 3/lbAerMAOB

	O NaB	H
	/2eoH
►	H

a-m1HeH

NaBH4' CeCl3 ►

2

4.1. BoccraHoeneHMe rMAPHAaMH 6opa

1.2. 6oprMAPMA nMTMfl (LiBH4 MnM 'in situ' NaBH4 /LiBr)

• 6onee p.cn 4eM NaBH4, BOCCTaHaenHeaeT Kap60HHnbHble rpynnbl, en. 34>Mpbl,

300KCMAbl, He 3aTparMBaR - HMTPM/lbl, Kap60KCaMHAbl, Kap60KCM, HMTporpynnbl;

0	0
	OEt	OH
OEt	H
	A1,1rJU1M/T
	AMrJU1MIT
		60%

1.3. '-'MaH6oprMAPMA HaTpMR (NaBH3CN) - p.cn. 3aBMCMT or pH

e npH Hei1rpa11bHblX pH MeHee aKTHBeH lfeM NaBH41 BOCCTaHaB/lHBaeT TO/lbKO MMMHO rpynnbl, He 3arparMBaff OCT3/lbHble 4>YHKL\MH BK/110\faff 3/lbAerMAbl. npMMeHRIOT AJ'lff BOCCTaHOBMTe/lbHOrO aMHHHpoeaHHff (MeTOA 6opxa)

()=a

0

HopaHa6aai-1H