МСОС Лекции с поиском и закладками

4. PeaKU,MM B1-1n111ra M XopHepa

4.1. PeaK4MR BtiTTMra

• Ma110-peaK4HOHHOCnoco6Hble (cra6H/1H3HpOBaHHble) H/1HAbl {R=C02R, CN, Ph) npeHMYI.J.\eCTBeHHO AalOT E-(TpaHc-) a11KeHbl

	e-.....		0
	0
MeiJn	I.:		\),._OEt
..
OEt		-OPPh3	E (mpaHC)-
	0
		Et
	TA cTa61t1nbHb1
	nnaHapHbllll
	oKcacpoccpeTaH

• <l>aKTOpbl B/1HRIOI.J.\He Ha COOTHOWeHHe Z/E-(41o1c-/tpaHc-) a11KeHOB B peaK4HM BMTTMra

	Z-(U.MC-) a11KeHbl		E-(TpaHc-) a11KeHbl
HeCTa6H/1H3HpoeaHHble H/1HAb1			CTa6M/1M3HpOBaHHble H/1HAbl
aK4enTOpHble 3aMeCTHTe/1M B <1>oc<1>1o1He			AOHOpHble 3aMeCTMTe/1M B <1>oc<1>1o1He
anpOTOHHblH paCTBOpHTe/1b			npoTOHHblH paCTBOPHTe/1b
OTCyYCTBMe AOn0/1HMTe/1bHblX coneH			A06asKa coneH (LiBPh4)
A06aBKa MRrKoro OCHOBaHHR (aMMHbl, i-)			H36blTOK >KeCTKoro OCHOBaHHR,
1			reHepHpYIOI.J.\ero H/1HA

4. PeaKU,MM BMnHra M XopHepa

4.1. PeaK4MA BMTTlllra

0

	H

	DCM
								'-::::::
	OH
	1. PBr3/Py							fl•KapOT"1H
PeT"1HOn						ee
	2.PPh3
	3. NaH/DMF
						PPhs

		H		..
			o	1.NaOH
		\		I 2. Ca(OH)i
0				3. NaBH4
		H	Cl
H	,&		T	H - H
-'(		-- •►_..J
)-	H

OH

H
	0	DIBAL
		►
''	0	-76°C
H					H
		H		H	0
OH	DCC/DMSO				H
		►

e0 Ph3P-

H

-.,

0

OH

H

_

1

4. PeaKU,MM BMnMra M XopHepa

4.2. PeaK4MM XopHepa - BaACBOpTa - 3MMOHCa - peaKU,litff Kap60HlitnbHblX COeAHHeHHM C aHHOHaMllt anK11tnq>ocq,0HaTOB, nplitBOARW,aff K o6pa30B3Hlitl0 anKeHOB

R1

>=O	+
R'

	O	-2(R3
	R		R
	O /bR
			'

	---'l►R1			R3
-----
-;;-\_.:			Rr=<		,
0-				R
	o
	-	R
OR

• anK11tnq,ocq>oHaTbl AOCrynHbl 1113 ranoreHonpOlit3BOAHblX III q,ocq>HTOB (peaKU,litff Ap6y3oea)

		R3	0
-			//
	.-- •► H P-.oMe
'-;..		lI
		R4	OMe
X-CH3

B(NaH)			R	3	0
			,\._//
-		►	01.		PI -oMe
	--11•
-BH			R4		OMe

• B peaKU,111111 XopHepa o6bl"IHO npeo6naAalOT E-(mpaHC)-anKeHbl (oco6eHHO C 3A R)

o

OR

0

o

0

2

o

o

--OR

P-OR

Medn..

HP...0R

.. R1

H

0

/

o

H

R

-

R1

II

_,(

®

e

2

bR ..

bR

.. >=<1

R

R2

R2

o

R

H

0-P

o

E (mpaHC-)

R

e

nnaHapHb1111

-

R

1

oKcacpoccpeTaH

OR

4. PeaKU.MM BMnMra 1,1 XopHepa

4.2. PeaK4MH XopHepa - BaACBOpTa - 3MMOHCa

•<l>aKTOpbl cnoco6cTBVtoW,He yaeJ1Hl.4eHMto AOJ1H E-(TpaHc-) anKeHOB a peaK4HM XopHepa:

cra6H/IH3MpoaaHHble 4>occ1>0HaTbl

reMneparypa peaK4HH 30°C > -7s0c

o6beMHblH P3AHKa/l B 3/lbAerMAe M ct>occt>opaHe

anpOTOHHblH pacrsopHTeJlb DME > THF

34>4>eKT KaTMOHa Lt+ > Na• > K•

Ph

0

Me	H
}--4;

N

,---:

0	0
	II	Ph
	P.-OR
RO	1: Me''"'
t-BuOK/THF/t.		E (mpaHc-)	R		Z («uc-)
		R=Me	5	.	95
		R=iPr	95		5

0 0

1. NaH/DMF

2. NaOH/H20

0

OH

AKpHBaCTI-IH

1

4. PeaKU,MM BMnHra M XopHepa

4.2.PeaKl.4Mli1 XopHepa - BaACBOpTa - 3MMOHCa

•,D,11R OO/IK4eHHff Z-(U.HC-) aKpHIIOBblX 3$Hpoe no peaKU,HH XopHepa HCOO/lb3VIOT

MOAH$HKaU,HIO Cr1111111a-,D,>KeHapH C 3A-ct,occt,oHaTaMH B YC/IOBHffX KHHeTH4eCKoro KOHTPO/lff

KN(TMS)2

)II,

THF/-78°C

,.,

00

o

,., R

0

R

H

R

V--QMe

OMe

o::::- -oCH2CF3

H

H

H

OCH2CF3

0 o

OMe

0- -0CH2CF3

KVIH8TVIY8CKVI KOHTponvipyeMbliA

OCH2CF3

CKOW8HHbliA OKCacj)occj)eTaH

0

0

Ph-{

Ph

H

H

KN(TMS)2

H

H

Z-90%, E-8%

18-c-6

Z-95%, E-2%

THF/-78°C

4. PeaKU.MM BMnHra M XopHepa

4.2.PeaK4MM XopHepa - BaACBOpTa - 3MMOHCa

•J3-Kero4>oc4>0HaTbl A3IOT B peaKl.,\MM XopHepa a,J3-HeHaCbllJ.\eHHble KeTOHbl

(HanpasneHHblM sapMaHT KpOTOHOBOM KOHAeHC31.,\MM Anff HeCMMMetpMYHblX KeTOHOB)

R1

3

0

0 o

R1

0 R3

)=

+

U-oMe

R

o

R

0'

,.,

2

R

4

bMe

R2

R4

02

(

0

2

-P

Me)

• CMHTe3 J3-Ketocf>occf>oHaTOB HeB03MO>KHO

nonyYaTb no peaKl.,\MMAp6y3osa O

o

o

••

o,--;,•(OMe¾

o

OMe

P

0

II

3

II'

g}+

I

o-P-oMe

P\

P(O

e)

Cl"\

M

-.:i►

J

\0M

II

"-oMe

r

,.,

e

•

ii- '....) P-o

e

OMe

,

-MeCI

Cl

6M . .

• A,nff nonyYeHMff

J3-Ketocf>occf>oHaTOB npMMeHfflOT 31.,\MIIMpOBaHMe3/IKM/lcf>ocoHaTOB

3

fl

B(NaH)

R

-<

0

0

R3 0 U-oMe _ _4

.x►

R

4JlYi,1.-e M

R

P.-OMe--,..)lo►

\

)lo

-

0

\

B

H

Me

......__ OMe

OMe

x

0

R3

0

-

0

0

0

0

II

to-OM

OEt

U-0Me

Ph

'-::::

H

Ph

1

0

NaH/DMF

OMe

OMe

NaH/OMF

P\

e

\

4. PeaKL\MM 81,1n1,1ra 1,1 XopHepa

Bz011,,.			"''''	1. HO OH			Bz011u,		··• '		O
			,,,,,,)=o	TsOH/PhH					.,,,,,"	X J
HO				2. PDC/DCM				0
											0
						1. AcOH H
1.NaBH4			HQ1111,		O						··•"'
	3..			11"		/THF			u
/CeCl					)
				:.,,				► THP0111
2.	K2C0					2.		DHP			,,,,,,
		3		"' X0					-
/MeOH			--=			/TsOH

- OTHP

0	1.PPh3	►	@	0	0
			3
Br ONa 2. NaHIDMF			Ph P

			0			0		Bz011u,
						}l-<>Et
--¢,		NaH/DMF				OEt			---
	1.
		0	0			-o
)=o	Ph P							Na	H011u,
	2. AcOH/H 0
		3		2
						-			OH
						-
								HQu,u

Na

OH

EtO	Et	'Br	0 0		0	C;,p,..oEt
		/	EtO	OEI	LiCI/DMSO/T	El / 'oEt..
		NaOEt			?-	Buli

.,,,,,"'"''){j

,\,,\\

.,,,,,

lllnonpocT

..,,,o

.,,,,,

PGl2

0

..

0 OH

3aKntO eHHe (P.S.)

HTOrH - B paMKax Kypca 6blnH pa3o6paHbl OCHOBHble MeTOAbl opraHHl.feCKoro CHHTe3a, npeHMYIJ.\eCTBeHHO opHeHTMpoeaHHble Ha XHMHIO 6AB.

8 u,enoM, HeCMOTpSI Ha orpoMHOe KOnH'4eCTBO H3BeCTHblX K HaCTOSIIJ.l.eMy epeMeHH peaKU,111111,V KOCTSIK coepeMeHHOHV MeAHU,HHCKHHV XHMHH COCTaBnsteT orpaHH'4eHHOe '4HCno

MeToAoe

Cone06pa3oeaHMe 12%

06pa3oeaHHe C-

C CBff3M 14%

-aHlt1HHble 8°/o -KaTlt10HHble 3% KpOCC-C04 2%

Ttianbl peaKU,HM

06paJoeaHMe

13% C-N CBff31,1

SN2 Ar- 7%

SN2 -4%

26%

		TpaHccpopMal.\Mff
		C02H rpynnb1
		- 8Ml,1,l],bl 10%
5%	15%	- 38l.1..\111THble 8%
06pa3oeaHHe	OKHCneHHe­
C-0 CBff31,1	BOCCTaHOBneHHe (5+10%)

Org. Biomol. Chem., 2006, 4, 2337; Organic Process Research & Development 2005, 9 (3), 253

3aKntolleHHe (P.S.)

TMnM HOe coepeMeHHOe neKapCTBeHHOe cpeACTBO

95% COAep>t<aTAr H/lH HetAr

90% HMetoT MOil. sec 550 (COOTBeTCTByeT npaBH/lY llHnHHCKH)

90% COAep>t<aT a30T

54% HMetoTXHpallbHblH '-'eHTP

B cpeAHeM CHHTe3 HaC4HTblBaeT 8 CTaAHM (OT 2 AO 15)

	C"1HTe3 x1,1pa11bHblX coeAMHeHMH
l,13 aCIIIMMeTp111'feCKlt1X
	lt1CXO.QHblX
	S5%	PaJAeneH111e
		CTepeOlt130MepoB
		30%

IllH.QYK41t1S1

5%

Ac111MMeTp1t1'fecK111111

aClt1MMeTplt1lt1	Clt1HTe3

Org. Biomol. Chem., 2006, 4, 2337; Organic Process Research & Development 2005, 9 (3), 253

3aKn10 eHMe (P.S.)

>70% COeAMHeHMM K3HAMA8TOB COAep>KaT reTepo4MKAbl

	KOMMep1.1eCKM AOCTynHble		CMHTe3Mp0B8Hbl ..
	MCXOAHble	N-reTepOI.IIIIKJlbl	reTepo4111Kn1113a41,1eM
	92%
			98%
	7%	O-reTepOL.1"1KJlbl	19%

np111MeHe 111e 331.1J.MTHblX rpynn

35% CoeA11tHeH111H-KaHA11tAaT0B c111HTea111py10T 6ea PG

AonR peaKU,MM ycTaHOBK111/yAaneH111R PG cocTaBnReT 6 111 15% OT scex cTaAMM

npo1.1111e	8%	3a1.14111THble rpynnbl		AMIIIHO-rpynnbl
			0
			..::--_47%	-Boe 19%
MepKanTorpynnb1	2%			-Cbz, Bn 13%
			".:..--- 29%
r111,qp0Kc111rpynnb114%--				Kap60Kc111-rpynnb1
OBn 5%; ArOR 4%

2 Org. Biomol. Chem., 2006, 4, 2337; Organic Process Research & Development 2005, 9 (3}, 253