МСОС Лекции с поиском и закладками

2. OKMCneHMe HeMeTann1,1 eCKIIIMM peareHTaMM

2.10. nepoKCMAbl M nepOKCMKMCnOTbl

2.9. HaAKHC/IOTbl BblCKOaKTHBHble OKHC/IHTe/lH AJIR 3nOKCHAHPOB3HHR 3/IKeHOB cy11bct,HAOB, KeTOHOB

0

OOH
OHCl MCPBA	HO

• 3nOKCIIIAHPOB3HHe 3/IKeHOB (peaK4HR npHne>t<aeea)

		0
		R -J/	0
R1LjR3		\DCMOOH	R''1 ,,,A"'R3
(7
R	R		2
2 4		-RC02H	R R4

• 3nOKCHAHPOBaHHIO cnoco6cTBYtOT ranToct,H/lbHble

rpynnHpOBKH B 3/1/IH/lbHOM 00/lO>KeHHH, pe3KL\HR 4YBCTBHTe/lbHa K CTepH4eCKHM TPYAHOCT.RM

OH OH

	nepeXOAHble COCTORHHR
		•
	Ar	•
		•
		'
	0	'
		'
		'
		'
	Q	'
		'
		'
		'
		.
		'
		'
		'
		'
		'
		'
		'
		'
		'
		'
		'
		'
		'
		'
		.
		•
		'
	lTc:c o·0-0	'	no(Pl_> n·c:e
		::
	(primary interaction)		(secondary)

I	MCPBA	"-:::::	MCPBA
	DCM		0'otBu	DCM
		o

2. OKHCJleHHe HeMeTaJ1JlH4eCKHMH peareHTaMH

2.9. HaAKHC/IOTbl

• 0KHC/1eHHe KeTOHOB H a/lbAerHAOB (neperpynHpOBKa 6aHepa - BH/1/IHrepa)

O

R-'<.

OOH

DCM

CKOpOCTb MHrpau.HH R2 : 3°C > 2°c > Bn, Ph > 1°c > Me

MHrpa4HR npOHCXOAHT c coxpaHeHHeM crepeOXIIIMHH a/1KH/1bHOH rpynnbl

0	O

MCPBA					MCPBA
	•
DCM			0		DCM ..
>- O MCPBA
	.,		[>-a-<: HO		HO
				.Qer11ApOaHAOCTepoH	TecronaKToH
DCM

• 8 apoMaTH4eCKOM PRAY MeTOA 34>4>eKTHBeH A/IR CHHTe3a «i,eH0/10B 0

AcCI	.,....-0--..,,,, '-:::	MCPBA	.,......o	.,....-o	0H
---►►t
ICl3	........... ........... 0-			--..,, '-:::
	0			....-...,,?,

2. 0KMC/1eHMe HeMeTa/1/lMl.feCKHMM peareHTaMM

2.10. 3nOKCMAMPOB3HMe annMnbHblX cnMpTOB (He 3aTparMeaeT M30nMpOBaHHble C=C)

• OKMCneHMe npoBOAAT TBHP B npMCYTCTBMM VO{AcAc)2 M/IM Mo02 (AcAc)2

:::::-...-OH

repaHll!OJ1 OH

TBHP

VO(AcAc)2

TBHPNO(AcAc)2
0 L		0	OH
	©
o-,,=v-		OH
0,
&'o-tBu
0/
I;;		0
		ee=97%

ACIIIMMeTpH eCKOe OKCMAHPOBaHHe (AE) no Wapnneccy

• 3HaHTMOCK/leKTMBHOe OKMC/leHMe anKeHOB npOBOAAT TBHP B npMCYTCTBMM

Ti{OiPr)4 M aCCMMeTpM Horo n11traHAa (+/-)DET M MS3A

			--
OH	0		OH	0
EtO		OEt EtO	.	OEt
		0	-
0	OH		OH
(·)-DET			(+)-OET

2. 0KHC/1eHHe HeMeTa/1/1"1'-leCKHMH peareHTaMH

ACHMMeTpM4eCKOe 3nOKCMAMPOBaHMe (AE) no Wapnneccy

• CTepeoxHMH"feCKHH pe3y11bTaT AE npeACKa3blBaeTCff no c11eAyt01.14eMy npaeH11y

[0]

( )-0

-

DE

(

O

OH

nepeXO.QHOe COCTOSIHMe

R2

·

T catJ

-)-

0

-

DET

TBHP

R2I'''A.,,,,,/

'PrO

r1"

I

HO

(

R1

R3

E

O --.

R1

+

R3

'PrO" ' ··....o....:=:·. _..o l' ) .

Ti(OPr)4'

►

MS3A

(+)-L-DET

R1

R3

0_...,... :·'o····

; '-....., R

-.I

\.---:,- E

6•

()

R2 ,,

.,,,11,

L--o_e_r_<caiJ

11

-6

[_O_J

o__o_H

RO

/

+

0

o

.11'

___,

f...:}.

·

O

T

OH

PNB-CI

, ,

OPN- __________

a-

TBHP

(

)-

-DE

,,,,,,

/

P

••,,,,I

1

:::::_

y

OH ;;

(R)rn1- -11..1111,o,on

Ti(OPr)4/

--

'"111

"

Tr-Cl

MS3A

(

)-L-OET

ti

OH

,.

+

'\7

NEt3

ee

92% (S)-fn1-11..11-1,o,on

0

N

N

F

TBHP

F

F

• ,:::,,-

•

Ti(OPr)4/

..

..

(+)-L-DET

no3aKoHa3on

31jF

MS3A

F

F

2. OK111cneH111e HeMeTann1111.1ecK111M111 peareHTaM111

2.11. ACMMMeTpM"leCKOe 300KCMAMPOB3HMe no ffKo6coHy-KaTCVKM

• OKMcneHMe 1,13on1,1posaHHblX C=C npoBOART AeHCTBMeM NaCIO B np111c'{TCTBMM Mn{ll1) 1,1 aCMMMeTpMYeCKIAX caneHOBblX KOMnneKCOB ((S,S)- 1,1n1,1 (R,R) -caneH)

[OJ Mn(ll1)-{S,S)-canett1

NaCIO

..

I

[0] (Mn(Hl)·(R.R)-caneH

Mn(lll)-(S,S)-caneH

npe,a.nono>KMTenbHblH MexaHM3M

3nOKCIAAMPOBaHMR no ffKo6coHy:

1

R'

0

0__)"--((

0Jf:;t11

N, v-0 'l_R- -

N, IV-0

N-Mn....._O

N-Mn...._o

Cl

I

Cl

Cl

Ph

NaCIO

0

OrpaHM\feHHe:

"=

Ph1"" ee=93%

Mn(Ill

)-(S,S)

-caneti

mpaHC- IA TeTpa-3aMell.\eHHble anKeHbl ,a.atOT

(S)·OKIIICb

HIA3KV10 CTepeoceneKTIABHOCTb

CT111po11a

Pa3Aen V

MeTOAbl cpopM111poaaH111H C-C 111 C=C CBH3ei:1

1. CMHTe3bl Ha OCHOBe MeTannopraHMLfeCKMX COeAMHeHMM

2. MeTOAbl KPOCC-COLfeTaHMR

3. MeTOAbl CMHTe3a anKeHOB

hchekotikhin

1.MeTOAbl no11y1.1eHHR peaKTHBOB rpHHbHpa

1.1.PeaKU.MA fpMHbApa

R-Hal	Mg	R-Mg-Hal	R= Alk, Ar, Bn, All
	Et20

(THF, PhOMe)

OrpaHHl.feHHe - Ha/1Hl.fHe B cy6crpaTe 11a6H/1bHblX <l>YHK4HH {C=O, CN, N02 HAP) H KHCJlblX npoTOHOB {OH, NH, SH, CH}

1.2. TpaHcMeTanni.tposaHi.te - o6MeH ranoreHa Ha Mera1111 MOC

>-MgCI MgCI

		N0	THF, -7a0c
2
			- i-Prl

1.3. MeTa1111i.tposaHMe - o6MeH BOAOPOAa Ha MeTa/111 MOC (peaKL4MA WopblrMHa)

Tl

Et-MgCI

R-::=--tlli Et20, -1a0c R-::=--MgCI

- EtH

2. MeTOAbl nony1.1eHHR nHTHHOpraHH'-leCKHX COeA.

2.1. PeaK4MR ranoreHonpOM3BOAHblX c nMTMeM

R-Hal 2Li ... R-Li R= Alk, Ar, Bn, All reKCaH

-LiHal

npoCTeMWllle noc (R= Me, Et, Pr, Bu, t-Bu, s-Bu, Ph) KOMMep eCKl,1 AOCTYnHbl.

2.2. TpaHcMeTann111poeaHMe - o6MeH ranoreHa cnoc (BuLi, t-Buli)

0

i

.o ►

B r

B

u

L

Li

1c

=-:1

"'

n

_

/(

5)>

2o, -

1s0c 1(

)>

2.

H

<±>

Et-BuBr

5

i

I Bu Li

L

1s0c

Et2-0,Bu-i

1/s		0
	1_ Ph--{		_..►
		H
----::,---.:.:"il
	2.H ©

HO>--Ph

• MR rpaHcMerann1-1poeaH111e anKHnranoreHHAOBnp111MeHRtoT 6onee c111nbHblM Merann111pyt0LJ.4111M areHT-t-Buli (2 eqv.)

R

'

r

t-BuLi

_

R

t-Buli

_'-""'

--t}

..

_'-""'

L,

./'

-Br] -

_.. I + I

B

,,,..___

Et20, -78°C

,,,..___ .

+ [,I

hchekotikhin

LiBr

2. MeTOAbl nony4eHMff nMTMHOpraHM4eCKMX COeA.

2.2. TpaHcMeTa1111MpoeaHMe - o6MeH ranoreHa c JlOC (BuLi, t-Buli)

Br	Li	0
2 t-BuLi		1.A
				..
N/4 Et2o, -1s0c	N/4		2.H (±)

• TpaHCMeTa/1/IHpoeaHHe IIYl.fWe npoTeKaeT B CMeCH Tp:tnna (THF/Et20/AmH (4:1:1) npM -110/-78°CoB 3THX YCIIOBHffX MO>KHO MeTa/1/IHPOBaTb cy6crpaTbl c 11a6HJ1bHblMH ct,yHKl,\HffMH (CO2, CN, NOz, 3nOKCHrpynnaMH)

0

				MeO	............,	H
			1.					OMe
	2 t-BuLi			MeO,,,.......		...		<?-		0KCOH
							N/4			...
N/4 Br Trapp mix		N/4	Li 2. H0					OMe
	-78°C							OH
	..,.__,, ....._,,,OMe						OH
'			HBr			-9' ... ..,,,		... N
/4		OMe			/4	,,,I.......
N					N			H	OH
0					0
									P11M11Tepo11
31

2. MeTOAbl nony1.1eHHR nHTHHOpraHHl.leCKHX COeA.

F	F 96%	<t>nyKoHa3on	F	70%

2.3. MeTa111111tpoeaHMe - o6MeH BOAOPOAa Ha MeTa/1/1 /lOC - KHC/IOTHO-OCHOBHble

B3aHMOAeHCTBHff CH-KHC/IOT C Buli, t-Buli

• PRA KHC/IOTHOCTl/1 CHKHC/IOT:								0
		Alk-H			Bn-H	AII-H
			C>-H	N-H			- H	Ar-H H
	60-50		s	-(	36 35	32
pKa			S 36	36			25 37-20 20

K111cnOTHOCTb CH·CBff31/l B03pacTaeT

• Buli H t-Buli - COOTBeTCTBYIOT CO/lffM caMblX C/la6blX KHC/IOT - BuH (pKa=SO), t-BuH (p a=60), no3TOMY HX HCnO/lb3VIOT A/lff MeTa/1/IHpoeaHHff APYfHX CH KHC/IOT

	Bu-Li +	I	I ., e I			+	Bu-H
					N
		ANI
					I
hchekotikhin		H	pKa 36		L" LOA		pKa 50