МСОС Лекции с поиском и закладками

2.MeTOAbl nony4eHH.R /1HTHMOpraHH4eCKHX COeA.

2.3.MeTa1111111poeaH111e - o6MeH BOAOPOAa Ha MeTa/1/1 /lOC

0

		BuLi		Li	1.Ph Ph				Ph
	/4	THF/-78°C	/4					/4	Ph
							(±)
	N		N			2. H		N
								H	nepreKc1,11u.1H

(

• aKTHBHOCTb Buli 3aBHCHT OT CTeneHH 0/1HrOMepHOCTH (Buli) , n 3aBHCHT OT p-llff

= = = n

n 8(reKCaH), n 6 (Et20), n 2 (THF), - l.leM MeHbWe n, TeM BblWe aKTHBHOCTb. Pa3pyweHHIO acco411aTOB Bbl3blBalOTxenaTHPYIO He areHTbl (TMEDA, HMPA, DABCO)

Bu-L

	I
i)	N
	+ /
n	'-N

TMEDA I

)

..

\N/

L1

N/

/ \

Pr \ /

N

L1 ',,•' 'N

Pr I

I \

_,

•

\ /	Pr
N	,
.
L
''-,'
N	I

/ \ Pr

IPh-H

Bu-Li

TMEDA/THF Ph-Li

RT,3h

· Bu-H

• MeTa/1/lHposaHHe reTepo4HK/1Hl.leCKHX COeAHHeHHH	0	..
		Bu-Li
	N		N	Bu
		2 t-Bu-Li	Li
	N/40 Br	Et20, -78°C		N/4 Li

2. MeTOAbl nony"leHMff nMTMHopraHM"leCKMX COeA.

2.3.MerannMpoaaHMe

•3aMeCTHTeJ1H, xenaTHPYIOU,\He LiOC (DMG), cnoco6cTBYIOT MeTallllHpOBaHHIO e opmo-(DOM)

DMG:

Bu-Li

• Bu-H

F

Bu-Li...

THF/Et20

• Bu-H

F F

	s
	..
OMG:\.	0
	0
" 6-	:c
Li	m
	s
	IO
	s
	G)
	:c
_,.....o,	s
	:c
Me	0

Li 1. CO2

..

2.H(±)

F 0	NHBoc 1. t-Bu-Li			BocHN 0
OH MeO	THF/Et20 .790c			Meo	OH

F

			0					0 OH 0
I	s-Bu-Li				N/ s-Bu-Li			'N
	THF/Et20				I			I
						THF/Et20
Ct	-1a0c					-78 to o0c			56%
	• Bu-H	Cl 77%		Cl				Cl

2. MeTOAbl nony4eHMff nMTMHOpraHM4eCKMX COeA.

2.3. MeTann111poeaHMe
				'h
N 0	1. s-Bu-Li		1. s-Bu-Li	N 0
	THF		THF/TMEDA	I ll
	-1s0c		-1a0c
	2. Mel		2. Mel

• A11ff MeTa1111111poeaHMff a PffAe c11y aee (np111 Ha/lM MM 11a6M/lbHblX K Buli <l>VHKL\MOHa/lbHblX rpynn) MCnO/lb3VtOT aMMAbl /IMTMff (LOA, LTMP)

0 LDA	0	LTMP
N@	N<±>
Li	Li

0....,_..,,, N(i-Pr)2

	LOA				Li
			s-Bu-Li
I THF/-1a0c			THF/TMEOA		/2
			-1a0c		N

71 Li

2. MeTOAbl nony4eHMR 11MTMHOpraHH4eCKMX COeA.

2.3. MeTann1i1poeaHMe

				1/
				s
I	o 1. s-Bu-Li			I
/N			,.,..N ___,...,.....o
MeO ,::;,-	THF/TMEDA -78°C Meo			,::;,-
		2. Mel
::::,.__				::::,.__
		OMe 0

OH		2 LOA			LiO	• •	1. CO2
				0c
	Et20/-7a
								0
					\N	0	OH
							1. NaOH/
					MeO		OBn	...
2.		0		OBn				2. HCI
H				o,,..._,._Me OH		0	OMe

0	H
,,,.._..___,,.'-=:::: OBn 2. BCl DCM -780C
I ll Me	Q)MJ10AYllbUt11H ll OMe

• LTMP H LOA HCnonb3VtoT AJlR reHepau,HH eHonRTOB

\___J;O

OH

_	2LD	A	►
		-t1•
Et20/-78			C
			°

OLi

r;OLi

	OLI	BzCI	0
LTMP			OEt
Et20/-78°C	OEt
			90%

0	Ph

2.HI;?;}

3.CMHTe3bl Ha ocHose MOC

3.1.nony'feHMe Kap6oHOBblX KHCnOT M MX npoM3BOAHblX

R-M

R-M

0

X=CI, OR

1. O=C=O

x.....II

'z

2.H(±)

C

S

.. 0

1.

Z=OR, NR2

0

20/-78oC

0

2

°

1.LDA ..

:-) TAPI

Bu-Li

Et

Sn

THF/Et 0/ RT C

O

S

DCM

Eto-

0

2. Cl-c"1

.,;c::::::,Q

2.

c"

1

'osnBnO

\

3.2. no11Y'feHHe 6opOHOBblX KHC/IOT H HX npOH3BOAHblX

B(O )

,

H 0

-

R 3

oR

2

--- R-B

R M

o

©

R= Me, Et, i-Pr

Li

' R

H

Br

O

p-1--

Bu-Li

M eo - so'

►

/0'-L-.-

C ,,......

_ __

____

c:>----{ -

B

.,

Et20/-78°C

'o--"-Kpoc-coYeTaH e

O

OTHP

Bu-Li

F

F

?"' ---- °

Cy3yK\11

F

I

OTHP 1. B(OMe)

I

Br

Li

2. H20/HC1

r1

Taea6opo11

OH

I

3. CMHTe3bl Ha ocHoee MOC

3.3. nony'4eHMe Kap60HM/1bHblX COeAMHeHMH								X= NMe2. Cl, OR,
							0			OM
								rx	x	-/..
						R'				R R'
				(R-MJ				R._lzN-OMe
0			OMe
	R--<		R-<
	H(±)		OMe

Br

1. Bu-Li/THF/-78°C

I

I /4

HO OH

I

...

Br

N/4

2HN=

<->

N

Br

TsOH/A

0

N/4

Br

e

0

LJ

H

3.

°

C

1.

Bu-Li/THF/-78

I

0

.....

/4

e

0 O

.. A1<p111BaCTi-1H

2. Me2Nyo

LJ

N

H

3. H H

1

3. CMHTe3bl Ha OCHOBe MOC

	3.3. no11y eHMe Kap6oHM/lbHblX COeAMHeHM.jtF.)....._._			NI oc
0		1. CDI/THF	----l►• F
Boc-N		_ __Boc-N
	OH 2. NH(OMe)Me		2. H@	0	2.t-BuOK
			F		3. TFA
		NH			N
		Br		I	N
			o____..F		0

3.4. no11y eH111e cn111proe
			,.r-OH
	D	I	-') n
n=2	ti	R-t
	n=1	1°(+2-3C)		-
(Cat/ Et2o BF3)			O
			)		OR'
			R'

1. R-M

◄

2.H ©

1

	0						OM
EJR-M	}-H			H--1					R-(
	1.R'_.-)i			/ 2.H			©
	H		O	R			H			OH
			Ji
										R'
		. R'	0
					©
			/ 2.H				OH
				R R"						°
										3
							R'

OH

R_/1°(+1C)

3. CMHTe3bl Ha ocHoee MOC

3.4. nony'feHHe cnHpToe
Br			MgBr	0
						HO
				1.
...			....,..1....		MeO
Mg/THF

Meo

EtO 0

1. 2PhM9Br/Et20

2 H@	HN
3. H2/Pt02

2 H@

Cl

0

	HO
Ph	Ph
	0Hc1--		_..HO
			Ph		N
A3al..lVIKJ10HOn				Ph
	Ph	HCI		Ph	Im
				Cl
	OH

NEt3

Cl

HBr

...

AcOH

Br

HO

TepcpeHaAI-IH

Ph

N

I'-:::

Cl

Knorp11Ma3on

3. CHHTe3bl Ha OCHOBe MOC

3.5. nonyl.4eH111e 3MIIIHOB

@ e

@

NH2

0

4

• 3aMew,eH111e MeTanna Ha a3MAorpynny

R-M Ts-N-N=N

R-N=N=N

(NaBH )

R-

30-80%

[H] _,

s-Bu-Li

0

Me2N 0

@ 0

7'.......,,,Li Ts-N=N-N

THF/-78°C

82%

• BoccTaHoeneH111e npoMe>t<yrO'fHblX HMHHOB (aAAYTbl MOC 111 HHTp111noe)

►

[HJ

N H

R' =N

M

2

R-M -----1

N

[ R)l_R'I

(NaBH

RAR'

CN

Br' 'V "Br

Cl

..

Cl

NMgBr

Cl--<I/ r---1

/'-./'-.

i-BuMgBr

NaH/DMF

..

..

Cl

Cl

0

hch

ekotikhin

C116yrpaM11H

3. CHHTe3bl Ha OCHOBe MOC

	3.5. nony\feHMe aMMHOB				R"'
					N,..
	• npHCOeAHHeHHe MOC K HMHHaM				1. II
					R" R'
				R-M
					2.H ©
	Ph-{o	NH2Et	N	Et	HN-Et
		---	Ph\//	- 1.Bn-MgCI	Ph-<
	H	DCM/MgS04	H	2.H ©	Bn
		-H20

• BBeAeHHe B HMHH OCT3TKa XHpa/lbHOro aMHHa n0380/lffeT npHCOeAHHffTb MOC

AHacrepeocTepeoceneKTHBHO

0		1.LiAIH4			0	H		..
				I
	OH			OTMS			I
NH2		2. TMS-CI/NEt3	NH2	DCM/MgS04			0	OTMS

1.Meli

2.H ©

	HN
I '>---'-
o	\

	Nal04
HO	•
	MeOH