The Diels-Alder Reaction

M

M

M

M

+	200 C	! "
	20%

M

M

M

O	O
	H
PhH, 35 C	! "
+
quantitative
O	H
	O

M

M

M

M

	E	E	R	E
	PhMe, Rfx, 48 h, 73−75%			E
R	E	E	R	E
	PhMe, Rfx, 48 h, 70−88%			E
	1	E
			R	E
	E
	PhMe, Rfx, 48 h, 73−77%			E
	R = CH2CH(OAc)Ph, CH2CH(OAc)CH2CH2Ph		E = CO2Me

Z

R

OR1

2PhH, Rfx, 48 h 70−92%

Z		Z
R	+ R	+	R	+ R
			Z	Z
OR1	OR1		OR1	OR1

Z = COMe, CO2Me, CONM2

R = i-Pr, n-C6H13, Ph, p-BrC6H4, p-MeOC6H4

R1 = H, Me, STM, TBDMS

#

M

M
	OR						OR
	R1	NO2	MeOH		THF, r.t.		NO2
N	+		−80 C to r.t.		aq. AcOH-AcONa		R1
	R2				pH 4.6	O	R2
	O					overall yield: 32−76%! "
	3

R = Me, OMOM, TBDMS; R1 = H, Me;

R2 = H, Me, CH2OBn, i-Pr, Ph, 2-Fu, 3-Fu, o-Cl-C6H4, p-OMe-C6H4, p-NO2-C6H4; R1-R2 = −(CH2)4−

		TBSO		O
				N Ph
				O
O			O
	O		N Ph
			O	O
	O	1. −70 C, 96%
		2. SiO2, 83%
	O
	O
	1. 80 C, 17 h		TBSO
	2. HF
	76%
TBSO				4 NMe2
	O
	80	C, 25 h,	E
O	66%
			1. 20 C, 92%
			2. HF	O
	O	O
		+
		E	E

E = CO2Me

H

O

Me

1.110 C, 48 h

2.HF

60%

1. E E

O

2.LiAlH4/HF 85%

E

1.

E

2. LiAlH4/HF

OH

OH

OH OH

M

M M

M

TBSO

R

R

TBSO

R2

O

R2

R3

2

3

PhMe, 20

C

R

3

+

1. LiAlH4

R1

OH

CO2R

24−72 h

2. HF 10%

Ph N

R1

N

CO2R

R1

Ph

Ph

Ph

overall yield:

5

64−82%

R = Me, Et, t-Bu; R1 = H, Et; R2, R3 = Ph, CO2Me, CO2Et

	R	CO2Me	CHCl3, Rfx		R	CO2Me
	R1	+			R1
	N		20 h, 50−79%		N	CO2Me
		CO2Me
	R1				R1
	6					! "

R = H, CH2NMe2; R1 = Me, Et

M

M

		TMSO				TMSO
			R			8
			7						OSMT
					R1	R2
		R = Ph, 2-Fu, 2-Th, p-PhC6H4
		1. PhMe, 100 C, 27 h					1. PhMe, 100 C, 24 h
		2. DDQ, AcOH-PhMe,					2. DDQ, Rfx, 8−20 h
		Rfx, 20 h					35−64%
		19−85%					HO		R1 R2
	OH
R		R2					R2 R1		OH
	R1		R1, R2 = H, CN, CO2Me
					O
					Cl		OMe
					Cl	Cl
						OMe
					CCl4, r.t., MeO
					2 d, 53%		OSMT
					Cl	Cl
			OSMT				OSMT
					Cl	Cl
				9			OAc
			OMe				OMe	O
		O		, r.t.,			CCl4, r.t.,
			CCl						OH
			4				4 d, 40%
			4 d, 56%
	Cl						Cl
		Cl	Cl				Cl		Cl

M

		M
F
OSiPh3	CF3	R2
F
		R
		F
	OSMT	R1
10	11	12

R, R1, R2 = H, Me, OMe, OSMT

M

M

M

					O
							OH
					O
	F	1. PhH, 110			C, 20 h, 45%	HO
Ph3SiO		2. SiO
	F		2			F	OH
							OH		O
	10	1. PhH, 90 C, 10 h, 69%
								+
		2. SiO2		O					O
						HO		Ph3SiO
						F	OH	F	F

O

M

E

E

F3C

E

100 C, 18 h, 63%

E

F3C

E = CO2Me

OSMT

CF3

H

CO2Et/I2

11

100

C, 72 h, 28%

CO2Et

O

O

O

H

+

PhMe, 25 C, 15 h

65%

F

H

F

! "

F

HCl, 91%

OSMT

O

TMSO

O

O

12

R

O O

R O

O

R1

Ot-Bu

PhH, ∆, 3.5-5 h

R1

Ot-Bu

+

O

57−100%

O

R2

R2

R3NH2,

R

DCM,

OH

42−72%

R1

DDQ −H2O

CO2t-Bu

R2

N

42−90%

R3

R, R1, R2 = H, Me, CH2CO2Et; R3 = n-Bu, Bn

M

M

M

M

M

						TMSO
						R
	R	R1		R	R1	R1		14
		THF
C			C			13	C60
	60			60		PhMe, 50−110 C		C60
		O HCl						PhH, Rfx,
						OSMT 0.5−24 h, 29−48% 15		14 h, 54%

R = R1 = H, Me, OMe, Ph

M

M

M

SnBu3		DCM, r.t.	B	t-Bu	BBN
+	Br-9-BBN
		5 min		DCM, r.t., 20 h
					t-Bu
16	17
					! "
			18	OH
					H2O2
				t-Bu	NaOH
				82% overall yield

M

O

B

SnBu3

O

neat, 25 C

O

O

+

Br B

3 d, 70%

B

Bu3Sn

O

O

19

! "

t-Bu

OH

H2O2

t-Bu

OH

NaOH

Et

N, 100 C, 1h

3

70% yield

R2

SnBu3

BBr2 hexane, 25

HO

BBr3, hexane

C Et3N, NaOH

R1

( )n

0−25

( )n

( )n

C, 15 min

R

2

H

O

2

R

2

n = 1, 2

R1

H

41−80%

R

H2C

R, R1, R2 = H, Me, Ph, t-Bu,

M

M

M

	OBz			OBz			OBz
			H			H
+	O	DCM, 150−250 C		O	+		O
	R1	2-6 d, 76−92%		R1			R1
BzO	R			R			R	! "
			BzO			BzO
21	O			O			O
	20

R = R1 = H, OMe, OBz

	MeO2C	OEt		PhO2S	SiMe3
		( )n			23
		24
	45−80 C, 24 h			MeOH or PhH, 0−60 C
		21, n = 1 2−8 h, 96−100%
( )n		22, n = 2			( )n
	OEt					SiMe3
CO2Me						SO2Ph
	THF, HCl					LiAlH4
	3 h					THF, 92−94%
( )n						F , THF
	O 43−65% overall yield					7−8 h, 76−100%
	CO2Me				( )n

( )n

O

M