Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of dienes and polyenes. V. 1 / 0359 480

9. Synthesis of conjugated dienes and polyenes

439

Cl

Cl

2.	OH	1.			C5H11,Pd(PPh3 )4 −CuI

,

PdCl2 (PhCN)2 −CuI

(136)

OH

C5H11

2.Stille coupling

a. Alkene alkene coupling. The cross-coupling reaction of alkenyltin reagents with alkenyl electrophiles catalysed by palladium complexes to generate dienes of high stere-

oselectivity is known as Stille coupling (equation 137)235. When leaving group on the alkenyl electrophile is iodide (or iodonium salt)236, triflate or a mesylate237, the reaction works at room temperature, whereas with vinyl bromides, heating up to 100 °C is required. Vinylstannanes can be prepared by a variety of methods such as transmetallation

of vinyllithium238, vinylaluminium239, vinylcuprate240a or reaction of vinyl halides with a tin cuprate240b. They can also be prepared by the stereospecific addition of a tin metal

bond across a carbon carbon triple bond241,242. Palladium catalysts such as Pd(PPh3)4, PdCl2(MeCN)2, PdCl2(PPh3)2 and Pd2(dba)3 are commonly employed. However, the presence of a palladium catalyst for this coupling is not always necessary. Piers and

TABLE 24. Enynes through alkyne alkene coupling

A lkene component	A lkyne component		Enediyne/dieneyne/eneyne	Reference
	SiPh2 (Bu-t)	(EtO)2 HC	SiPh2 (Bu-t)
Cl	CH(OEt)2			234a
R			R
				234b
	O
OTf		O
			Me3 SiCH2
	CH2 OP			CH2 OP
CH2 SiMe3				234c
I	P = THP
	I		(CH2 )7COOBn
	(CH2 )7COOBn			233
		OH
OH

440	Goverdhan Mehta and H. Surya Prakash Rao

Wong reported that stoichiometric amounts of copper(I) chloride alone can promote the intramolecular Stille coupling (equation 138)243. In fact, copper(I)-mediated reaction was cleaner and faster compared with that catalysed by Pd(0) species. Selected examples of intermolecular Stille coupling reactions leading to dienes (Table 25)236a,242b,244, polyenes (Table 26)245 and macrocyclizations (Table 27)246 are given in the respective tables.

SnBu3

I

+

(MeCN)2 PdCl2

(137)

I

COOMe

COOMe

(138)

Cu(I)Cl

Me3 Sn

trans-1,2-Bis(tri-n-butylstannyl)ethylene, prepared from trans-dichloroethylene in a two-step process via tri-n-butylchloroethenylstannane247, is a versatile substrate for double Stille coupling in a sequential manner. Barrett employed it to generate the required dienyl stannane in the first step and later employed it for further coupling with another alkenyl iodide during the synthesis of tetraene portion of calyculin A (equation 139)248. Extraordinary versatility of Stille coupling was demonstrated by Nicolaou and coworkers during the total synthesis of rapamycin. A double Stille coupling was employed for the macrocycle construction and the formation of a triene unit in the total synthesis of this polyene macrolide antibiotic (equation 140)249.

I	1. Bu3Sn
	SnBu3
NC	PdCl2 (PPh3)2

Me

2. I

PdCl2(PPh3)2

CN

(139)

(C1 − C14 −Tetraene nitrile unit of calyculin A)

TABLE 25. Synthesis of dienes through a Stille coupling reaction

Stannane		Vinyl halide/triflate		Product	Reference
OP		O	OP	O
	Br	COOMe		COOMe
SnBu3
					244a
	P = THP
				(benzoleukotriene B3 )
Bu3Sn	COOMe	OTf		COOMe	244b
			O
	O
	I		(C16	Juvenile hormone)
	SnMe3	OH		OH	236a
SnBu3		OTf
CO2Et	Me	CO2Bn	EtO2C		244c

CO2Bn

continued overleaf

441

442

TABLE 25. (continued)

Stannane	Vinylhalide/triflate		Product	Reference
Ph	Br	:	O
	:
SnBu3		Ph	S	244d
	S		Tol-p
	O
	p-Tol
		SnBu3
Bu3Sn	OTf			242b

	SnBu3	Bu
		Bu
		TfO

244e

Bu3Sn

TABLE 26. Synthesis of polyenes through Stille coupling

	Stannane		Alkenyl iodide
	O O		S
	O	OMe	S
			I
			SnBu3
			CN
			I
			SnBu3

Me3 Sn

SnMe3 I

Product		Reference
O O	S
O OMe	S	245a

(rapamycin fragment)

CN

245b

(calyculin A fragment)

245c

443

444	Goverdhan Mehta and H. Surya Prakash Rao
TABLE 27. Intramolecular cyclizations through Stille coupling
Substrate				Product		Reference
	O	OTf		(CH2 )7
Bu3 Sn						246a
	O (CH2 )8
			O	O
Tf	Tf			Tf	Tf
N	N			N	N
H		H	H		H	246b
H	H			H	H
Bu3 Sn	I

Papuamine

	OP		OP
Bu3 Sn	OP′			OP′
				H
	Br
		O	N	N
	HN			O
	N		S
	S
		P = t-BuMe2 Si;P′ = MeOCH2
	Me3 Sn			COOMe
OTf
	COOMe
COOMe
			MeOOC
O	SnMe3		O
O	OTf		O

246c

246d

246e

9. Synthesis of conjugated dienes and polyenes

445

I

SnBu3

I

Bu3 Sn Me

OH

O

O

H

(140)

OMe O N

H

O O

H

OMe

O OH

O

OH

OMe

Rapamycin

b. Alkene alkyne coupling. Alkynyl tin compounds couple with vinyl iodides or vinyl bromides under palladium catalysis to result in conjugated enynes stereospecifically250. This reaction has been employed for the enyne formation leading to the synthesis of a tetrahydropyranyl derivative of a natural insecticide, (3E,5E)-8-(2-thienyl)-3,5-octadien- 7-yn-1-ol (equation 141)250. An intramolecular version of this reaction generates a 10membered ring analogue of the chromophore of the antitumer antibiotic neocarzinostatin (equation 142)251.

OP

SnMe3 +

S

I

(MeCN)2PdCl2 (141)

OP

P = THP

S

446	Goverdhan Mehta and H. Surya Prakash Rao
	SnBu3
Br	Pd(PPh3 )4	(142)
HO	HO
	OSiEt3	OSiEt3

Bromoalkynes also couple with vinylstannanes readily to result in enynes. Synthesis of protected enynals via cross-coupling of vinylstannanes with 1-bromoalkynes in the presence of a catalytic amount of Pd(II) has been reported (equation 143)252. Hiyama and coworkers extended the Stille methodology for sequential three-component coupling of trimethylstannyl(trimethylsilyl)acetylene with a vinyl iodide in the first step and cross-coupling of the intermediate trimethylsilylethyne with another alkenyl iodide in the presence of tris(diethylamino)sulphonium trimethyldifluorosilicate in the second step to generate a dienyne (equation 144)253. Both steps occur under palladium catalysis, in one-pot, to result in stereodefined 1,5-dien-3-ynes.

	OEt	PdCl2 (MeCN)2	OEt
Bu3Sn	+ Br
		hydroquinone
	OEt		OEt

(143)

1. Pd(PPh3 )4

Me3Sn

SiMe3

C4 H9

C4 H9

2. (Et

N) S

+ Me

SiF

−

C6 H13

I

2

3

3

2

I

C6 H13

(144)

3. Suzuki coupling and related reactions

Coupling of 1-alkenyldiorganoboranes, prepared readily by hydroboration of terminal alkynes, with bromoor iodo-alkenes in the presence of a catalytic amount of palladium(0) complex and a base, is known as Suzuki coupling (equation 145)254. Stereoselectivity in this reaction is very high and the yields are good. Stereochemistry of both the coupling partners, viz. organoborane and vinyl halide, are retained in the reaction. Since, both E 255 and Z-vinylboranes256 can be prepared stereoselectively from 1-alkynes, this coupling reaction is of immense synthetic value (Table 28)257. Vinylboranes can be prepared by syn addition of either catecholborane or disiamylborane across terminal alkynes. The presence of an equivalent of a base such as TlOH, Ag2O or even Na2CO3 is a must for this reaction, since the base assists in the formation of organoborates, thereby increasing the acidity of the ˛-carbon atom254a,258.

+ Br	Pd(PPh3 )4
O	NaOEt

B O

(145)

9. Synthesis of conjugated dienes and polyenes

447

Stereoand regioselective synthesis of trienes and tetraenes has been reported by palladium-catalysed coupling of (E)- or (Z)-1-alkenyl boronates with (E)- or (Z)-2-bromo- 1-phenylthio-1-alkenes followed by treatment with a Grignard reagent in the presence of a nickel catalyst (equation 146)259.

O

B

Br +

O

PhS

1. Pd(PPh3 )4 , NaOH

	2. Me2C		CHMgBr	(146)
	NiCl2 (dppp)

Stewart and Whiting have reported a useful application of sequential Heck and Suzuki coupling reactions of a vinylborane pinacol ester with palladium catalysis to generate a tetraene (equation 147)260.

C5H11			O
		+	B
			O
	I
	PPh3 , TlOA c, Et3N		Pd(OA c)2

O

B	(147)

O

C5H11-n

Heck product

I

Pd(OA c)2

C5H11-n PPh3 , KOBu-t

C5H11-n

n-C5H11

Suzuki product

TABLE 28. Dienes and polyenes through Suzuki coupling

Substrate		Alkenyl halide	Product	Reference
H	B(OH)2		HO(CH2 )9	257a
HO(CH2 )9	H	Br

	Bombykol
O
B
O	Br
	257b
	Allofarnesene

O O O

O

I

B

OP

2

P = PhCH2

OP

COOMe

I

R

B OP

2

P = TBDMS

O O O

O

OP

257c

Tris porol B

OP

COOMe

257d

R

OP

448