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

CHO

•

HO

OH

OHCOCOCH3

P= PhCH2 ; P ′ = t-BuMe2 Si

OP

CHO

OP

P = t-BuMe2Si

O

OH

P ′O

OP

(OEt)2

P O O

O

(EtO)2 P

P(OEt)2

O

O	OH
P	HO
	(EtO)2

•

165d

O

OH

P ′O

OP

165e

OCOCH3

O

PO

OP

83f

OP

OP	‘a molecular wire’

419

TABLE 18. Intramolecular HWE reactions for macrocyclizations

Substrate

Product

Reference

O

O

O

(MeO)2 P

CHO

O

O

166a

O

O

(OMe)2

CHO

P

O

O

O

166a

O

O

O

O

( )3

OP

MeO

OP

MeO

O

O

OP

OP

O

O

O

O

O

O

O

O

O

O

O

O

PO

COOMe

PO

COOMe

O

166b

CHO

O P

O

P = t-BuMe2 Si

(OMe)2

O

O

OMe

OP

O

O

OMe

OP

H3 C

O

OP

O

COOMe

H3 C O

OP

O

COOMe

CHO O

CH2

166c

P

O

O

(OMe)2

P = t-BuMe2	Si	Pimarolide methylester

420

TABLE 19.		Dienes and polyenes through the Wittig		Horner reaction
	Substrate	Phosphine oxide			Product	Reference

CHO

			O
			Ph2 P
	OP
PO	O		PPh2
	CHO
	P = t-BuPh2 Si		O
	SiMe3	HO	PPh2
	CHO		O

OPPh2

R3

O

R1

R2

OP

PO O

SiMe3

HO

R3

R1 R2

171a

171b

171c

171d

continued overleaf

421

422

TABLE 19.		(continued)
Substrate			Phosphine oxide	Product	Reference
OHC	O	OMe		O OMe
			CH3		171e
		O	PPh2	O
	O		O	O
				H O	O
OHC		N	O	O
		O
			PPh2
		OMe		HO
				O	171f
				O
			O	N
				O
				MeO
				Rhizoxin

9. Synthesis of conjugated dienes and polyenes

423

E. Iterative Wittig-type Reactions

When the HWE reaction is performed with anylide having a functional group such as an ester or a masked aldehyde on the terminal carbon, the olefin generated can be set to perform another HWE reaction in an iterative fashion by generating the aldehyde group through simple chemical manipulations. This methodology is very popular for polyene synthesis. Various functionalized ylides for specific homologation of carbonyl compounds are available. For example, triethylphosphonoacetate is a two-carbon homologating agent. The ylide generated from this reagent reacts with aldehydes readily to give an ˛,ˇ- unsaturated ester, which on reduction and controlled oxidation sequence generates ˛,ˇ- unsaturated aldehyde which is ready for the HWE reaction again (equation 99)172. Similarly, a dienic ylide has been introduced for six-carbon homologation (equation 100)173. Polyenes having up to seven-conjugated double bonds have been prepared utilizing this iterative protocol173c. Fourand five-carbon bifunctional HWE ylides having an imine functionality have also been developed174,175. These synthons react with aldehydes and ketones in the presence of base, in Wittig fashion, and on work-up release aldehyde group (equation 101)175. The iterative HWE protocol has been used for the synthesis of the polyene portion of cyclophane-based trienic esters176 and the natural product, roxaticin177.

CHO	1. (EtO)2 P(O)CH2 COOEt, NaH			CHO
	2. DIBA H
	3. MnO2
	1. repeat steps
		1 − 3 +	−	(99)
	2. Ph3 P(CH2 )7COOH Br
		n-BuLi
	3. I2

(CH2 )6 COOH

O

O

CHO

2.DIBA H			(100)
3. MnO2	1. Ph3P	COOMe

4.Cat I2

5.repeat steps 1− 4

O

O

COOMe

424	Goverdhan Mehta and H. Surya Prakash Rao

CHO

Cl

1. NaHMDS	O
2. SiO2	P	C6 H11	(101)
3. repeat 1 and 2	(EtO)2	N

CHO

Cl

F. Peterson and Related Reactions

The Peterson olefination reaction involves the addition of an ˛-silyl substituted anion to an aldehyde or a ketone followed by the elimination of silylcarbinol either under acidic (anti-elimination) or basic (syn-elimination) conditions to furnish olefins178. Thus, Peterson olefination, just like Wittig and related reactions, is a method for regioselective conversion of a carbonyl compound to an olefin. Dienes and polyenes can be generated when the Peterson reaction is conducted using either an ˛,ˇ-unsaturated carbonyl compound or unsaturated silyl derivatives as reaction partners (Table 20)179.

Several strategies closely related to the Peterson synthesis have been developed for diene and polyene generation. Angell, Parsons and coworkers reported a mild method for the diene installation on a carbonyl group using a -bromoallylsilane reagent in the presence of excess chromous chloride and a catalytic amount of nickel(II) chloride (equation 102)180.

R CHO + Br

Si

1. CrCl2 , NiCl2	R	(102)
2. HCl (aq.)

Bellassoued and Majidi introduced a two-carbon homologation reagent, ˛,˛-bis(trime- thylsilyl)-N-tert-butylacetaldimine, the anion of which reacts with an aldehyde in the presence of a catalytic amount of zinc bromide to afford two-carbon homologated ˛,ˇ- unsaturated aldehyde (equation 103)181. This sequence in an iterative mode provides access to polyenes. A four-carbon homologation reagent has also been introduced by the same group182. Anion generated from trimethylsilylcrotanaldimine reacts with aldehydes smoothly in the presence of a catalytic amount of caesium fluoride to furnish a dienal (equation 104)182. Wang and coworkers have described the synthetic utility of - trimethylsilyl substituted allyl boranes for stereospecific generation of terminal 1,3-dienes (equation 105)183. Ring opening of epoxysilanes with alkenyl cuprate reagents in the presence of BF3 Ð Et2O affords ˇ-hydroxysilanes which, on Peterson elimination, give stereospecific dienes183.

TABLE 20. Dienes and polyenes through the Peterson reaction

Substrate	Silane	Product	Reference
CHO			Si(CH3 )3
(CH3 )3 Si	Si(CH3 )3		179a
		(CH3 )3 Si

O		(CH3 )3 Si
			Si(CH3 )3
Ph			Ph
S		(CH3 )3 Si	S
	CHO
Ph			Ph
Ph		Ph
O		O
Ph	CHO	Ph	(CH3 )3 Si

Si(CH3 )3			179b
	(CH3 )3 Si
	Ph
	Ph
	S
	S		179c
	Ph
	Ph
	Ph
	O
		Ph	179d
	Ph
		O
		Ph

OP	(CH3 )3 SiCH2 CN	OP
OP		OP
O		179e
CH3		NC
P = t-BuMe2 Si		Calyculin fragment

425

426	Goverdhan Mehta and H. Surya Prakash Rao
	CHO		(H3 C)3 Si
		+	NC(CH3 )3
			Si(CH3 )3
			1. ZnBr2
			2. H3O+	(103)

CHO

CHO

+ Me3 Si

NC(CH3 )3

1. CsF, DMSO

2. ZnCl2 , H2 O

(104)

CHO

(H3C)3Si	B	1. RCHO
		R

2. NaOEt/NaOH (syn elimination) or

H2SO4 (anti elimination)

(105)

G. Organotitanium Reagents

Tebbe’s reagent, Cp2TiCH2Al(CH3)2Cl, converts carbonyl compounds to methylenes184. This reagent when applied to ˛,ˇ-unsturated aldehydes and ketones generates dienes (equation 106)184c. Synthetic utility of the reagent for generation of dienes and polyenes is limited because of the difficulty in the preparation and incompatibility with other functional groups such as esters etc.

OP

OP

O

Cp2TiCH2 Al(CH3)2 Cl

(106)

THF, Pyridine

P = t-BuMe2 Si

9. Synthesis of conjugated dienes and polyenes

427

Titanacyclobutenes, prepared readily from Tebbe reagent and alkynes, react with aldehydes and ketones to form insertion products which undergo facile retro-Diels-Alder reaction to afford substituted 1,3-dienes (equation 107)185.

Cp2Ti	+ R		CHO						Cp2Ti		O
				Cp2Ti
					R		(107)
				O

+ R

Organotitanium reagent generated from 1-tert-butylthio-3-trimethylsilyl-1-propene condenses with aldehydes to give 1-tert-butylthio-(E, Z)-1,3-alkadienes, via ˇ-hydroxysilane intermediates186. The tert-butyl sulphide group on the diene can be replaced by an alkyl group by a cross-coupling reaction with a Grignard reagent in the presence of nickel catalyst (equation 108). The utility of this method was illustrated by an application to the synthesis of spilanthol, a naturally occurring insecticide186.

S

1. t-BuLi

S

SiMe3

Ti(OPr-i)4

2.CHO

Ni(dppp)Cl2 MeMgI

(108)

VI. COUPLING REACTIONS

A. General Aspects

Though coupling reactions are among one of the earliest known C C bond forming reactions, they have found only limited synthetic applications owing to lack of control and unsatisfactory yield. However, during the past two decades development in organometallic chemistry had a profound impact on revising the coupling process as an important synthetic reaction. Employing a variety of organometallic catalysts and intermediates it is now possible to carry out diverse coupling reactions in good yield, under mild conditions and with high stereocontrol.

428	Goverdhan Mehta and H. Surya Prakash Rao

B. Reductive Carbonyl Coupling Reactions

1. The McMurry coupling reaction

The McMurry reaction involving low-valent titanium species accomplishes coupling of

two carbonyl groups to furnish alkenes187. The low-valent titanium species is generated either from TiCl3/LAH187a, TiCl3/Mg188 or TiCl4/Zn Cu189. When one or both carbonyl substrates carry one or more additional double bonds, dienes or polyenes result from this reaction (equation 109)187a. The McMurry coupling reaction is remarkably selective and a wide variety of functionalities are tolerated. This reaction can be carried out in both interand intramolecular modes to furnish a variety of dienes and polyenes. Synthesis of dienes and polyenes where McMurry coupling has been a key reaction is given in Table 21190.

CHO

Zn−Cu TiCl3	/ LA H
	(109)

	β - carotene
TABLE 21. Dienes and polyenes through McMurry coupling
Substrate	Product	Reference

CHO

CHO

	190a
	Fusicoccane type
O	190b

A minicarotene