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

CHO

O

O

154d

PPh3

	O O		O O
	OCH3		Cl
		CH3	H3CO
H3CO	C l
	H3CO	N
		COOCH3

	OP
OHC	OCH3
	OCH3
		PPh3
	OCH3

P = t-BuMe2 Si

OBz

	OBz	Ph3 P
OHC		COOMe

CH3

N

COOCH3	OCH3
H3CO OCH3	OCH3
	154e
OP	CH3
OCH3

Maytansinoids

COOMe

154f

eicosinoid monohydroxy fatty acid

409

410

TABLE 14. Polyene synthesis through the Wittig reaction

Ketone

Wittig ylide

Olefinic compound

Reference

O

O

O O

	O O
OHC	COOEt
	p = t-BuPh2Si

HO

		CH3
	H3C	O OH
	O	CHO
	H3 C

MeO H O H

R

CHO

O O

R = NHCOOCH2 CCl3 ; P = PhCH2

Ph3P	C5H11
	PO

OMe

Ph3P	O
O
	CH3
O	N
Ph3P
O	OP

COOEt

155a

OP

Lipoxin A

HO

	CH3
H3 C	O	OH				155b
					O O
O
H3 C
	Neocitroviridinol				OMe
						CH3
		MeO			O	N
			H	O	H	155c
R
			O		O	OP
					O

H3 COOC	O	CHO	Ph3 P		H3 COOC	O
						155d
OHC	COOMe		S		S
			S	PA r3	S	COOMe

OCOPh	OCOPh	155e
	A r = p-Anisyl
	PPh3
	CHO
		155f

411

412	Goverdhan Mehta and H. Surya Prakash Rao

B. Arsenic Ylides

Stabilized arsenic ylides are more reactive than the corresponding phosphorus (Wittig) ylides159. In many cases where phosphorus ylides failed to react with carbonyl compounds, the corresponding arsenic ylides have been applied in the olefin forming reactions. Huang and coworkers developed the chemistry of arsenic ylides for the synthesis of dienes and polyenes160. Thus, 3-ethoxycarbonylallylidenetriphenylarsone reacts with a variety of aldehydes and ketones to afford diene esters (equation 95). This reagent reacts with aromatic aldehydes stereospecifically leading to the formation of E, E-products. Another reagent of high synthetic potential is formylallyltriphenylarsonium bromide161. This reagent reacts with aldehydes to give dienals, which can again be subjected to olefination in an iterative fashion (equation 96). In a similar manner, an isoprenoid arsone reagent, 3-methoxycarbonyl-2-methyl-2-propenylidenetriphenylarsorane, for appending isoprenoid

unit to aldehydes, has been developed (equation 97)161b. Applications of arsenic ylides for the synthesis of dienes and polyenes are given in Table 15160,161a,162.

	CHO
	+	(C6 H5)3 As	CH CH CH COOEt
			NaOEt	(95)
			COOEt
CHO	Br−			CHO
+	Ph3 As+	CHO	1. K2CO3
			2. I2
N			N

(96)

CHO

+Br−+

N	Ph3 As		COOMe
		NaOMe	(97)

COOMe

N

C. The Horner Wadsworth Emmons (HWE) Reaction

An important modification to the Wittig reaction is the use of stabilized phosphonate carbanions in olefin synthesis. This reaction, originally discovered by Horner but developed by Wadsworth and Emmons, is used extensively for transformation of a carbonyl

TABLE 15. Dienes and polyenes with arsenic ylides

Substrate	Arsenic ylide			Product	Reference
	CHO				COOEt
	Ph3A s	COOEt			160
					O
	CHO
	Ph3A s				161a
N		O	N	Navenone
	O
CH3 (CH2 )8	Ph3A s	N	CH3 (CH2 )8		O

CHO	N	162 a
	Achillea amide

continued overleaf

413

414

	TABLE 15.	(continued)
	Substrate		Arsenium ylide		Product		Reference
	S			O	S		162a
		CHO	Ph3A s	N
						O
						N
					Otanthus maritina amide
						O
		O				COOMe
	OHC			C5H11			162b
		COOMe	Ph3A s		H	H
		H H
					Leukotriene A 4 (LTA 4) methyl ester
	PhCH2O	CHO			PhCH2O	CHO
	H		Ph3A s	CHO	H		162c
		OCH2 Ph				OCH2Ph

9. Synthesis of conjugated dienes and polyenes

415

group to an olefin163. Phosphonate carbanions are more nucleophilic than the corresponding Wittig ylides, and therefore are more reactive towards carbonyl compounds, especially when the substituent on the phosphonate reagent is an electron-withdrawing group. When the substituent on the phosphonate reagent is an electron-withdrawing group such as an ester or ketone, the product in the olefination reaction is predominantly E.

HWE reaction has been used extensively for the synthesis of dienes and polyenes. Examples from recent literature are shown in Table 16 (dienes) and Table 17 (polyenes). HWE reaction also has been used for intramolecular cyclizations leading to polyene macrolides (Table 18).

D. The Wittig Horner Reaction

Another variation of the Wittig reaction is the Wittig Horner reaction, in which the anion generated ˛- to phosphine oxide is used as a nucleophile to react with carbonyl compounds167. The intermediate formed in this reaction, ˇ-hydroxyphosphine oxide, is isolable particularly when bases with lithium counterion are used for deprotonation. Since the ˇ-hydroxyphosphine oxides are diastereomers, they can be separated and subjected to elimination to form the corresponding alkenes168. Since the elimination of phosphonate moiety is syn, stereospecific alkenes are obtained from the elimination step169. As expected, the generation of erythro and threo isomers is dependent on the solvent and the reaction conditions.

When one of the reacting partners in the Wittig Horner reaction, either the phosphine oxide or the carbonyl compound, has a double bond, the product is a diene. The Wittig Horner reaction was utilized by Smith and coworkers in the total synthesis of milbemycin (equation 98)170. They found that when sodium hexamethyldisilazide was employed as a base, the desired E-diene selectivity is high (85%). Some examples from the literature where the Wittig Horner reaction has been utilized for the construction of E-double bonds present in dienes and polyenes are given in Table 19171.

	H	O
		Ph2 P
	O
	O
	+	COOMe
	CHO
	OP
	H	NaN(SiMe3 )2
	O
	O	OMe
		(98)
	OP
	COOMe

OMe	P = t-BuMe2 Si

416

TABLE 16. Diene synthesis through HWE reaction

Starting aldehyde		Phosphonate	Product	Reference
OHC	CH3	CH3 OOC	CH3
		O
	OP	(MeO)2 P CH2COOCH3	OP
				164a
	S		S
	S		S
	P = MeOCH2
			Methylmaysenine
PO	NH(BOC)	COOEt	PO	NH(BOC)
		(OEt)2 PCH2
OHC		O
	P = t-BuMe2Si			164b

EtOOC

lejimalides

O

O

O

O

CHO

R = (MeO)2 C6 H3 CH2

CH3 CHO

O CHO

O

				O	O
	O	OH
			O
	P
(OEt)2
			N R	O	O
					O	164c
		O
						N R
					OH	O
O				O
						164d
O	P	(OEt)			CH3
		2
	O			O		COOCH3
			COOCH3
(OEt)2 P						164e
				O

417

418

TABLE 17. Polyene synthesis through HWE reaction

Aldehyde			Phosphonate		Product	Reference
	CHO	O			CN
		(EtO)2 P	CN
OP				OP		165a
P = t-BuMe2Si
OP ′ OP		O		OP ′	OP
	CHO	(EtO)2 P		COOEt		COOEt
						143
P = t-BuMe2Si; P ′ = Et3Si					(Amphotericin fragment)
		O	o
Br	CHO	(EtO)2 P	o	Br	CHO	86
	CHO	O
HO		(EtO)2 P	CN	HO	CN	165b
		O
		(EtO)2 P
CHO			Ph
		MeOOC		Ph
						165c
					COOMe