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0040-4039(95)01123-4

Tetrahedron Letters, Vol. 36, No. 32, pp. 5683-5686, 1995 Elsevier Science Ltd

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Conjugate Addition of Zinc Halide Derived Trialkylsilyl(dialkyl)zineate Reagents to a,l~-Unsaturated Carbonyl Compounds

Andrew Vaughan and Robert D. Singer*

Department of Chemistry, Saint Mary's University Halifax, Nova Scotia, Canada, B3H 3C3

Abstract: Trialkylsilyl(dialkyl)zincate reagents, PhMeaSiZnR2Li, (R -- Alkyl), are easily prepared in THF solutions v/a the addition of two equivalents of methyUithium and one equivalent of dimethylphenylsilyllithium to zinc halides (ZnI 2 or ZnClz). The resulting zincate reagents undergo conjugate additions to a variety of a,p-unsaturated enone substrates. A single silylzineate species is observed by low temperature 29Si NMR of a THF solution. These reagents afford high yields of silylated products and offer a safer route to these adducts than do trialkylsilyl(dialkyl)zincate reagents prepared v/a the addition of dimethylphenylsilyllithium to extremely pyrophoric dialkylzinc reagents. This method has been extended to the conjugate addition of trialkylsilyl(diamido)zincate reagents to enone substrates.

The reaction of dimethylphenylsilyl(dialkyl)zincate reagents with a, 13-unsaturated carbonyl compounds

has been recently reported by Fleming and coworkers, t These workers prepared zincates v/a the addition of

dimethylphenylsilyUithium to a solution of either dimethyl- or diethyl-zinc at 0 °C and used them at -78 *C. It

was noted that these reagents provided higher yields of the conjugate addition products than did the

corresponding silylcuprates. This method provides a good complementary method to the use of silylcuprate

reagents for the addition of trialkylsilyl groups to a, 13-unsaturated carbonyl compounds and is even superior

to silylcuprates when being added to a,13-unsaturated esters. However, the use of the highly pyrophoric

dialkylzinc compounds in their preparation represents a severe drawback from the point of view of the synthetic

chemist requiring such a reagent but who is inexperienced and unfamiliar with the use of these very hazardous

reagents.

Inspired by earlier work of Nozaki and co-workers 2 in which trialkylzincate reagents were prepared from

the addition of three equivalents of an alkyllithium to zinc (II) chloride, we endeavoured to prepare

unsymmetrical zincates of the general formula, PhMeaSi(R)2ZnLi, using a similar method (Equation 1). We

report herein that lithium dimethylphenylsilyl(dialkyl)zincate reagents can be easily prepared via the addition

dimethylphenylsilyllithium to the dialkylzinc compound generated in situ from the addition of two equivalents

of an alkyUithium reagent to zinc (II) chloride, ZnC12, or zinc (II) iodide, ZnI 2 , in THF and THF / TMEDA

solutions. 3 Zincate reagents prepared using this method offer an advantage to those prepared previously in that

they avoid the handling of highly pyrophoric starting materials. We find that unsymmetrical lithium

dimethylphenylsilyl(dialkyl)zincates prepared by this less hazardous method selectively add their silyl moiety

to a variety of a, 0-unsaturated ketones and esters (Equation 2) to afford 3-silylated products in yields

comparable to those obtained with zincates 1"2 (or cuprates 4) prepared v/a alternate methods.

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We first investigated the effect of varying the zinc (II) halide in the preparation of the zincate. We

observed that the use of ZnCI2 gave superior yields compared m the use of ZnI2 when THF was used as a

solvent (Entries 1 - 8, Table 1). We attributed this to higher solubility of the ZnCI2 derived zincate in THF.

We next examined the effect of using a coordinating co-solvent, tetramethylethylenediamine, TME.r)A, (1.2

equivalents with respect to ZnXz) with THF. It was evident that the increased solubility of the ZnI 2 derived

zincate in THF / TMEDA solutions resulted in higher yields of the silylated products (entries 9-12, Table 1).

Interestingly, we observed that addition of TMEDA to THF solutions of the ZnCI 2 derived zinc.ate resulted in

decreased yields.

To gain some insight into the solution composition of lithium dimethylphenylsilyl(dimethyl)zincate we

obtained the ~Si NMR at -30 *C of the reagent prepared as above. Since a higher concentration of the reagent

was required (0.22M) to obtain an acceptable spectrum a THF / TMEDA (6:1 v/v) solvent mixture was used

to maintain solution homogeneity. We observed a single sharp signal at -18.4 ppm relative to a TMS reference

for the zincate prepared from ZnCI2. This indicates the presence of a single silyl zineate species in solutions

prepared using this method.

Atter having considerable success in reactions of lithium dimethylphenylsilyl(dimethyl)zincate with a,p-

unsaturated ketones and esters, we briefly explored the reactions involving lithium

dimethylphenylsilyl(diamido)zincate reagents. We prepared these zincates in a similar fashion to those prepared

earlier v/a the addition of two equivalents of lithium diethylamide to ZnI 2 to form (EtaNO2Zn in situ, followed

by the addition of dimethylphenylsilyllithium to the resulting solution at -30 *C to afford the

dimethylphenylsilyl-bis(diethylamido)zincate, PhMeaSiZn(NEtz)2Li. These reagents also selectively transferred

their silyl moiety when undergoing addition reactions with a, P-unsaturated substrates (Entry 13 and 14, Table

i). However, the chemical yields of isolated products were significantly lower than those obtained using lithium

dimethylphenylsilyl(dimethyl)zincate. We are presently investigating the use of secondary amido ligands in the

zincate reagents in anticipation that chiral secondary amido ligands will enable the asymmetric addition if

trialkylsilyl moieties m prochiral substrates.

THF or THF / TMEDA (CH3)2Zn 2CH3Li + ZnX 2(X=CI,I) -30 °C

PhMe2SiLi PhMe2Si(CH3)2ZnLi

-30 °C

(i)

5685

O PhMe2SiZn(CH3)2Li PhMe2Si O

R " ~ ' ~ R 2 THF,-78 °C ~ R"J 'X~R2

R 1= Ph, (CH2)3; R 2= CH3, Ph, OCH3

(2)

Table 1. The Reaction of % O-Unsaturated Carbonyl Compounds with ZnX 2 (X = C1, I)

Derived Trialkylsilyl(dialkyl)zincate Reagents.

Entry Substrate ZnX 2 / solvent Zincate

10

11

12

Methyl trans-cinnamate

Methyl trans-cinnamate

Methyl trans-einnamate

Chalcone

Chalcone

Chalcone

2-Cyclohexen-2-one

2-Cyclohexen-2-one

2-Cyclohexen-2-one

E-4-Phenyl-3-buten-2-one

E-4-Phenyl-3-buten-2-one

E-4-Phenyl-3-buten-2-one

13 2-Cyclohexen-2-one

14 Chalcone

ZnCh / THF

ZnI, / THF

ZnI2 / THF /

TMEDA

ZnC12 / THF

Znh / THF

ZnI2 / THF /

TMEDA

ZnC1 z / THF

Znh / THF

Zn h / THF /

TMEDA

ZnCh / THF

Znh / THF

ZnI2 / THF /

TMEDA

Znh / THF /

TMEDA

ZnI 2 / THF /

TMEDA

PhMeaSi(CH3)2ZnLi

PhMeqSi(CH3)2ZnLi

PhMeqSi(CH3)2ZnLi

PhMcaSi(CH3)2ZnLi

PhMeaSi(CH3)2ZnLi

PhMeaSi(CH3)2ZnLi

PhMeaSi(CH3)2ZnLi

PhMeqSi(CHa)2ZnLi

PhMeqSi(CH3)2ZnLi

PhMeqSi(CH3)2ZnLi

PhMeaSi(CH3)2ZnLi

PhMeqSi(CH3)2ZnLi

PhMe~Si(EhN)2ZnLi

PhMeqSi(EhN)2ZnLi

Yield s,.

(%)

96

82

82

93

77

88

78

78

95

55

64

90

4 o ~

55

• Isolated yields after flash chromatography using silica gel (hexanes/ethyl acetate 10:1).

b Yield increased to 63 % when 3 equivalents of zincate were used.

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Acknowledgements. We thank Saint Mary's University (Senate Research) for support of this research.

References and Notes.

1.

2.

.

4.

5.

R. A. N. C. Crump, I. Fleming, and C. J. Urch J. Chem Soc., Perkin Trans. 1 1994, 701.

(a) W. Tfickmantel, K. Oshima, and H. Nozaki Chem. Ber. 1986, 119, 1581.

(b) Y. Okuda, K. Wakamatsu, W. Tfickmantel, K. Oshima, and H. Nozaki Tetrahedron Lett.

1985, 26, 4629.

Typical Procedure: Preparation of Methyl 3-dimethylphenylsilyl-3-phenylpropanoate (Entry 1,

Table 1) To an oven dried round bottomed flask, equipped with a stir bar and a septum, under

inert atmosphere was added anhydrous ZnCI 2 (0.191 g, 1.4 mmol). The ZnCI 2 was dissolved in

5.0 mL of freshly distilled THF and cooled to -30 °C at which time 2 equivalents of

methyllithium (2.0 mL, 1.4 M/Et20, 2.8 mmol) were added dropwise v/a syringe. After stirring

for 15 minutes PhMeaSiLi (1.4 mL, 1.0M/THF, 1.4 mmol) was added via syringe at -30 °C and

the reaction stirred for another 15 minutes. The dark red homogeneous solution was then cooled to

-78 *C before addition of methyl trans-cinnamate (0.162 g, 1.0 mmol). The reaction was allowed

to stir for 30 minutes at -78 *C affording a yellow solution and was then quenched using a saturated

NI-I4C1 solution. After work-up and evaporation of the solvent, the crude residue obtained was purified

by silica gel chromatography (hexane/ethyl acetate 10:1) affording 0.285 g (96%) of methyl

3-dimethylphenylsilyl-3-phenylpropanoate. ~H NMR (CDCI3) 8 7.42 - 6.91 (10H, m, Ph), 3.45 (3H,

s, OCHa), 2.91 - 2.60 (3H, m, CHCH2CO~Me), 0.25 and 0.22 (6H, 2 s, Si(CH3)z); 13C NMR (CDCI3)

8 173.5, 141.7, 136.4, 134.1, 129.3, 128.1, 127.8, 127.5, 125.0, 51.5, 34.7, 32.2, -4.1, -5.5.

(a) D. J. Ager, I. Fleming, and S. K. Patel J. Chem. Soc., Perkin Trans. 1 1981, 2520 and

references cited therein.

(b) R. A. N. C. Crump, I. Fleming, J. H. M. Hill, D. Parker, N. C. Reddy, and D. Waterson

J. Chem. Soc., Perkin Trans. 1 1992, 3277.

The IR, El-MS, ~H NMR (400 MHz) and ~3C-NMR (100 MHz) spectral properties of each of the

3-dimethylphenylsilyl substituted products were consistent with those reported in the literature for the

assigned structures.

(Received in USA 25 May 1995; revised 8 June 1995; accepted 15 June 1995)