4-Oxy-substituted 1-lithio-1,2-alkadienyl carbamates: Trapping of configuratively stable allenic carbanions and stereospeific 1,4-elimination for the synthesis of alk-3-en-1-ynyl carbamates.

Tetrahedron Letters,Vol.28,No.7,pp 785-788,1987 Printed in Great Britain

4-OXY-SUBSTITUTED GURATIVELY

l-LITHIO-1,2-ALKADIENYL

STABLE ALLENIC

FOR THE SYNTHESIS

DieterHoppe

*a

CARBANIONS

CARBAMATES:

TRAPPING

AND STEREOSPECIFIC

OF ALK-3-EN-l-YNYL

and Charlotte

0040-4039/87 $3.00 + .OO Pergamon Journals Ltd.

OF CONFI=

1,4-ELIMINATION

CARBAMATES.

Gonschorrekb

a) Institut fur Organische D-2300 Kiel 1, FRG

Chemie,

Universitat

Kiel, Olshausenstr.

b) Institut fDr Organische D-3400 Gottingen, FRG

Chemie,

Universitat

Gottingen,

40,

Tammannstr.

4,

Summary: 4-Silyloxy-1,2-alkadienyl carbamates 10 on treatment with n-butyllithium form llithio derivatives 12 of moderate configurative stability. After replacement of silyloxy for the better leaving group benzoyloxy in 11, anions 15 undergo stereospecific 1,4-elimination to yield the hitherto unknown alk-3-en-I-ynyl carbamates 16 I-Lithio-I-methoxy-1,2-propadiene' 2b, are readily substitution

by deprotonation3

of 2 by electrophils

or precursors3'4 to I a much

prepared

of appropriate

leads to allenes

of enones 4. Higher substituted

lesser extend,5

and of those,

Furthermore,

oxide 2c is reported.6 tive stability7

(2a) and related a-metallated

bearing

1 with alkyllithiums.

3, which serve as synthetic

derivatives

The

equivalents

(2, R' = alkyl) have been used

in R' a potential

to our best knowledge,

of anions 2 is available.3

allenes

allenicethers,2 e.g.

leaving group,

no information

only the alk=

on the configura=

Since the N,N-diisopropylcarbamoyl

_.

group' effects

the rapid formation and stabilization of I-oxy-allyl-, n-oxy-benzyl-,' and I-oxy-propargyl IO lithiums, we investigated its possible benefits for the generation of allenic carbanions, IO,11 g including those derived from diastereomerically pure 4-oxyallenes

=1 g

RI-H,

=2 R’=CH,

1

X=H

g

X=Li

E

X

q

by -n-butyllithium

R’=H,R’=THP

&

=L R’ = LiOCH,,

R’:

THP

=8

Ti(OiPr13

In an initial experiment, smoothly

&

=3

the 2,3-butadienyl

carbamate 12'13 5 proved to be deprotonated

(ether, -78 OC, 20 min) to form the lithio carbamate

785

6, which af=

786

fords after metal-exchange excess

acetaldehyde

with chloro-tris(isopropoxy)titanium,

the a-adduct I3 8 (diastereomers15

In a similar experiment,

diastereomerically

allenel'j syn-IOa was lithiated quenched bychloro

I4 15 min, and addition

In contrary,

of

: 4) with 73% yield.

pure 7y13 4-(tert-butyldimethylsilyloxy)=

(CBuLi, ether, 20 min at -78 'C) and the reaction

trimethylsilane

syn- and anti-14.

6

(13), yielding

(70%) a 3 : 1 mixture

when the intermediate

lithium derivative

mixture

of diastereomers

was 17

12 was generated

in

situ by 1.5 equiv.

LDA in presence of 2.2 equiv. of 13 (THF, hexane, 2 h at -78 'C), dia= 7,13 pure with 70% yield. From these experiments, it -syn-14 was obtainedI

stereomerically is concluded:

1. I-lithio-allenes inversion

12 have a considerable

of the allenic

2. 1,4-elimination

stereo center

configurative

stability,

its epimerization

via

is a slow process.

of lithium silanolate

from

12 to form enynes

16 does not occur at low

temperature. Hence, carbanions

of type

highly functionalized

12 are valuable intermediates in the stereoselective 18 by electrophilic substitution.

synthes.is of

allenes

R'

R' ‘-‘3C

2

H

OCb

anti-9-11 ==

syn -9-11 ==

D R'r CHa =

L

2

R'=H

syn-

R'rH

2

R* = S'tBuMe2

g

R* = C(=O)Ph Cb : C(=OINOPrl,

R'= SiMe3

NliPrl, 12 =

onfi

+

Me3SiCI (21

i

1

7’3 H3C syn

- IL =

When the 4-0~~ group on lithiation zation

tBuMeZSiO is replaced

to intermediates

at rt, 1,4-elimination

ynyl carbamates was obtained,

y’k.

whereas

FH3

,,,, A

_SIMe

by a better

cordance

\,,,Pb

>

anti

- E

SiMe,

leaving group, e.g. in the benzoates

LDA, THF/hexane,

of syn- and anti-lla

(45

11,

1 h at -78 'C) before neutrali=

occurs to form very reactive

with 88% yield,

in the equal ratio, yield 61%. The -E/Z assignment ta.20 The down-field

l

fBuMe*S'O

of lithium benzoate

a mixture

H3c

%$3

OCb

15 (2 equiv.

16. From -syn-lla1g'7'13

- 12 =

a single stereoisomer,

3-alken-l20 (L)-16a ,

: 55) provided (f)- and (r)-16a2'

of 16a is based on the

H and 13C NMR da=

shift of 4-H, 5.82 ppm in (E)-16a versus 5.60 ppm in (Z_)-16a is in ac= 71 It is confirmed by finding the cis 5- and with the empirically calculated values.

787

3'-CH3 groups (L)-16a (8

in (E)-16a

(13.99 and 17.43 ppm) more shielded

(16.10 and 23.53 ppm). Under

: 2) furnished

assignment

(I)- and (r)-16b23

is obvious

directly

identical

conditions,

in a ratio 8

from the coupling

than the trans CH3 groups a mixture

of

of ~JJ- and anti-llb22'7

: 2, yield 48%. Here the configurative constants

in 'H NMR: (L)-16b, d3 4 = 10.8,

(E)-16b = 15.8 Hz.

onfi-11 ---w

From these results,

it becomes

clear, that the 1,4-elimination

of anions

15 proceeds

syn-stereospecifically

tive, analogous mediates,

but not an E2 reaction

I-Alkynyl decompose work-up

(TS A and B). Further, from the trapping of the -0-isobutyryl deriva= 18 to -syn-15a, by silylation , it is evident, that anions of type 15 are inter=

carbamates

have been, so far, an unknown

when kept undiluted

and LC on neutral

synthetic

applications

are

path is followed.

at rt

in the air

within

class of compounds.

gel. Further studies for exploration in progress. 18

silica

REFERENCES

The enynes

16

few hours, but they survive aqueous of

its

reactivity

and

AND FOOTNOTES

1.

S. Hoff, L. Brandsma, 609.

J. F. Arens, Rec. Trav. Chim. Pays-Bas

2.

F. Mercier,

3.

Reviews: a) R. Epsztein in E. Buncel, T. Durst (Ed.), Comprehensive Carbanion Chemistry, Part B, p. 107, Elsevier, Amsterdam 1984; b) H. F. Schuster, G. M. Coppola, Allenes in Organic Synthesis, p. 215, Wiley, New York 1984; cl P. D. Landor in S. R. Landor (Ed.), The Chemistry of the Allenes, Vol. 1, p. 155, Academic Press, London 1982; d) D. J. Pasto, Tetrahedron 40 (1984) 2805.

4.

For some more recent synthetic applications, cf: a) H. J. Reich, M. J. Kelly, J. Am. Chem. SOC. 104 (19821 1119; b) T. Jeffery-Luong, G. Linstrumelle, Synthesis 1982, 739; and ref.; cl L. E. Overman, S. W. Goldstein, J. Am. Chem. Sot. 106 (1984) 5360; d) F. J. Weiberth, S. S. Hall, J. Org. Chem. 50 (1985) 5306; e) M. A. Tius, D. P. Astrab, A. H. Fauq, J. B. Ousset, S. Trehan, J. Am. Chem. Sot. 108 (1986) 3486.

5.

Y. Leroux,

6.

M. St;ihle, M. Schlosser,

R. Epsztein,

S. Holand,

C. Roman, Tetrahedron Angew.

87 (1968) 916; 88 (1969)

Bull. Sot. Chim. Fr. 1972, 690.

Lett. 1973, 2585. Chem. 91 (1979) 938, Angew.

Chem.,

Int. Ed. Engl. 18

(1979)

875.

7.

Racemates

8.

Reviews: a) D. Hoppe, Angew. Chem. 96 (1984) 930; Angew. Chem., Int. Ed. Engl. 23 (1984) 926. b) D. Hoppe in M. P. Schneider (Ed.), Enzymes as Catalysts in Organic Synthesis, p. 177, Reidel Publishing Company, Dordrecht 1986.

9.

D. Hoppe, A. Branneke,

IO.

were used throughout

this work.

Synthesis

1982, 1045.

Preliminary communications: a) D. Hoppe, C. Riemenschneider, Angew. Chem. 95 (1983) 64; Angew. Chem., Int. Ed. Engl. 22 (1983) 54. b) D. Hoppe, C. Gonschorrek, E. Egert, D. Schmidt, Angew. Chem. 97 (1985) 706; Angew. Chem., Int. Ed. Engl. 24 (1985) 700.

II.

D. Hoppe, C. Gonschorrek,

12.

5 was prepared by isomerizatiog from the 2-butynyl carbamate (lOa,ll) by lithiation (1.1 equiv. nBuLi, ether , -78 C), metal Exchange with ClTi(OiPr)3 (1.1 equiv.) and quenching with methanol (5 equiv. at -78 C), yield 63% after LC. Attempts to quench the lithio compound or the use of catalytic LDA resulted in incomplete rearrangement of the starting material.

13.

Correct

14.

Reviews: a) M. T. Reetz, Top. Curr. Chem. 106 (1982) 1. b) B. Weidmann, D. Seebach, An= gew. Chem. 95 (1983) 12; Angew. Chem., Int. Ed. Engl. 22 (1983) 31. c) D. Seebach, B. Weidmann in R. Scheffold (Ed.), Modern Synthetic Methods 1983, Salle, Frankfurt 1983. d) M. T. Reetz, Organotitanium Reagents in Organic Synthesis, Springer, Berlin 1986.

15.

No attempt

16.

syn-10a

17.

CH-analyses

D. Schmidt,

E. Egert,

full paper submitted

to Tetrahedron.

(:0.3%) were obtained.

was made for configurative

assignment

of diastereomers

8.

was obtained from syn-9a (lOa,ll) with LBuMe Sic1 (1.3 equiv.), Et3N and DMAP (0.2 equiv.) in CH2C12, 20 h at 25 "8; yield 76% after LC.

(1.6 Giv.) 1 H NMR (CDC13), syn-14: 6 = 0.05 (s, SiMe2); 0.12 (s, SiMe ); 0.87 (s, SiCMe3); 1.22 (d) and 3.96 (m) (NiPr ); 1.26 (d, J = 6.5 Hz, 5-CH ); ?.7v3(s, 3-CH ); 4.45 ppm in 200 MHz '3 H MR. C NMR &13); z-14: (q, 4-H); anti-14 showzd no differ-e&& 6 = -5.02 and -4.91 (diastereotopic SiMe2); -1.02 (SiMe ); 13.45 (C-5); 18.10 (Sic); 20.45-21.40 and 45.90-46.20 (br., NiPr ); 70.13 (C-4); qll.27 (C-1); 121.44 (C-3); 154.29 (NC=O); 197.13 (c-2); anti-l; ( 8rom the mixture): 14.9z,(C-5); 69.71 (C-4) > 112.43 ppm (C-1). - IR (mixture, neat): 1940 (C=C=C); 1700 cm (C=O).

18.

E. Egert, H. Beck, D. Schmidt, paper.

19.

syn-lla was prepared from =-9a with benzoyl chloride (1.1 equiv.) in pyridine, 3 h at PC, yield 64% after LC, mp 65 OC. The diastereomeric mixture was obtained in the same way from -syn/anti-9a (lOa,ll). 1 H NMR (CDC13); (Z)-16a: 6 = 1.75 (dq, z5 4 = 6 Hz, J = 1 Hz, 5-H3); 1.77 (m, 3-CH 1; 5.60 (m, 4-H); (E)-16a (from :"~,"'1tVs~)lHR.~~~~~.~~~~_~6~.H~,=~~~3io=~~_~~~ 5-H 7; 1.74 (m, 3-CH ); 5.82 ppm (m, 23.33 (3-CH ); 48.593(C-2) ; 92.68 (C-1); 117.58 (C-4); 13036: (z-3); 149.71 (C=O); 16a (from tfle mixture): 13.99 (C-5); 17.43 (3-CH3); 52.17 (C-2); 85.79 (C-1); l~~.l:')(c-4); 131.05 AC-3); 149.74 ppm (c=o). - CT)-16a, IR (KBr): 2250 (C=C); 1755 cm (NC=O); mp 39 C.

20.

C. Gonschorrek,

D. Hoppe, Tetrahedron

Lett.,

subsequent

21.

Cf.: E. Pretsch, J. Seibl, W. Simon, T. Clerc, Strukturaufklarung dungen, 3. Edition, p. H215, Springer-Verlag, Berlin, 1986.

22.

Prepared analogously to ref. 19 from -syn/anti-9b, ratio 80 : 20, yield 77%. This was obtained by desilylation of syn-9c (lOa,ll) (20 mol-2 NaH in THF below 15 OC, followed by methanol and LC); C. Gonschorrek, Dissertation, Univ. of Gettingen, 1985.

23.

(E/Z)-16b, IR (Ccl 1: 2250 (C=C), 1760 cm-' (NC=O). - 'H NMR (CDCl 1; from the mixture, -(z)-16b: 6 = 1.81 ?dd, J = 6.8 Hz, J = 1.8 Hz, 5-H 1; 5.26 (a,, J 3--H); 5.86 (dq, 4-H); (E?d6b: 1.68 (d;r:'s = 6.8 Hz, 5, 3 = 1.8 Hz,-&?I,;;'::;6";:,, = 15.8 Hz, <3 5 = i.3 Hz, 3-H); 6.05-&i (dq, 4-H). ’ J3,4 >

Acknowledgement. The work was supported Fonds der Chemischen Industrie.

(Received

in

Germany

28

November

by the Deutsche

1986)

organischer

Forschungsgemeinschaft

Verbin=

and the