Steric control of epoxidation by allylic and homoallylic carbamate groups

Tetrahedron Letters,Vo1.29,No.20,pp2475-2478,1988 Printed in Great Britain

STERIC CONTROL OF AND

0040-4039/88 $3.00 + .OO Pergamon Press plc

EPOXIDATION BY ALLYLIC

HOMOALLYLIC CARSAMATE GROUPS

Pave1 Koi?ovsk$

Institute of Organic Chemistry and Biochemistry Cxechoslovak Academy of Sciences, 166 10 Prague 6, Czechoslovakia

Abstract: Carbamoyloxy groups show m-stereodirecting effect on epoxidation of allylic and homoallylic double bonds similar to that of hydroxy groups. Allylic carbamates $-l-f, 4,d, 62, and Lf and their homoallylic counterparts $c-8-ethus produce corresponding &-epoxides as the major products on reaction with MCPBA. Mechanism of this steering is discussed.

Epoxidation of m-fashion1

cyclic allylic alcohols (e.g. 2)

giving a-epoxides2.

In

is known to proceed in a

contrast, allylic esters

(2) produce

trans-epoxides under the same conditions' (Scheme 1). Here we describe m-stereodirecting effect of various carbamoyloxy groups similar to We have

that of hydroxyl.

found that carbamates derived from allylic alcohols 1 and 4 are

predominantly oxidised with CHC13 at O'C from the B-side

m-chloroperoxybenxoic acid

(MCPBA) id

to give the corresponding a-epoxidesz Compound

3

cis/trans

CONEI

3 :l

CONHCH2Ph

5 : 1

le

CONHTs

3 :l

If

CONMe

10 :l

9

H

4d C

CONHCH2Ph >20 : 1

-

2475

and2 as

J.z Id C

Scheme 1

R

cH,c’;, or

>20 : 1

2476

products (Scheme 1 and Table) 3,6,7

the major

. It turned out that this effect is

strong enough to override the steric bias of the steroid skeleton, whose is usually

less hindered*,

and to drive the epoxidation to occur predominantly

from the S-side (Scheme 2). Thus the steroidal carbamates 2 a-epoxides

a-side

and 6_f afford the

7 as the sole products similarly to the parent alcohol 6a. Compound

6

1

R

6d

CONHCH2Ph

>20 : 1

6f -D-

CONMe

>20 : 1

Scheme 2 This steric control appears not to be confined to allylic carbamates, but can be observed with some homoallylic derivatives. Thus 19-carbamoyloxy ($), zyl carbamoyloxy dation from the 9. Note

(82), and 19-N-tosyl carbamoyloxy (2) B-side which leads to

that carbamates z-82

parent alcohol 2.

19-N-ben-

groups steer the epoxi-

predominant formation

of 5R,6R-epoxides

furnish even higher cis/trans ratio than does the

This neighboring group effect is,

however, considerably less

manifested with the N,N-dimethyl carbamate Lf (Scheme 3 and Table).

Compound

10

8f rc-

R

Ratioz/g

H

5:l

PhCO

1 : 10

H2NC0

6:l

PhCH2NHC0

>lO : 1

TsNHCO

>lO : 1

Me2NC0

1:2

Scheme 3 Our findings show that the carbamate group can serve as an alternative to 11 . This behavior raises the questhe hydroxyl in steric control of epoxidation tion as to the mechanism. The steering effect of hydroxy group was attributed by . Henbest to the hydrogen bonding between OH and the reagent' and since then this mechanism

has been widely

accepted2. Similar

des12 was rationalized by analogous methyl carbamoyloxy group

ayn-epoxidation of

NH-bonding13. However,

allylic ami-

our allylic N,N-di-

in If and 6f cannot offer any OH or NH and still conC

2477

trols

the

epoxidation

in

a

m-fashion.

Therefore an alternative mechanism

should be suggested to account for this behavior. bonding in

a reversed

way, i.e.

We can

speculate on hydrogen

from the reagent (HCPBA) to one of the oxygen

atoms of the carbamate group (Scheme 4). Although the ether

oxygen seems

to be

an entropically better candidate (A), the carbonyl oxygen in carbamates is known 14 to be much stronger nucleophile and might also play a role in binding the i5 electrophile (B). Participation of the nitrogen lone-pair does not seem probable 14 in the light of general reactivity of the carbamate and amide groups . Another mechanism can simply involve Coulombic interaction of the electrophile with nucleophilic allylic

center16. Further

study of

this issue is

the

in progress in

this Laboratory.

Scheme 4 In principle, the m-carbamoyloxy

epoxides 2, i,L,

and _9

could also be

synthesized in the reversed way, i.e. by epoxidation of allylic alcohols followed by derivatixation with the corresponding

isocyanates. However,

alcohols do not react cleanly with isocyanates (particularly 2) amounts of by-products. Furthermore, epoxides Lf,

zf, andzf

preparation of

some epoxy

and give large

N,N-dimethyl carbamoyloxy

would require drastic conditions (cf. ref.5) which are

not compatible with this sensitive functionality. Our epoxidation of carbamates thus seems

to be

a cleaner process. Moreover,

diastereoselectivity of epoxi-

dation of certain carbamates is better than that of the parent alcohols. As the carbamate groups have been frequently employed to control the opening of oxira17 ne ring we believe that our stereocontrolled epoxidation method may become a useful alternative for the stereoselective synthesis of epoxy carbamates. References and Notes 1. (a) Henbest A., Wilson R.A.: J. Chem. Sot. 1958 (1957); (b) Katsuki T.,

Sharpless K.B.: J. Am. Chem. Sot. 102, 5974 (1980). For review see e.g.: Koc'ovsk$ P., Turegek F., Hijic'ek J.: "Synthesis of Natural Products : Problems of Stereoselectivity", Vol. I and II, CRC Press, Boca Raton FL, 1986. 3. Carbamates 1,"and 8,cwere prepared by our new method', i.e. by reaction of alcohols with trichloroacetyl isocyanate followed by hydrolysis on alumina. N-Benzyl carbamates 1, 43 z, and s were obtained from the alcohols by

2.

2478 treatment with benzyl isocyanate at r.t. for 3 days. Shorter time (several minutes) was required for prepartion of N-tosyl carbamates 12 and 82. Preparation of N,N-dimethyl carbamates 12 and Lf required reaction of Li-sal$s of the alcohols with Me2NCOC1 in agreement with the Overman's observation . Synthesis of Lf was more complex and included several steps, as the presence of the acetoxy group was not compatible with the method of generating the lithium salt (details will be published in full paper). 4. Ko
For further examples see e.g.: (a) Takeda K., Hamamoto s., Sasaki K., Maezono N., Murabayashi A.: Stel_oids2, 27 (1963); (b) Cerny V., Bud;&sk$ M., Ryba M., Turec'ekF.: Collect. Czech. Chem. Commun., in press (1988). 16. For discussion and quantum chemistry calculations of electrophilic additions to allylic systems see: (a) Kahn S.D., Hehre W.J.: J. Am. Chem.Soc. &Q$!,666 (1987); (b) Chamberlin A.R., Mulholland R.L.,Jr., Kahn S.D., Hehre W.J.: J. Am. Chem. sot. m, 672 (1987). 17. For recent synthetic applications of epoxy carbamates see ref.5,13c, and: (a) Minami M., Ko S.S., Kishi Y.: J. Am. Chem. Sot. m, 1109 (1982); (b) Roush W.R., Di Mare M.: J. Ors. Chem. 48, 5083 (1983); (c) Roush W.R., Brown W.R.: ibid., 5093; (d) Roush W.R., Adam M.A.: ibid. a, 3752 (1985). (Received

in UK 9 March 1988)