Indian Journal of Chemistry Vol. 41B, January 2002, pp. 161-168

Mechanistic investigation of asymmetric aminohydroxylation of alkenes t

B B Lohray"·b*, Vidya Bhushana.b, G Jaipal Redd/ & A Sekar Redd/

Department of Medicinal Chemistry and Drug Discoveri

aZydus Research Center, Zydus Tower, Satellite Crossroads, Ahmedabad, 3800 15, Indi a *e-mail: braj .lohray @zyduscad ila.com Tel:027 17-3750607; Fax: 02717-3750606

b Department of Medicinal Chemistry and Drug Discovery, Dr. Reddy's Research Foundation, Bollaram Road, Miyapur, Hyderabad 500 050, India

Received 8 May 2001; accepted (revised) 25 October 2001

Transfer of nitrogen and oxygen in asymmetric aminohydroxy lation (AA) has been examined. Electronic as well as steric effect on the nature of ox idizing agent and nitrogen source affect chemo, regio and stereoselectivity in AA reaction. A three cycle mechanistic pathway has been proposed. Results have been rationalized through an addition of alkene to Os=N bond in a [2+2] cycloaddi tion manner.

Asymmetric catalytic functionalisation of isolated alkenes has been a challenging goal for organic chem­ists. In the past decade, we have witnessed a remark­able achievement in the asymmetric dihydroxylation l

and asymmetric epoxidation2• Recently, discovery of

aminohydroxylation of unfunctionalized alkenes3 has added a new dimension to the armory of synthetic organic chemists.

While the mechanistic understanding of asymmet­ric dihydroxylation (AD) and asymmetric epoxidation (AE) of alkenes are reaching maturity, the mechanis­tic study for AA reaction has not been extensively explored. Two catalytic cycle pathways have been proposed in case of AA reaction4, which is remini s­cence of AD reaction.5

The first catalytic cycle as in AD reaction repre­sents a highly stereoselective step, whereas the second cycle not only retards the catalytic turnover but also significantly destroys the stereoselectivity. However, many questions remain unanswered, especially those related to chemo, regio and stereoselective outcome of AA reaction. In the present communication, we report the results of our investigation to answer a few of these questions.

We planned to investigate the effect of (a) steric

2 R1~R +

t ZRC Communication No. 102.

Na-N-[Z] \ -------CI t-BuOH:H20

requirement in AA reaction by changing the size of groups on nitrogen source. (b) Electronic effect in AA reaction, by changing the electron donating and elec­tron withdrawing nature of the groups on nitrogen source. (c) How chloramine T functions as an oxidant in the conversion of osmium (VI) to osmium (VIII) in order to maintain the catalytic cycle. (d) How OS0 4 reacts with chloramine T or other nitrogen/oxidant to generate Os03=N-[Z] (where [Z] is the substituent on nitrogen), which is infact the actual active species for aminohydroxylation. (e) Why the strongly electron deficient olefins are good substrates in AA reaction, whereas reverse is true for AD reaction 7 (f) What is the reason for regioselectivity in AA reaction of al­kenes bearing electron withdrawing substituent at C=C bond6 (g) What is the mode of addition of alkene to trioxoimido osmium complex (030s=N-[Z]). In the present study, we wish to answer a few of these cru­cial questions, which may further help in understand­ing the mechanism of asymmetric aminohydroxyla­tion reaction.

Results and Discussion The reaction of OS04 with chloramine T in

stoichiometric amount was carried out in order to find

+ R,~R' ... (1)

NH[Z]

* Dr. Reddy's Research Foundation, Hyderabad 500 016; part of the present work has been taken from M.Sc. dissertation of GJR.

162 INDIAN J. CHEM., SEC B, JANUARY 2002

o ~O-ipr U ·

1

Chloramine T

DH02PHAL

t-BuOH:H20

ca. 25°C

... (2)

..

Stoich 0504 ---1 .. _ 2 (98 % ee) 3 ( No Amino-Alcohol) ... (3a)

o

~O-ipr

Catalytic 0504 -----' .. ~ 2 (82 % ee)

9H 0 rro-;p, 2: 3 = 14: 86 3 (90 % ee) ... (3b) CH3S02Ht;! 0 +rra-;p,

1

Chloramine M

0504·DH02PHAL ... ca. 25 DC

6. DHO:zPHAL

Chloramine M t-BuOH:H20

ca. 25 DC

..

out if Os03=N-S02-C6H4-CH3(P) is formed as the re­active agent that does aminohydroxylation . The reac­tion was fo llowed by Ff JR . In 0 30s=Nt-Bu complex

the IR freq uency for UOs=N appears as a single band at 1184 cm' l and U Os=O as two bands at 925,9 12 cm' l. In

contrast, UOs=O frequency in OS04 appears at 955 cm'l as single bonds. Following the reaction by Ff IR for 6

hr at ca 30°C, no sign of Os= N-SOr C6H4-CH3(P) appeared in IR spectra indicating that OS0 4 did not react with chloramine T under the experimental con­ditions of ami nohydroxylation. The Os=O signal in IR at 957 cm,l remained unchanged even after 6 hr. Thus, we conclude that initial step may not be the re­action of OS04 with chloramine T or equi valent nitro­gen source. 9

Further, the stiochiometric reaction of OS04 with chloramine T was carried out in the presence of one equivalent of isopropyl cinnamate and ch iral ligand (DHQhPHAL. Surprisingly, no amino alcohol forma­tion was observed (equ . 3a). Nearly quantitat ive yield of isopropyl 2,3-dihydroxy-3-pheny l propanoic acid was isolated in high enantiomeric excess (98% ee).

Thi s clearly suggests that the initial step in the catalytic asymmetric aminohydroxylation reaction is the formation of diol , which generates osmium in the

2 4

2(95 % ee) 2:4=14 : 86 4 (94 % ee) .. . (4a)

2 2: 4 = 7: 93 4 (97 % ee) ... (411)

reduced form Os(VI) . The reduced Os(VI), is then oxidized by chloramine T or other source of nitro­gen/oxidant to generate Os03=NfZ] in which osmium (VI) is oxidized to Os (VIII) and can further react with o lefin. This assumption was further examined by carry ing out the reaction of isopropyl cinnamate at ca 25 °C in t-BuOH-H20 usi ng chloramine T as the source of nitrogen/oxidant in the presence of 10 mole % of OS04. The crude product from the reaction was analyzed by HPLC to determine the ratio of diol and amino alcohol 2:3 (14 : 86) (equ. 3b). Both diol 2 (82% ee) and ami no alcohol 3 (90% ee) were of high enan tiomeric purity (see Table I )

From the above reaction, one would expect to gen­erate only 10 mole % of diol due to the initial asym­metric dihydroxylation step (cJ eq 3a) . In order to es­tablish the origin of formation of diol in more than the expected amount (i n the present case nly 10 % of the diol was expected, since only 10 % of OS04, was used) we repeated the reaction of isopropyl cinnamate with chlorami ne M (CH3S02NNaCI) and Os04.DHQ2PHAL in t-BuOH:H20 (Table I, entry 3). Surpri singly, the ratio of the diol 2 versus amino al­cohol 4 did not change (14:86) (Table I, entries 2 vs 3), although there was considerable improvement in

LOHRA yA er al. : ASYMMETR IC AMINO HYDROXYLATION OF ALKENES

Table 1-Effect of subst ituents on the source of oxidant and Nitrogen in asymmetric aminohydroxylation of cinnamate ester catalysed by Osmium tetroxide and chiral cinchona alkaloid complex .

o

~OR I

Entry L* R

(DHQ)2 PHAL CH)

2 (DHQh PHAL iPr

3 (DHQh PHAL iPr

4 (DHQ)2 PHAL iPr

5 (DHQh PHAL iPr

6 (DHQh PHAL iPr

7 (DHQh PHAL iPr

8 (DHQh PHAL iPr

9 (DHQh PHAL iPr

10 (DHQh PHAL iPr

II (DHQh PHAL iPr

o C}H 0 [Z]NtI _ 0

~OR + rvYOR

V e)H + ~OR V ()H

Nitrogen source

MeD-S~NNaCI

MeD-S~NNaCI CH)S02NNaCI

I

Reaction condition

r-BuOH / H20 10 mol % OS0 4

r-BuOH / H20 10 mol % OS04

2

Ratio of 1:2:3" (% yield)

2

28

3

3

72 (74%)

% ee of 2 and 3

14 (10%) 86 (78%) 82 90c

r-BuOH / H20 14 86 (65%) 95 94d

10 mol % OS04

r-BuOH/H20 12 88(81 %) >96d

10 mol % OS04

r-BuOH / H20 13 (8%) 52 (30%) 35 (20%) 77 66c

10 mol % OS04

r-BuOH/H20 76(53%) 12(9%) 12 (9%) 71 NO IU mol % OS0 4

r-BuOH / H20 75 (60%) 25 (20%) 26 10 mol % OS04

r-BuOH/H20 18(10%) 45(25%) 37(21 %) 10 mol % OS04

r-BuOH / H20 66 (55 %) 34 (25 %) 10 mol % OS04

r-BuOH / H20 86 (80%) 14 (10%) 26 10 mol % OS04

r-BuOH / H20 36 (40%) 18 (15%) 46 (40%) 76 83 f

10 mol % OS04

12 (DHQh PHAL Me EtOCON-NaCI r-BuOH / H20 10 mol % OS04

5 % 95 (66%)

13 (DHQh PHAL Me CBzNNaCI r-BuOH / H20 4 mol % OS04

14 (DHQh PHAL iPr TMS(CH2h OCONNaCI r-BuOH / H20 4 mol % OS04

4 % 96 (65 %)

4 % 96 (70%)

163

(a) Ratio of the starting material, diol and amino alcohol was determined by HPLC using C 18 reverse phase column. Enantiomet­ric excess of major products were determined by HPLC using chiral column. (b) Ref. 6a (c) determined by HPLC, using chiracel AD column at 210 nm, 30 % i-PrOH/ H20 I ml / min flow rate. (d) ref 6b. (e) analyzed by chiracel 00 column. (f) used chiracel 00 column. 1.0 ml / min flow rate isopropanol : water (g) ref 10. h) ref 7. i) ref 12a

the enantiomeric excess of both diol 2 (95 % ee) as well as amino alcohol 4 (94 % ee) (equ 4a).

In order to understand the diol and amino alcohol forming catalytic pathways, we prepared osmium gly­colate ester 6 of allyl acetate by the reaction of OS04 with allyl acetate 4 in dry toluene as a dark green powder (equ.5) .

The osmate ester 6 (J 0 mole %) was used as a cata­lyst in the aminohydroxylation of isopropyl cinnamate

0 ':::::-0 -70

/ 5 ~OAc + 050

4 ----I .. ~ 0 .... 0 ... (5) ~OAC

5 6

1 in the presence of DHQ2PHAL and Choramine M (CH3S02NNaCl) as the source of nitrogen/oxidant. Interestingly, the formation of diol 2 was still ob­served albeit in much lower proportion (diol : amino

164 INDIAN J. CHEM., SEC B, JANUARY 2002

alcohol 7:93) (cj equ . 4b). The ami no alcohol 4 thus formed in this reaction has enantiomeric excess of >97 % (equ 4b). This suggests that although the first step in AA reaction is the reaction of OS0 4 L * with olefin to generate diol, there exist still another route through which diol fo rmation is taking pl ace and that could be possibly either a) through the hydro lysis of Os03=N[Z] to OS0 4 or b) the reaction of olefin with O=Os=O rather than O=Os=N[Z] , which is subse­quently hydrolyzed to give diol. In e ither of the cases, the nature of [Z] group on the nitrogen wou ld tremen­dously influence the formation of diol. Thus, we de­cided to examine the effect of substituents on [Z]-N.

We carried out amino hydroxylmion of methyl cin­namate in t-BuOH-H20 (1: 1) using DHQ2PHAL (12.5 %) and OS0 4 (10 %). The analys is of the crude reac­tion mixture by HPLC indicated the formation of diol and amino alcohol in 28:72 ratio (Table I, entry 1). The reaction mixture was chromatographed and both the diol and amino alcohol were isolated. Similarly, the reaction was repeated using isopropyl cinnamate as the substrate . The diol and amino alcohol were iso­lated by chromatography. The dio l was converted into bis-acetate and was analyzed by HPLC on chiral col­umn Lichro Cart (S,S)- whelk 01 (5 11M) to determine the enantiomeric excess. Similarly, amino alcohol was converted to the corresponding acetate and was ana­lyzed by HPLC using chiralcel 00 column to deter­mine the enantioselectivity. The use of isopropyl cin­namate as the substrate lead to an improved ratio of diol versus amino alcohol (14:86). The enantiomeric excess of amino alcohol was found to be 90% whereas diol was of 82% ee. Thus, change of methyl cinnamate to isopropyl cinnamate led to an improve­ment in chemo and stereoselectivity. Further, we car­ried out the amino hydroxylation of isopropyl cinna­mate using chloramine M in t-BuOH-H20 (1: I) and 10 mole % of OS0 4 and examined the ratio of dio l versus amino alcohol (Table I, entry 3) . Interestingly, the ratio of diol and amino alcohol was found to be unchanged (14:86) although the reaction proceeded much fas ter and with higher enantiomeric excess of both diol and amino alcohol suggesting that the smaller nitrogen source is a preferred oxidant. The intermediate L * 0 30 s=N-S02CH3 undergoes rapid reaction with alkene to form azaglycolate which hy­drolyses to furnish amino alcohol.

We further examined the effect of substituent on the source of nitrogen. The reaction of isopropyl cin­namate was carried out with N-bromoacetamide and 10 mole % of OS0 4 in t-BuOH-H20 (1: 1) and the ratio

of d io l versus amino alcohol was determined by HPLC.6 As expected the ratio of diol : amino alcohol was 12:88 which further supports the fact that 10 % of diol is generated by the reaction of 10 mole % OS0 4 with isopropyl cinnamate (Table I, entry 4). The en­antiomeric excess of amino alcohol was found to be greater than 96%.4 Further, we replaced N-bromo­

acetamide with a -chloro-N-bromoacetamide (Table I, entry 5). Interestingly, there was a dramatic change in the reac tivity and selecti vi ty of the reaction . Under the experimental conditions used fo r N-bromoacetamide,

use of a-chloro-N-bromoacetamide led to the forma­tion of a considerable amount of diol at the expense of amino alcohol along with 8% recovery of the starting material. HPLC analysis of the crude reaction mixture suggested the ratio as shown in Table I (entry 5). The enantiomeric excess of both diol (77%) and amino alcohol (66%) was found to suffer. In continuation with this study, we carried out the reaction of isopro­

pyl cinnamate with a,a-dichloro (Table I entry 6) and a,a,a-trichloro N-bromo-acetamide (Table I en­try 7) under similar conditions. In the former case only small amounts of dio l (9%) and amino alcohol (9%) were formed along with 53% recovery of start­ing material (Table I, entry 6) , whereas in the latter case formation of amino alcohol wa not observed at all. Surpri singly, the enantiomeric purity of dial was also significantly low (Table I, entry 7, 26% ee of diol) . In both the cases, considerable amount of un­changed starting material (53-60%) were isolated , indicating a remarkable drop in reac tiv ity and selec­

tivity of the amino hydroxylation reaction usi ng a­substituted-N-bromoacetamide. Similar results were

observed by using a -f1uoro-N-bromo-acetamide and a,a,a-trifluoroacetamide (Table I, entries 8 and 9). These two sets of experiments suggest that electronic factor plays a very crucial role in changing the course of reaction. Since the ratio of d io ls versus amino al­cohol was not drastically different by changing a­chloro-N-bromoacetamide or a,a,a-trichloro-N-bro­moacetamide to the corresponding f1uoro substituted analogs (Table I , entries 5 vs 8 and 7 vs 9), it appears that steric effec( plays a secondary role in the chemoselectivity of the reaction. If one compares re­sults from a,a,a-trifluoro-N-bromoactamide with un­substituted N-brornoacetamide (Table I, entries 9 vs 4), a dramatic change in the selectivity of the reactio n is seen. This change in the selectivity and the reactiv­ity cannot be justified based on their steric bulk, since

a,a,a-trifluoro or a-f1uoro-N-bromoacetamide are not

LOHRAyA el al. : ASYMMETRIC AMINO HYDROXYLATION OF ALKENES 165

significantly different from N-bromoacetamide. In order to observe the pronounced effect of steric bulk, we carried out amino hydroxylation reaction of iso­propyl cinnamate with a,a,a-trimethyl-N-bromo­acetamide (Table I, entry 10). No amino alcohol was formed, only 10% yield of diol (26% ee) was detected along with 80% recovery of the starting material by HPLC analysis .

From the above results, it appears that sterically small and electron donating substituents on N­bromoacetamide may favor the formation of arruno alcohol and reduce the formation of diol. Therefore, electron donating substituents such methoxy was intro­duced at the a-position of N-bromoacetarrude in order to exarrune the validity of our argument. We prepared a-methoxy-N-bromoacetamide and carried out arruno hydroxylation of isopropyl cinnamate using 10 mole % of OS04 and 12 % mole of DHQ2PHAL. Unfortu­nately, the reaction was quite slow, although amino alcohol was formed in 40 % yield (83 % ee), along with 15 % of diol (76 % ee) and 40% recovery of un­changed isopropyl cinnamate (Table I, entry 11).

We further examined the ratio of diol versus amino alcohol using 4 mole % of OS04 and sodium salt of N­chloro-ethyl carbamate and N-chloro-benzyl car­bamate (Table I, entries 12, 13).10.11 No unreacted

First cycle

(high enantioselectiviy) -:.-... I Diol generating Cycle r--\.

HO N-Z

starting material was observed but analysis of the crude reaction mixture by HPLC suggested the forma­tion of diol (4-5 %) in both the cases.

Similarly, use of recently reported 12 nitrogen source, N-chloro-N-sodium-2-trimethylsilyl ethyl car­bamate (Table I, entry 14) lead to the formation of diol versus amino alcohol in 4:96 ratio. The amount of OS04 can be reduced to 2 mole % if trimethylsilyl ethyl carbamate is used as the source of nitro­gen/oxidant. It appears that it is possible to eliminate the formation of diol of the substrate in use by using dioxoosmium glycolate ester as the source of Os(VlIl) and N-chloro-N-sodio-2-trimethylsilyl ethyl car­bamate or N-chloro-N-sodio methane sulfonamide (chloramine M) as nitrogen source l2 (Table I, entries 14 and 3).

In both the cases, the amount of diol generated can be accounted for based on the % mole of OS04 used in the reaction. If OS02[ -OCH2CH20-] is used as a catalyst, the glycol generated thus in the reaction could be easily washed out from the reaction mixture with water.

Based on these results, we propose a catalytic sys­tem comprising of three catalytic cycles (Figure I). The initial cycle is the rapid reaction of Os04L * 7 with olefin to generate a glycolate ester 8, which is

L* o H Iko __ ~H-I L-o~/ HO OH /Os~ H20 Js ~o-'y"'" 0/' N-Z Z 0

, N ....... Z L* I L* ~ 0" 11 0 H20 10 .\:LN""dJ,,'Oy 0( ~ /os ':"~ Second cycle Z 0- I 'N \

., 0/ L. (high enantioselectivity) N11-- If '

CI j Amino alcohol o~ _o~ / Third cycle i Z

9 'i s, 'NY' H20. L Z 0 L* 1 (lowenantioselectivity)

ftJ 0 llZ~Aminoalcohol o~or~~ Z yOH

~ 0 0, ~ 12 N /o'J~:=y( ~H

z/ .......... CI 0 / I 0 Z

L* 12

Figure 1 - Three cyc le Asymmetric Diol and Amino Alcohol generating pathways

166 INDIAN J. CHEM .. SEC B. JANUARY 2002

oxidized by electron deficient nitrene to give a osmate ester 9, (first cycle). The osmate ester 9 can be readily hydrolyzed by water to give the diol and trioxoimide osmium (VIII) 10. Depending on the nature of imido ligand, the reactive osmium (VIII) 10 species either reacts with olefin to give a azaglycolate ester 12 or gets hydrolyzed with water to give Os0 4L * 7. If OS0 4 L * 7 is generated, it can react repeatedly with olefin to generate more and more diol (first cycle).

In contrast, the azaglycolate 12 can get further oxi­dized with nitrene oxidant N[Z] to give azaglycolate osmate ester 11, which can hydrolyze with water to generate amino alcohol (second cycle) and regenerate trioxoimido osmium (VIII) 10. On the other hand, if the azaglycolate ester 11 reacts with a further mole­cule of alkene to give bisazaglycolate 13 (third cycle), then the reaction will proceed through the non­selective pathway to generate racemic amino alcohol4. These three catalytic cycles very well explain the for­mation of diols and suggest a possible method to eliminate the formation of diol as well.

Further, several other facts can be explained based on the above catalytic cycle prolPosed. The osmate (VI) glycolate 8 can react with electron deficient nitrene by the transfer of electron and get oxidized to Os (VIII) which leads to the formation of glycolate ester 9. This intermediate is susceptible to hydrolysis to generate the diol and give Os0 3=N-Z 10. In this L*Os(VIII)=N-Z intermediate, Os=N bond is polar­ized and may exist in tautomeric forms (lOa -10c) as shown in equation 6 and may act as a nucleophile.

Thus, the intermediate 10 would add on an electron deficient alkene in a Michael mode more favorably to give a Michael adduct 14a or 14tb and therefore, it will give an adduct in which the nitrogen is attached to carbon (3 to the electron withdrawing group (Scheme I). This mechanism explains well why such regioselectivity is observed in the case of alkenes at­tached to electron withdrawing substituents, such as a,(3-unsaturated esters etc.

This also explains why electron deficient alkenes are preferred substrates in AA reaction and also the possible reason for their regioselectivity. In contrast, in the case of electron rich alkenes, no special prefer­ence may be possible and the observed regioselectiv-

ity may be emerging from purely steric selection. Therefore , electron rich alkenes do not show any spe­cial preference for the attack by osmium complex and hence, results in a mixture of regio-i somers 12a and 12b via the intermediacy of lSa and lSb (Scheme II). Good regioselectivity observed in the case of electron rich alkenes is purely due to the steric bias by the sub­strate-osmium complex transition state in the AA re­action.

Finally, this mechanism also gives a clue that the reaction of trioxoimido osmium (VIII) to give amino alcohol may be proceeding via a [2+2] cycloaddition reaction as shown in Scheme II and not via [3+2] ad­dition pathway. The reaction of 10 with an alkene substrate should lead to tautomeric structures 14a or 14b but, very unlikely 14c or 14d, since the formation of 14c or 14d arises due to the delocalization of the partial positive +8 charge on the electronegative oxy­gen atom of L*0 30sN-[Z]-[Sub]. Thus, the tauto­meric form 14a or 14b may be favored and result in a four membered neutral osmoazetidine intermediate lSal1Sb which may undergo rearrangement to a sta­ble five membered adduct 12a112b.

Thus, the present mechanistic proposition supports [2+2] cycloaddition of oxoimido osmium (VIII) with alkenes, which can explain all the results observed so far. Further research in this direction is continuing in order to get better conditions for improved chemo, regio and stereoselectivity in AA reaction.

Experimental S,ection Solvents were of reagent grade and used without

puri fication . Commercial reagents were used without purification. Chloramine T, Chloramine M,1 3 N­bromoacetamide,14 a-dichloro-N-bromoacetamide,15 a,a,a, -tri tl uoro-N-bromoacetamide, ,5 a,a,a, -tri methy 1-N-bromoacetamide'5, a-methoxy-N-bromoacetamide, ,6

trimethylsilylethyl carbamate 12a were prepared ei ther by reported procedure or purchased from Aldrich. Methyl cinnamate, isopropyl cinnamate, ethyl car­bamate, benzyl carbamate, osmium tetroxide, DHQ2PHAL were purchased from Aldrich.

Melting points were determined in a Thomas­Hoover Capillary Melting Point apparatus and are uncorrected. IH NMR spectra were recorded on a

o 0 0 -o II 0 - II 0 I *L -. II N-S-CH *L 11+ N-S-CH3 *L"I:+ .... N=S-CH3 OS'l .. 3 'OS.... II OS II //~O ~b 0 '::;;;;r===h!!::::.h o 0 O~ ''0 • O~ ''0 0

... (6)

10a 10b 10c

LOHRAyA et al.: ASYMMETRIC AMINO HYDROXYLATION OF ALKENES 167

o L* 11/ 0 O:::::Os~ ~/CH3 0' 'N/ ~

i-prO~ 0

o Ph

12 Scheme I

15

0 -* 0 iJ b .. II + ..... N=S- CH3 __

,.;O~ •• II O{/ '-':0 \ 0

"'- R2 1~

10 R

+

Varian 200 MHz spectrometer. Optical rotation was measured using a Jasco polarimeter in various sol­vents . Flash chromatography was performed on SRL-230 mesh size silica gel. HPLC was performed on a chiral column and products were detected at 254 nm. All the reactions were carried out in t-BuOH : water (1:1) mixture using 2-10 % mole of OS04 as catalyst

at room temperature ca 28 °C. Preparation of catalyst 6. In a 5 mL scintillation

vial was placed 25.4 mg (0.1 mmole) of osmium tetroxide in 2 mL of dry toluene. Allyl acetate (10 mg,

+

L +

0.1 mmole) dissolved in 100 ~L of toluene was added through a syri nge. The reaction mixture was gently shaken and allowed to stand at room temperature for 1 hr. A black precipitate was formed . The reaction mix­ture was diluted with 2 mL of dry hexane, filtered and dried to afford osmate ester of allyl acetate 6 (30 mg, 85 %).

General procedure for asymmetric amino­hydroxylation (AA). All AA reactions repolted in the Table I were carried out in the following manner on 1 mmole scale. A 20 mL scintillation vial equipped with

168 INDIAN J . CHEM ., SEC B, JANUARY 2002

a magnetic bar was charged with a solution of appro­priate nitrogen/oxidant source (e.g. chloramine M, CH3S02NNaCl, 455 mg, 3 mmole, 3.0 equivalent) in 7.5 mL water, 7.5 mL t-BuOH and 40 mg (0.05 mmole, 0.05 equivalent) of DHQ2PHAL. To the result­ing clear solution, OS0 4( 10.16 mg, 0.04 mmole, 0.04 equivalent in 100 ilL of toluene) followed by isopropyl cinnamate (l90mg, 1.0 mmole) were added. After a few min., the reaction mixture turned green, and the stirring was continued at co 25 °C until the reaction mixture had turned clear yellow. In several cases even after several hours, a clear light yellow solution was not obtained. The reaction was terminated by an addi­tion of 10 mL of saturated aqueous Na2S03 (exother­mic reaction, cooling may be required) . The reaction mixture was stirred for co 15 min . The organic phase was separated and the aqueous phase was extracted with ethyl acetate (3 x 25 mL). The combined organic phase was washed with brine (25 mL), dried over an­hydrous Na2S04 and concentrated to afford the crude product. The crude product was analyzed by HPLC to determine the ratio of diol and amino alcohol.

The crude reaction mixture was then purified by flash chromatography to afford diol and amino alco­hol in pure form . The enantiomeric excess of the diol and amino alcohol were determined by various meth­ods as described in Table I.

Acknowledgement We are grateful Dr Reddy's Research Foundation,

Hyderabad for support. We also thank Shri . P. R. Patel, Managing Director, Cadila Healthcare Ltd, for encouragement.

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7 Tao B, Schlingloff G & Sharpless K B, Tetrahedrol/ Lell, 39, 1998,2507.

8 Chong A 0, Oshima K & Sharpless K B, jAm Chem Soc, 99, 1977,3420.

9 OS04 is known to react with t-BuN H2 eas il y to give 030s=N-t-Bu (Patric D W, Truesdale L K, Bi ller S A & Sharpless K B, J Org Chem, 43, 1978, 2628) . In contrast, c hloramine T or c hl oramine M generate e lectron deficient nitre ne spec ies as the source of oxidant wh ich is an e lectro­phile and Os (VI) can react with these nitrenes by transfer of e lectron to generate Os (V III ). Several exa mpl es ol reac­ti ons of c hloramine T with Cu (I) to generate reacti ve nitrene species are known. The nitrene subseque ntly reacts with o le fin to furnish az irid ine. (Vyas R, Chanda B M, & Bedekar A V, Tetrahedron Lell, 39, 1998,4715; Ando T, Minakata S, Ryu I & Komatsu M, Tetra hedron Lell. 39, 1998,308; Ando T , Kano D, Minaka ta S . Ry u I & Komatsu M, Tetrah edron 54, 1998, 13485).

10 Li G, Angert H H & Sharpless K B, Angew Chel1l /l1t Ed Engl, 35, 1996, 28 13.

II (a) Herranz E, Biller A & Sharpless K B, J Am Chem Soc, 100, 1978, 3596. (b) Hentges S G & Sharpless K B, J Org Chel1l, 45, 1980, 2257.

12 (a) Reddy K L, Dress K R & Sharpless K B, Tetrahedron Lell, 39, 1998, 3667. (b) Reddy K L & Sharpless K B, J Am Chem Soc. 120, H998, 1207.

13 Hardy FE, J Chem Soc, 1970, 2087. 14 Pli veto E P & Gerold C, Org Synth, Coli Vol IV, John Wiley

& Sons (New York) , 1962,1 04. 15 (a) Gottardi W, MOl/atsh Chem, 106, 1975,6 11 -623. b) Got­

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