Method of preparing (3R,4S)-3-acetamido-4-allyl-N-(tert-butyl)pyrrolidine-3-carboxamide

1. An amine compound represented by formula I:

wherein:

X is O, S, or NR e ;

R a is H, lower alkyl, or lower cycloalkyl;

R b is —CH 2 CH═CH 2 , —CH 2 CH 2 CH 2 Z 1 , —(CH 2 ) n C(O)H, or —(CH 2 ) n CO 2 Z 2 ;

R c and R d are independently H, lower alkyl, lower cycloalkyl, silyl, acyl, acyloxy; or R c and R d , together with the N that links them, form an optionally substituted 3- to 6-membered heteroaryl or heterocyclic ring;

R c is H or lower alkyl;

n is 1 or 2;

Z 1 is halogen, alkyl sulfonate, aryl sulfonate, or an alkyl sulfonate optionally substituted with one or more halogen; and

Z 2 is H, lower alkyl, or lower cycloalkyl;

wherein the amine compound has an enantiomeric excess of greater than 75% ee.

2. The amine compound of claim 1 , wherein R a is tert-butyl.

3. The amine compound of claim 1 , wherein R b is —CH 2 CH═CH 2 .

4. The amine compound of claim 1 , wherein R c is H.

5. The amine compound of claim 1 , wherein R d is acetyl or trifluoroacetyl.

6. The amine compound of claim 1 , wherein X is NH.

7. The amine compound of claim 1 , wherein X is O.

8. The amine compound of claim 1 , wherein the amine compound is:

wherein R f is H, lower alkyl, or lower cycloalkyl.

9. The amine compound of claim 1 , wherein the amine compound has an enantiomeric excess of between 90% and 99.5% ee.

10. The amine compound of claim 1 , wherein the amine compound is:

11. The amine compound of claim 1 , wherein the amine compound has an enantiomeric excess of greater than 97% ee.

12. The amine compound of claim 8 , wherein the amine compound has an enantiomeric excess of between 90% and 99.5% ee.

13. The amine compound of claim 8 , wherein the amine compound has an enantiomeric excess of greater than 97% ee.

14. The amine compound of claim 8 , wherein the amine compound has an enantiomeric excess of greater than 99% ee.

15. The amine compound of claim 10 , wherein the amine compound has an enantiomeric excess of between 90% and 99.5% ee.

16. The amine compound of claim 10 , wherein the amine compound has an enantiomeric excess of greater than 97% ee.

17. The amine compound of claim 10 , wherein the amine compound has an enantiomeric excess of greater than 99% ee.

18. A process that uses the amine compound of claim 10 to prepare an arginase inhibitor of formula III:

wherein G is H, methyl, isopropyl, sec-butyl, —CH 2 CH(CH 3 ) 2 , benzyl, p-hydroxybenzyl, —CH 2 OH, —CH(OH)CH 3 , —CH 2 -3-indoyl, —CH 2 COOH, —CH 2 CH 2 COOH, —CH 2 C(O)NH 2 , —CH 2 CH 2 C(O)NH 2 , —CH 2 SH, —CH 2 CH 2 SCH 3 , —(CH 2 ) 4 NH 2 , —(CH 2 ) 3 NHC(═NH)NH 2 , or —CH 2 -3-imidazoyl;

said process comprising:

(a) providing the amine compound of claim 10 :

wherein the amine compound has an enantiomeric excess greater than 80% ee;

(b) adding a protecting group to the secondary amine of the amine compound provided in step (a) to form the following compound:

wherein the protecting group (Pg) is formyl, acetyl, trifluoroacetyl, benzyl, benzyloxycarbonyl, tert-butoxycarbonyl, trim ethyl silyl, 2-trimethylsilyl-ethanesulfonyl, methoxymethyl, triethylsilyl, triisopropylsilyl, tert-butyldimethylsilyltrityl, trityl, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, or nitro-veratryloxycarbonyl;

(c) subjecting the compound prepared by step (b) to hydroboration conditions;

(d) removing the secondary amine protecting group from the compound prepared by step (c);

(e) subjecting the secondary amine of the compound prepared by step (d) to an amidation reaction; and

(f) subjecting the compound prepared by step (e) to conditions sufficient to form the compound of formula III;

wherein the compound of formula III prepared by the process has an enantiomeric excess of greater than 80% ee.

19. The process of claim 18 , wherein the amine compound provided in step (a) has an enantiomeric excess greater than 90% ee.

20. The process of claim 18 , wherein the compound of formula III prepared by the process has an enantiomeric excess of greater than 90% ee.