Dear

Sameer,

Please find this  Organic Chemistry By Marye Anne Fox, James K. Whitesell I hope my this link is helpful for you.

https://books.google.co.in/books?id=xx_uIP5LgO8C&pg=PA615&lpg=PA615&dq=Grignard+reagent+from+amino+acid?&source=bl&ots=gmcEhkrCZj&sig=VAcYKLUO6ZN4-xR52rsJ05gfEZk&hl=en&sa=X&ved=0ahUKEwih-Ir_8v3MAhUF8RQKHdA3Cl4Q6AEILzAD#v=onepage&q=Grignard%20reagent%20from%20amino%20acid%3F&f=false

Hi

A new synthesis of -amino-acids by the reaction of Grignard reagents with ethyl N-trichloroethylidenecarbamate. Journal of the Chemical Society Perkin Transactions 1 7(23) · January 1975

Best wishes

Yes, you could; but you need to try! Chemistry is all about trying!!

Talaat I. El-Emary sir, Thanks for answer. But my question is about synthesizing a RMgX from amino acid.  

You mean that u want to prepare Grignard reagent from amino acid ?. You should first convert the NH2 group  by diazotizing it using NaNO2/HCl into OH group. Then you sholuld eliminate the COOH (u decarboxylate it). Then brominate or chlorinate your product after removal of COOH and then react it with Mg metal in dry ether,

Best wishes

Talaat I. El-Emary  sir. Thanks for your reply. Sir, I am planning a total synthesis of one natural product in which I want to do a addition reaction of alpha amino acid on carbonyl of ketone. The main condition here is that I want both carboxyl and amino functionality for next step in synthesis. Can I go for Barbier type reaction for this goal. But I think the barbier type reactions goes only with allylic system. Please suggest.   

Dear Sameer

As u mentioned The Barbier reaction is an organic reaction between an alkyl halide and a carbonyl group as an electrophilic substrate in the presence of magnesium, aluminium, zinc, indium, tin or its salts. The reaction product is a primary, secondary or tertiary alcohol. The reaction is similar to the Grignard reaction but the crucial difference is that the Barbier reaction is a one-pot synthesis whereas a Grignard reagent is prepared separately before addition of the carbonyl compound. Barbier reactions are nucleophilic addition reactions that usually take place with relatively inexpensive and water insensitive metals or metal compounds in contrast to Grignard reagents or organolithium reagents. For this reason it is possible in many cases to run the reaction in water which makes the procedure part of green chemistry. The Barbier reaction is named after Victor Grignard's teacher Philippe Barbier

So, to generate Grignard type reagent from amino acid with preserving both  NH2 and COOH is somewhat strange. You know Grignard type reagent is coming from the reaction between alkyl halide and Mg metal in dry ether. So, the question is how to generate alkyl halide from your amino acid?

Best regards

The grignard reagent can never coexist with the NH of the protected amino group. You would have only a chance with a protecting group with protects both hydrogen of the aminogroup. Such a protecting group would be the phthalimide or a Schiff base. Also the ester group of the carboxylic acid is not stable in presence of a grignard reagent. Instead of Grignard you can try a metallization with BuLi at -78°C and transmetallization with MgCl2 or ZnCl2.

Talaat I. El-Emary sir, What if I use a primary alcoholic group of serine to convert it in halide and then this generated halide is used for grignard type reagent? 

Dear Sameer

I don't know exactly what could happened if u try to do this idea. However, the suggestion provided by Prof. Burkhard Koehler to try to metallization with BuLi at -78°C and transmetallization with MgCl2 or ZnCl2 looks good.

Well, the suggestions by Drs. El-Emary and Koehler are good and you should think and focus in that direction! Primarily, the structure provided in your question is not feasible for the GR. The alternate metallation route suggested by Dr. Koehler is different than the one you were looking with the GR and it is different in its routing to product, mechanism and handling chemistry. The primary alcohol of serine will pose the same dilemma for you which Dr. Kohler pointed out with respect to the amino, carboxyl and their protected formats not going in the GR. The alternates in protections other than suggested by you need to be fully covering up the reactivity (all H cover and O reactivity diminished and controlled) of these groups and as suggested need be phthalimide etc. You could check the protecting group text by Greene also for further insight.

Thanks for your valuable suggestion Riaz Khan sir. 

The answers provided by Dr. Riaz A. Khan should be taken into consideration.

Dear Sameer. Please consider using the Liebeskind-Srogl reaction. Boronates and thioesters are synthetically quite accessible, and you may be able to avoid all that protection/deprotection stuff. Appel to brominate, Miyaura to borylate. Suggest you control pH to avoid nucleophilic attack of amine on bromide. Good luck!

You have to consider some of these general and specific points: Will it be able to retain the amino acid entity, your original substrate in which you are interested? Synthons change is fine for new bond formation but is the thioester and boronic acid generation feasible for this substrate? and how to do it? if at all you even try to do it? Is it going to prolong the reaction sequence of synthesis to arrive at the desired product (may or may not depending upon the starting, route, and synthons used)? Is the atom economy OK? Is the reaction cost and time-effective? Is it feasible to run and the process is robust to withstand physico-chemical parameters change? Will it be OK to scale-up which, it seems, is required to proceed further in your synthesis? Although some of these points may be/are positive but, nonetheless, what about the amino acid's fate, is very much debatable! Your point of attachment (ligation) is away from both amino and acid functionalities of the amino acid backbone and generating the reacting point on the side chain for different amino acids (your's suggestion-serine) as thioester/boronic acid (vice-versa) is feasible? Better go the Drs. Koehler and El-Emary way!

Grignard reactions will react with an ester from the amino acid, so that would have to be protected as something else (possibly the carboxylate salt).  Grignards may also deprotonate the NH of the amine so a bis protection would be necessary.  Alternatively, zinc reagents can be prepared and are known.  The zinc reagent of iodo-alanine (N-Boc and Me ester) is known in the literature.

Good remarks from Dr. William Harter 

The amino acid entity is retained! The metallation will certainly kick-in the feasible reaction at the side chain ligation point. The serine AA conditions have to be seen!!!

William Harter gave you a great answer. One publication that can be recommended here is: Wan, Kanny K.; Iwasaki, Kotaro; Umotoy, Jeffrey C.; Wolan, Dennis W.; Shenvi, Ryan A.  Angewandte Chemie, International Edition (2015), 54(8), 2410-2415.