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.
Charlie Rich, EV and Renewables FanaticFollowFollowing
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.
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.
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.
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.
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!
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!
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!!!
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.
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.
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!
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.
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.
More
VOTE
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.
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.
More
VOTE
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.
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.
More
VOTE
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!
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!
More
VOTE
Thanks for your valuable suggestion Riaz Khan sir.
Thanks for your valuable suggestion Riaz Khan sir.
More
VOTE
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!!!
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!!!
More
VOTE
The answers provided by Dr. Riaz A. Khan should be taken into consideration.
The answers provided by Dr. Riaz A. Khan should be taken into consideration.
More
VOTE
Good remarks from Dr. William Harter
Good remarks from Dr. William Harter
More
VOTE
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.
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.
More
VOTE
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!
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!
More
VOTE